This page has only limited features, please log in for full access.
The present review focuses on preclinical and clinical studies conducted in the last decade that contribute to increasing knowledge on Coenzyme Q10’s role in health and disease. Classical antioxidant and bioenergetic functions of the coenzyme have been taken into consideration, as well as novel mechanisms of action involving the redox-regulated activation of molecular pathways associated with anti-inflammatory activities. Cardiovascular research and fertility remain major fields of application of Coenzyme Q10, although novel applications, in particular in relation to topical application, are gaining considerable interest. In this respect, bioavailability represents a major challenge and the innovation in formulation aspects is gaining critical importance.
Ilenia Cirilli; Elisabetta Damiani; Phiwayinkosi Vusi Dludla; Iain Hargreaves; Fabio Marcheggiani; Lauren Elizabeth Millichap; Patrick Orlando; Sonia Silvestri; Luca Tiano. Role of Coenzyme Q10 in Health and Disease: An Update on the Last 10 Years (2010–2020). Antioxidants 2021, 10, 1325 .
AMA StyleIlenia Cirilli, Elisabetta Damiani, Phiwayinkosi Vusi Dludla, Iain Hargreaves, Fabio Marcheggiani, Lauren Elizabeth Millichap, Patrick Orlando, Sonia Silvestri, Luca Tiano. Role of Coenzyme Q10 in Health and Disease: An Update on the Last 10 Years (2010–2020). Antioxidants. 2021; 10 (8):1325.
Chicago/Turabian StyleIlenia Cirilli; Elisabetta Damiani; Phiwayinkosi Vusi Dludla; Iain Hargreaves; Fabio Marcheggiani; Lauren Elizabeth Millichap; Patrick Orlando; Sonia Silvestri; Luca Tiano. 2021. "Role of Coenzyme Q10 in Health and Disease: An Update on the Last 10 Years (2010–2020)." Antioxidants 10, no. 8: 1325.
Cadmium is considered the seventh most toxic heavy metal as per ATSDR ranking but its mechanism of toxicity is debated. Recently, we evaluated the effects of this metal on the erythrocyte of teleost fish (Oncorhynchus mykiss) leading us to hypothesize that the pro-oxidant activity of cadmium is not linked to mitochondria but more likely to haemoglobin. In this context, the main aim of this work was to detect the ability of Cd to induce structural perturbation in haemoproteins that present different structures and thus different functional properties and to identify what sites of interaction are mainly involved. The effect of Cd on the structural destabilization of the different haemoproteins was followed spectrophometrically through their precipitation. In addition, the sites of interaction between the different haemoproteins and bivalent cadmium ions were identified by MIB server followed by molecular docking/molecular dynamics simulations both in the dimeric and tetrameric associations. Cadmium does not influence the autoxidation rate of Mb, HbA and trout HbI. However, the presence of this metal accelerates the precipitation process in trout HbIV in a dose-dependent manner. Moreover, the presence of 1−10-50−250-500−1000 μM GSH, a chelating agent, reduces the ability of cadmium to accelerate the denaturation process although it is not able to completely prevent it. In order to explain the experimental results, a computational investigations was carried out to identify the cadmium cation affinity for the studied haemoglobins and myoglobin, both in their dimeric and tetrameric forms. As a result, the highest affinity cadmium binding sites for fish HbIV are located at the interface between tetramer-tetramer association, indicating that the cation can assist supramolecular protein aggregations and induce complex precipitation. For mammalian Hb, Mb and fish HbI computational investigation did not detect any site where Cd could to induce such aggregation, in line with the experimental results. The present study provides new information on the mechanisms of toxicity of cadmium by specific interaction with trout O. mykiss haemoglobin component.
Patrick Orlando; Sonia Silvestri; Ilenia Cirilli; Fabio Marcheggiani; Giancarlo Falcioni; Mattia Cantarini; Roberta Galeazzi; Luca Tiano. Involvement of different hemoprotein thiol groups of Oncorhynchus mykiss in cadmium toxicity. Journal of Trace Elements in Medicine and Biology 2021, 66, 126746 .
AMA StylePatrick Orlando, Sonia Silvestri, Ilenia Cirilli, Fabio Marcheggiani, Giancarlo Falcioni, Mattia Cantarini, Roberta Galeazzi, Luca Tiano. Involvement of different hemoprotein thiol groups of Oncorhynchus mykiss in cadmium toxicity. Journal of Trace Elements in Medicine and Biology. 2021; 66 ():126746.
Chicago/Turabian StylePatrick Orlando; Sonia Silvestri; Ilenia Cirilli; Fabio Marcheggiani; Giancarlo Falcioni; Mattia Cantarini; Roberta Galeazzi; Luca Tiano. 2021. "Involvement of different hemoprotein thiol groups of Oncorhynchus mykiss in cadmium toxicity." Journal of Trace Elements in Medicine and Biology 66, no. : 126746.
Coenzyme Q10 (CoQ10) is an endogenous lipophilic quinone found in equilibrium between its oxidised (ubiquinone) and reduced (ubiquinol) form, ubiquitous in biological membranes and endowed with antioxidant and bioenergetic properties, both crucial to the ageing process. CoQ10 biosynthesis decreases with age in different tissues including skin and its biosynthesis can be modulated by 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors such as statins. Statin-induced CoQ10 deprivation has previously been shown to be associated with the development of a senescence phenotype in cultured human dermal fibroblasts (HDF), hence this model was used to further investigate the role of CoQ10 in skin ageing. The present study aimed to compare the bioavailability of exogenously added CoQ10, in the form of ubiquinone or ubiquinol, to CoQ10-deprived HDF, and to determine their efficacy in rescuing the senescent phenotype induced by CoQ10 deprivation. First, additional senescence markers were implemented to further support the pro-ageing effect of statin-induced CoQ10 deprivation in HDF. Indeed, numerous senescence-associated secretory phenotype (SASP) markers such as p21, IL-8, CXCL1, and MMP-1 were upregulated, whereas components of the extracellular matrix were downregulated (elastin, collagen type 1). Next, we showed that CoQ10 supplementation to statin-treated HDF was able to counteract CoQ10 deprivation and rescued the development of selected senescence/ageing markers in HDF. Ubiquinol resulted more bioavailable than ubiquinone at the same concentration (15 μg/mL) and it significantly improved the cellular oxidative status even within isolated mitochondria highlighting an effective subcellular delivery. Ubiquinol was also more efficient compared to ubiquinone in reverting the expression of the senescent phenotype, quantified in terms of β-galactosidase positivity, p21, collagen type 1, and elastin at the gene and protein expression levels. In conclusion, our results highlight the pivotal role of CoQ10 for skin vitality and strongly support the use of both forms as a beneficial and effective anti-ageing skin care treatment.
Fabio Marcheggiani; Sebastian Kordes; Ilenia Cirilli; Patrick Orlando; Sonia Silvestri; Alexandra Vogelsang; Nadine Möller; Thomas Blatt; Julia M. Weise; Elisabetta Damiani; Luca Tiano. Anti-ageing effects of ubiquinone and ubiquinol in a senescence model of human dermal fibroblasts. Free Radical Biology and Medicine 2021, 165, 282 -288.
AMA StyleFabio Marcheggiani, Sebastian Kordes, Ilenia Cirilli, Patrick Orlando, Sonia Silvestri, Alexandra Vogelsang, Nadine Möller, Thomas Blatt, Julia M. Weise, Elisabetta Damiani, Luca Tiano. Anti-ageing effects of ubiquinone and ubiquinol in a senescence model of human dermal fibroblasts. Free Radical Biology and Medicine. 2021; 165 ():282-288.
Chicago/Turabian StyleFabio Marcheggiani; Sebastian Kordes; Ilenia Cirilli; Patrick Orlando; Sonia Silvestri; Alexandra Vogelsang; Nadine Möller; Thomas Blatt; Julia M. Weise; Elisabetta Damiani; Luca Tiano. 2021. "Anti-ageing effects of ubiquinone and ubiquinol in a senescence model of human dermal fibroblasts." Free Radical Biology and Medicine 165, no. : 282-288.
Impaired adipose tissue function and insulin resistance remain instrumental in promoting hepatic lipid accumulation in conditions of metabolic syndrome. In fact, enhanced lipid accumulation together with oxidative stress and an abnormal inflammatory response underpin the development and severity of non-alcoholic fatty liver disease (NAFLD). There are currently no specific protective drugs against NAFLD, and effective interventions involving regular exercise and healthy diets have proved difficult to achieve and maintain. Alternatively, due to its antioxidant and anti-inflammatory properties, there has been growing interest in understanding the therapeutic effects of N-acetyl cysteine (NAC) against metabolic complications, including NAFLD. Here, reviewed evidence suggests that NAC blocks hepatic lipid accumulation in preclinical models of NAFLD. This is in part through the effective regulation of a fatty acid scavenger molecule (CD36) and transcriptional factors such as sterol regulatory element-binding protein (SREBP)-1c/-2 and peroxisome proliferator-activated receptor gamma (PPARγ). Importantly, NAC appears effective in improving liver function by reducing pro-inflammatory markers such as interleukin (IL)-6 IL-1β, tumour necrosis factor alpha (TNF-α) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). This was primarily through the attenuation of lipid peroxidation and enhancements in intracellular response antioxidants, particularly glutathione. Very few clinical studies support the beneficial effects of NAC against NAFLD-related complications, thus well-organized randomized clinical trials are still necessary to confirm its therapeutic potential.
Phiwayinkosi V. Dludla; Bongani B. Nkambule; Sithandiwe E. Mazibuko-Mbeje; Tawanda M. Nyambuya; Fabio Marcheggiani; Ilenia Cirilli; Khanyisani Ziqubu; Samukelisiwe C. Shabalala; Rabia Johnson; Johan Louw; Elisabetta Damiani; Luca Tiano. N-acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature. Antioxidants 2020, 9, 1283 .
AMA StylePhiwayinkosi V. Dludla, Bongani B. Nkambule, Sithandiwe E. Mazibuko-Mbeje, Tawanda M. Nyambuya, Fabio Marcheggiani, Ilenia Cirilli, Khanyisani Ziqubu, Samukelisiwe C. Shabalala, Rabia Johnson, Johan Louw, Elisabetta Damiani, Luca Tiano. N-acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature. Antioxidants. 2020; 9 (12):1283.
Chicago/Turabian StylePhiwayinkosi V. Dludla; Bongani B. Nkambule; Sithandiwe E. Mazibuko-Mbeje; Tawanda M. Nyambuya; Fabio Marcheggiani; Ilenia Cirilli; Khanyisani Ziqubu; Samukelisiwe C. Shabalala; Rabia Johnson; Johan Louw; Elisabetta Damiani; Luca Tiano. 2020. "N-acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature." Antioxidants 9, no. 12: 1283.
Evidence on the beneficial effects of resveratrol supplementation on cardiovascular disease-related profiles in patients with type 2 diabetes (T2D) is conflicting, while its impact on renal function and blood pressure measurements remains to be established in these patients. The current meta-analysis included randomized controlled trials (RCTs) reporting on the impact of resveratrol supplementation on markers of renal function and blood pressure in patients with T2D on hypoglycemic medication. Electronic databases such as MEDLINE, Cochrane Library, Scopus, and EMBASE were searched for eligible studies from inception up to June 2020. The random and fixed effects model was used in the meta-analysis. A total of five RCTs met the inclusion criteria and involved 388 participants with T2D. Notably, most of the participants were on metformin therapy, or metformin in combination with other hypoglycemic drugs such as insulin and glibenclamide. Pooled estimates showed that resveratrol supplementation in patients with T2D lowered the levels of fasting glucose (SMD: −0.06 [95% CI: −0.24, 0.12]; I2 = 4%, p = 0.39) and insulin (SMD: −0.08 [95% CI: −0.50, 0.34], I2 = 73%, p = 0.002) when compared to those on placebo. In addition, supplementation significantly lowered systolic blood pressure (SMD: −5.77 [95% CI: −8.61, −2.93], I2 = 66%, p = 0.02) in these patients. Although resveratrol supplementation did not affect creatinine or urea levels, it reduced the total protein content (SMD: −0.19 [95% CI: −0.36, −0.02]; I2 = 91%, p = 0.001). In all, resveratrol supplementation in hypoglycemic therapy improves glucose control and lowers blood pressure; however, additional evidence is necessary to confirm its effect on renal function in patients with T2D.
Tawanda M. Nyambuya; Bongani B. Nkambule; Sithandiwe E. Mazibuko-Mbeje; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Patrick Orlando; Sonia Silvestri; Johan Louw; Luca Tiano; Phiwayinkosi V. Dludla. A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy. Molecules 2020, 25, 5645 .
AMA StyleTawanda M. Nyambuya, Bongani B. Nkambule, Sithandiwe E. Mazibuko-Mbeje, Vuyolwethu Mxinwa, Kabelo Mokgalaboni, Patrick Orlando, Sonia Silvestri, Johan Louw, Luca Tiano, Phiwayinkosi V. Dludla. A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy. Molecules. 2020; 25 (23):5645.
Chicago/Turabian StyleTawanda M. Nyambuya; Bongani B. Nkambule; Sithandiwe E. Mazibuko-Mbeje; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Patrick Orlando; Sonia Silvestri; Johan Louw; Luca Tiano; Phiwayinkosi V. Dludla. 2020. "A Meta-Analysis of the Impact of Resveratrol Supplementation on Markers of Renal Function and Blood Pressure in Type 2 Diabetic Patients on Hypoglycemic Therapy." Molecules 25, no. 23: 5645.
Platinum-based compounds are the most widely used anticancer drugs but, their elevated toxicity and chemoresistance has stimulated the study of others, such as ruthenium-based compounds. NAMI-A and UNICAM-1 were tested in vitro, comparing the mechanisms of toxicity, in terms of mitochondrial functionality and cellular oxidative stress. UNICAM-1, showed a clear mitochondrial target and a cytotoxic dose-dependent response thanks to its ability to promote an imbalance of cellular redox status. It impaired directly mitochondrial respiratory chain, promoting mitochondrial superoxide anion production, leading to mitochondrial membrane depolarization. All these aspects, could make UNICAM-1 a valid alternative for chemotherapy treatment of breast cancer.
Sonia Silvestri; Ilenia Cirilli; Fabio Marcheggiani; Phiwayinkosi Dludla; Giulio Lupidi; Riccardo Pettinari; Fabio Marchetti; Corrado Di Nicola; Giancarlo Falcioni; Cristina Marchini; Patrick Orlando; Luca Tiano; Augusto Amici. Evaluation of anticancer role of a novel ruthenium(II)-based compound compared with NAMI-A and cisplatin in impairing mitochondrial functionality and promoting oxidative stress in triple negative breast cancer models. Mitochondrion 2020, 56, 25 -34.
AMA StyleSonia Silvestri, Ilenia Cirilli, Fabio Marcheggiani, Phiwayinkosi Dludla, Giulio Lupidi, Riccardo Pettinari, Fabio Marchetti, Corrado Di Nicola, Giancarlo Falcioni, Cristina Marchini, Patrick Orlando, Luca Tiano, Augusto Amici. Evaluation of anticancer role of a novel ruthenium(II)-based compound compared with NAMI-A and cisplatin in impairing mitochondrial functionality and promoting oxidative stress in triple negative breast cancer models. Mitochondrion. 2020; 56 ():25-34.
Chicago/Turabian StyleSonia Silvestri; Ilenia Cirilli; Fabio Marcheggiani; Phiwayinkosi Dludla; Giulio Lupidi; Riccardo Pettinari; Fabio Marchetti; Corrado Di Nicola; Giancarlo Falcioni; Cristina Marchini; Patrick Orlando; Luca Tiano; Augusto Amici. 2020. "Evaluation of anticancer role of a novel ruthenium(II)-based compound compared with NAMI-A and cisplatin in impairing mitochondrial functionality and promoting oxidative stress in triple negative breast cancer models." Mitochondrion 56, no. : 25-34.
Endothelial dysfunction represents the initial stage in atherosclerotic lesion development which occurs physiologically during aging, but external factors like diet, sedentary lifestyle, smoking accelerate it. Since cigarette smoking promotes oxidative stress and cell damage, we developed an in vitro model of endothelial dysfunction using vascular cells exposed to chemicals present in cigarette smoke, to help elucidate the protective effects of anti-inflammatory and antioxidant agents, such as ubiquinol and vitamin K, that play a fundamental role in vascular health. Treatment of both young and senescent Human Umbilical Vein Endothelial Cells (HUVECs) for 24 h with cigarette smoke extract (CSE) decreased cellular viability, induced apoptosis via reactive oxygen species (ROS) imbalance and mitochondrial dysfunction and promoted an inflammatory response. Moreover, the senescence marker SA-β-galactosidase was observed in both young CSE-exposed and in senescent HUVECs suggesting that CSE exposure accelerates aging in endothelial cells. Supplementation with 10 µM ubiquinol and menaquinone-7 (MK7) counteracted oxidative stress and inflammation, resulting in improved viability, decreased apoptosis and reduced SA-β-galactosidase, but were ineffective against CSE-induced mitochondrial permeability transition pore opening. Other K vitamins tested like menaquinone-4 (MK4) and menaquinone-1 (K1) were less protective. In conclusion, CSE exposure was able to promote a stress-induced senescent phenotype in young endothelial cells likely contributing to endothelial dysfunction in vivo. Furthermore, the molecular changes encountered could be offset by ubiquinol and menaquinone-7 supplementation, the latter resulting the most bioactive K vitamin in counteracting CSE-induced damage.
Ilenia Cirilli; Patrick Orlando; Fabio Marcheggiani; Phiwayinkosi V. Dludla; Sonia Silvestri; Elisabetta Damiani; Luca Tiano. The Protective Role of Bioactive Quinones in Stress-induced Senescence Phenotype of Endothelial Cells Exposed to Cigarette Smoke Extract. Antioxidants 2020, 9, 1008 .
AMA StyleIlenia Cirilli, Patrick Orlando, Fabio Marcheggiani, Phiwayinkosi V. Dludla, Sonia Silvestri, Elisabetta Damiani, Luca Tiano. The Protective Role of Bioactive Quinones in Stress-induced Senescence Phenotype of Endothelial Cells Exposed to Cigarette Smoke Extract. Antioxidants. 2020; 9 (10):1008.
Chicago/Turabian StyleIlenia Cirilli; Patrick Orlando; Fabio Marcheggiani; Phiwayinkosi V. Dludla; Sonia Silvestri; Elisabetta Damiani; Luca Tiano. 2020. "The Protective Role of Bioactive Quinones in Stress-induced Senescence Phenotype of Endothelial Cells Exposed to Cigarette Smoke Extract." Antioxidants 9, no. 10: 1008.
A number of aging-related disorders (ARD) have been related to oxidative stress (OS) and mitochondrial dysfunction (MDF) in a well-established body of literature. Most studies focused on cardiovascular disorders (CVD), type 2 diabetes (T2D), and neurodegenerative disorders. Counteracting OS and MDF has been envisaged to improve the clinical management of ARD, and major roles have been assigned to three mitochondrial cofactors, also termed mitochondrial nutrients (MNs), i.e., α-lipoic acid (ALA), Coenzyme Q10 (CoQ10), and carnitine (CARN). These cofactors exert essential–and distinct—roles in mitochondrial machineries, along with strong antioxidant properties. Clinical trials have mostly relied on the use of only one MN to ARD-affected patients as, e.g., in the case of CoQ10 in CVD, or of ALA in T2D, possibly with the addition of other antioxidants. Only a few clinical and pre-clinical studies reported on the administration of two MNs, with beneficial outcomes, while no available studies reported on the combined administration of three MNs. Based on the literature also from pre-clinical studies, the present review is to recommend the design of clinical trials based on combinations of the three MNs.
Giovanni Pagano; Federico V. Pallardó; Alex Lyakhovich; Luca Tiano; Maria Rosa Fittipaldi; Maria Toscanesi; Marco Trifuoggi. Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures. International Journal of Molecular Sciences 2020, 21, 7060 .
AMA StyleGiovanni Pagano, Federico V. Pallardó, Alex Lyakhovich, Luca Tiano, Maria Rosa Fittipaldi, Maria Toscanesi, Marco Trifuoggi. Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures. International Journal of Molecular Sciences. 2020; 21 (19):7060.
Chicago/Turabian StyleGiovanni Pagano; Federico V. Pallardó; Alex Lyakhovich; Luca Tiano; Maria Rosa Fittipaldi; Maria Toscanesi; Marco Trifuoggi. 2020. "Aging-Related Disorders and Mitochondrial Dysfunction: A Critical Review for Prospect Mitoprotective Strategies Based on Mitochondrial Nutrient Mixtures." International Journal of Molecular Sciences 21, no. 19: 7060.
Epidemiological data show a rise in the mean age of patients affected by heart disease undergoing cardiac surgery. Senescent myocardium reduces the tolerance to ischemic stress and there are indications about age-associated deficit in post-operative cardiac performance. Coenzyme Q10 (CoQ10), and more specifically its reduced form ubiquinol (QH), improve several conditions related to bioenergetic deficit or increased exposure to oxidative stress. This trial (Eudra-CT 2009-015826-13) evaluated the clinical and biochemical effects of ubiquinol in 50 elderly patients affected by severe aortic stenosis undergoing aortic valve replacement and randomized to either placebo or 400 mg/day ubiquinol from 7 days before to 5 days after surgery. Plasma and cardiac tissue CoQ10 levels and oxidative status, circulating troponin I, CK-MB (primary endpoints), IL-6 and S100B were assessed. Moreover, main cardiac adverse effects, NYHA class, contractility and myocardial hypertrophy (secondary endpoints) were evaluated during a 6-month follow-up visit. Ubiquinol treatment counteracted the post-operative plasma CoQ10 decline (p<0.0001) and oxidation (p=0.038) and curbed the post-operative increase in troponin I (QH, 1.90 [1.47-2.48] ng/dL; placebo, 4.03 [2.45-6.63] ng/dL; p=0.007) related to cardiac surgery. Moreover, ubiquinol prevented the adverse outcomes that might have been associated with defective left ventricular ejection fraction recovery in elderly patients.
Patrick Orlando; Jacopo Sabbatinelli; Sonia Silvestri; Fabio Marcheggiani; Ilenia Cirilli; Phiwayinkosi Vusi Dludla; Alberto Molardi; Francesco Nicolini; Luca Tiano. Ubiquinol supplementation in elderly patients undergoing aortic valve replacement: biochemical and clinical aspects. Aging 2020, 12, 15514 -15531.
AMA StylePatrick Orlando, Jacopo Sabbatinelli, Sonia Silvestri, Fabio Marcheggiani, Ilenia Cirilli, Phiwayinkosi Vusi Dludla, Alberto Molardi, Francesco Nicolini, Luca Tiano. Ubiquinol supplementation in elderly patients undergoing aortic valve replacement: biochemical and clinical aspects. Aging. 2020; 12 (15):15514-15531.
Chicago/Turabian StylePatrick Orlando; Jacopo Sabbatinelli; Sonia Silvestri; Fabio Marcheggiani; Ilenia Cirilli; Phiwayinkosi Vusi Dludla; Alberto Molardi; Francesco Nicolini; Luca Tiano. 2020. "Ubiquinol supplementation in elderly patients undergoing aortic valve replacement: biochemical and clinical aspects." Aging 12, no. 15: 15514-15531.
Chronic inflammation and hyperglycaemia are well-established aspects in the pathogenesis of type 2 diabetes mellitus (T2D), including the progression of its associated complications such as cardiovascular diseases (CVDs). In fact, emerging evidence shows that dysfunctional immune responses due to dysregulated T-cell function aggravates CVD-related complications in T2D. However, there is a lack of specific therapeutic interventions that protect patients with diabetes who are at risk of heart failure. Metformin and aspirin are among the leading therapies being used to protect or at the very least slow the progression of CVD-related complications. The current review made use of major electronic databases to identify and systematically synthesise emerging experimental data on the impact of these pharmacological drugs on T-cell responses. The quality and risk of bias of include evidence were independently assessed by two reviewers. Overwhelming evidence showed that both metformin and aspirin can ameliorate T-cell mediated inflammation by inducing regulatory T-cells (Tregs) polarisation, inhibiting T-cell trafficking and activation as well as signal transducer and activator of transcription (STAT)3 signalling. As a plausible mechanism to mediate T-cell function, metformin showed enhanced potential to regulate mechanistic targets of rapamycin (mTOR), STAT5 and adenosine-monophosphate-activated protein kinase (AMPK) signalling pathways. Whilst aspirin modulated nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-kB) and co-stimulatory signalling pathways and induced T-cell anergy. Overall, synthesised data prompt further investigation into the combinational effect of metformin and aspirin for the management of T2D-related cardiovascular complications.
Tawanda Maurice Nyambuya; Phiwayinkosi Vusi Dludla; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Siphamandla Raphael Ngcobo; Luca Tiano; Bongani Brian Nkambule. The impact of metformin and aspirin on T-cell mediated inflammation: A systematic review of in vitro and in vivo findings. Life Sciences 2020, 255, 117854 .
AMA StyleTawanda Maurice Nyambuya, Phiwayinkosi Vusi Dludla, Vuyolwethu Mxinwa, Kabelo Mokgalaboni, Siphamandla Raphael Ngcobo, Luca Tiano, Bongani Brian Nkambule. The impact of metformin and aspirin on T-cell mediated inflammation: A systematic review of in vitro and in vivo findings. Life Sciences. 2020; 255 ():117854.
Chicago/Turabian StyleTawanda Maurice Nyambuya; Phiwayinkosi Vusi Dludla; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Siphamandla Raphael Ngcobo; Luca Tiano; Bongani Brian Nkambule. 2020. "The impact of metformin and aspirin on T-cell mediated inflammation: A systematic review of in vitro and in vivo findings." Life Sciences 255, no. : 117854.
Evidence from randomized controlled trials (RCTs) suggests that coenzyme Q10 (CoQ10) can regulate adipokine levels to impact inflammation and oxidative stress in conditions of metabolic syndrome. Here, prominent electronic databases such as MEDLINE, Cochrane Library, and EMBASE were searched for eligible RCTs reporting on any correlation between adipokine levels and modulation of inflammation and oxidative stress in individuals with metabolic syndrome taking CoQ10. The risk of bias was assessed using the modified Black and Downs checklist, while the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tool was used to evaluate the quality of evidence. Results from the current meta-analysis, involving 318 participants, showed that CoQ10 supplementation in individuals with metabolic syndrome increased adiponectin levels when compared to those on placebo (SMD: 1.44 [95% CI: −0.13, 3.00]; I2 = 96%, p < 0.00001). Moreover, CoQ10 supplementation significantly lowered inflammation markers in individuals with metabolic syndrome in comparison to those on placebo (SMD: −0.31 [95% CI: −0.54, −0.08]; I2 = 51%, p = 0.07). Such benefits with CoQ10 supplementation were related to its ameliorative effects on lipid peroxidation by reducing malondialdehyde levels, concomitant to improving glucose control and liver function. The overall findings suggest that optimal regulation of adipokine function is crucial for the beneficial effects of CoQ10 in improving metabolic health.
Phiwayinkosi V. Dludla; Patrick Orlando; Sonia Silvestri; Fabio Marcheggiani; Ilenia Cirilli; Tawanda M. Nyambuya; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Bongani B. Nkambule; Rabia Johnson; Sithandiwe E. Mazibuko-Mbeje; Christo J. F. Muller; Johan Louw; Luca Tiano. Coenzyme Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials. International Journal of Molecular Sciences 2020, 21, 3247 .
AMA StylePhiwayinkosi V. Dludla, Patrick Orlando, Sonia Silvestri, Fabio Marcheggiani, Ilenia Cirilli, Tawanda M. Nyambuya, Vuyolwethu Mxinwa, Kabelo Mokgalaboni, Bongani B. Nkambule, Rabia Johnson, Sithandiwe E. Mazibuko-Mbeje, Christo J. F. Muller, Johan Louw, Luca Tiano. Coenzyme Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials. International Journal of Molecular Sciences. 2020; 21 (9):3247.
Chicago/Turabian StylePhiwayinkosi V. Dludla; Patrick Orlando; Sonia Silvestri; Fabio Marcheggiani; Ilenia Cirilli; Tawanda M. Nyambuya; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Bongani B. Nkambule; Rabia Johnson; Sithandiwe E. Mazibuko-Mbeje; Christo J. F. Muller; Johan Louw; Luca Tiano. 2020. "Coenzyme Q10 Supplementation Improves Adipokine Levels and Alleviates Inflammation and Lipid Peroxidation in Conditions of Metabolic Syndrome: A Meta-Analysis of Randomized Controlled Trials." International Journal of Molecular Sciences 21, no. 9: 3247.
Recent evidence shows that rooibos compounds, aspalathin and phenylpyruvic acid-2-O-β-d-glucoside (PPAG), can independently protect cardiomyocytes from hyperglycemia-related reactive oxygen species (ROS). While aspalathin shows more potency by enhancing intracellular antioxidant defenses, PPAG acts more as an anti-apoptotic agent. Thus, to further understand the protective capabilities of these compounds against hyperglycemia-induced cardiac damage, their combinatory effect was investigated and compared to metformin. An in vitro model of H9c2 cardiomyocytes exposed to chronic glucose concentrations was employed to study the impact of such compounds on hyperglycemia-induced damage. Here, high glucose exposure impaired myocardial substrate utilization by abnormally enhancing free fatty acid oxidation while concomitantly suppressing glucose oxidation. This was paralleled by altered expression of genes involved in energy metabolism including acetyl-CoA carboxylase (ACC), 5′ AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor-alpha (PPARα). The combination treatment improved myocardial substrate metabolism, maintained mitochondrial membrane potential, and attenuated various markers for oxidative stress including nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and glutathione content. It also showed a much-improved effect by ameliorating DNA damage when compared to metformin. The current study demonstrates that rooibos compounds offer unique cardioprotective properties against hyperglycemia-induced and potentially against diabetes-induced cardiac damage. These data also support further exploration of rooibos compounds to better assess the cardioprotective effects of different bioactive compound combinations.
Phiwayinkosi V. Dludla; Christo J. F. Muller; Johan Louw; Sithandiwe E. Mazibuko-Mbeje; Luca Tiano; Sonia Silvestri; Patrick Orlando; Fabio Marcheggiani; Ilenia Cirilli; Nireshni Chellan; Samira Ghoor; Bongani B. Nkambule; M. Faadiel Essop; Barbara Huisamen; Rabia Johnson. The Combination Effect of Aspalathin and Phenylpyruvic Acid-2-O-β-d-glucoside from Rooibos against Hyperglycemia-Induced Cardiac Damage: An In Vitro Study. Nutrients 2020, 12, 1151 .
AMA StylePhiwayinkosi V. Dludla, Christo J. F. Muller, Johan Louw, Sithandiwe E. Mazibuko-Mbeje, Luca Tiano, Sonia Silvestri, Patrick Orlando, Fabio Marcheggiani, Ilenia Cirilli, Nireshni Chellan, Samira Ghoor, Bongani B. Nkambule, M. Faadiel Essop, Barbara Huisamen, Rabia Johnson. The Combination Effect of Aspalathin and Phenylpyruvic Acid-2-O-β-d-glucoside from Rooibos against Hyperglycemia-Induced Cardiac Damage: An In Vitro Study. Nutrients. 2020; 12 (4):1151.
Chicago/Turabian StylePhiwayinkosi V. Dludla; Christo J. F. Muller; Johan Louw; Sithandiwe E. Mazibuko-Mbeje; Luca Tiano; Sonia Silvestri; Patrick Orlando; Fabio Marcheggiani; Ilenia Cirilli; Nireshni Chellan; Samira Ghoor; Bongani B. Nkambule; M. Faadiel Essop; Barbara Huisamen; Rabia Johnson. 2020. "The Combination Effect of Aspalathin and Phenylpyruvic Acid-2-O-β-d-glucoside from Rooibos against Hyperglycemia-Induced Cardiac Damage: An In Vitro Study." Nutrients 12, no. 4: 1151.
In this randomized, double-blind, single-center trial (ANZCTR number ACTRN12619000436178) we aimed to investigate changes in endothelium-dependent vasodilation induced by ubiquinol, the reduced form of coenzyme Q10 (CoQ10), in healthy subjects with moderate dyslipidemia. Fifty-one subjects with low-density lipoprotein (LDL) cholesterol levels of 130–200 mg/dL, not taking statins or other lipid lowering treatments, moderate (2.5%–6.0%) endothelial dysfunction as measured by flow-mediated dilation (FMD) of the brachial artery, and no clinical signs of cardiovascular disease were randomized to receive either ubiquinol (200 or 100 mg/day) or placebo for 8 weeks. The primary outcome measure was the effect of ubiquinol supplementation on FMD at the end of the study. Secondary outcomes included changes in FMD on week 4, changes in total and oxidized plasma CoQ10 on week 4 and week 8, and changes in serum nitrate and nitrite levels (NOx), and plasma LDL susceptibility to oxidation in vitro on week 8. Analysis of the data of the 48 participants who completed the study demonstrated a significantly increased FMD in both treated groups compared with the placebo group (200 mg/day, +1.28% ± 0.90%; 100 mg/day, +1.34% ± 1.44%; p < 0.001) and a marked increase in plasma CoQ10, either total (p < 0.001) and reduced (p < 0.001). Serum NOx increased significantly and dose-dependently in all treated subjects (p = 0.016), while LDL oxidation lag time improved significantly in those receiving 200 mg/day (p = 0.017). Ubiquinol significantly ameliorated dyslipidemia-related endothelial dysfunction. This effect was strongly related to increased nitric oxide bioavailability and was partly mediated by enhanced LDL antioxidant protection.
Jacopo Sabbatinelli; Patrick Orlando; Roberta Galeazzi; Sonia Silvestri; Ilenia Cirilli; Fabio Marcheggiani; Phiwayinkosi V. Dludla; Angelica Giuliani; Anna Rita Bonfigli; Laura Mazzanti; Fabiola Olivieri; Roberto Antonicelli; Luca Tiano. Ubiquinol Ameliorates Endothelial Dysfunction in Subjects with Mild-to-Moderate Dyslipidemia: A Randomized Clinical Trial. Nutrients 2020, 12, 1098 .
AMA StyleJacopo Sabbatinelli, Patrick Orlando, Roberta Galeazzi, Sonia Silvestri, Ilenia Cirilli, Fabio Marcheggiani, Phiwayinkosi V. Dludla, Angelica Giuliani, Anna Rita Bonfigli, Laura Mazzanti, Fabiola Olivieri, Roberto Antonicelli, Luca Tiano. Ubiquinol Ameliorates Endothelial Dysfunction in Subjects with Mild-to-Moderate Dyslipidemia: A Randomized Clinical Trial. Nutrients. 2020; 12 (4):1098.
Chicago/Turabian StyleJacopo Sabbatinelli; Patrick Orlando; Roberta Galeazzi; Sonia Silvestri; Ilenia Cirilli; Fabio Marcheggiani; Phiwayinkosi V. Dludla; Angelica Giuliani; Anna Rita Bonfigli; Laura Mazzanti; Fabiola Olivieri; Roberto Antonicelli; Luca Tiano. 2020. "Ubiquinol Ameliorates Endothelial Dysfunction in Subjects with Mild-to-Moderate Dyslipidemia: A Randomized Clinical Trial." Nutrients 12, no. 4: 1098.
The current study explored the effect of isoorientin on the metabolic activity and lipid accumulation in fully differentiated 3T3-L1 adipocytes. To achieve this, the 3T3-L1 pre-adipocytes were differentiated for eight days and treated with various concentrations of isoorientin (0.1–100 μM) for four hours. Subsequently, the metabolic activity, lipid accumulation, and mitochondrial respiration were assessed. Furthermore, to unravel the molecular mechanisms that might elucidate the bioactivity of isoorientin, protein expression of the genes involved in insulin signaling and energy expenditure, such as AKT and AMPK, were investigated. The results showed that isoorientin, at different doses, could block lipid storage and enhance glycerol release, with a concomitant improvement of the metabolic activity and mitochondrial function. Although the observed beneficial effects of isoorientin on these cultured 3T3-L1 adipocytes were not consistent at all concentrations, it was clear that doses between 1 and 10 μM were most effective compared to the untreated control. Moreover, the activity of isoorientin was comparable to tested positive controls of CL-316,2431, isoproterenol, insulin, and metformin. Mechanistically, protein expression of AKT and AMPK, was enhanced with isoorientin exposure, suggesting their partial role in modulating lipid metabolism and mitochondrial biogenesis. Indeed, our results showed that isoorientin has the ability to enhance mitochondrial respiration, as we observed an increase in the ATP and oxygen consumption rate. Therefore, we concluded that isoorientin has a potential to impact mitochondrial activity, lipid metabolism and energy expenditure using an in vitro experimental model of obesity.
Khanyisani Ziqubu; Christo J. F. Muller; Phiwayinkosi V. Dludla; Sinenhlanhla X. H. Mthembu; Nnini Obonye; Johan Louw; Abidemi P. Kappo; Sonia Silvestri; Patrick Orlando; Luca Tiano; Sithandiwe E. Mazibuko-Mbeje. Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes. Molecules 2020, 25, 1773 .
AMA StyleKhanyisani Ziqubu, Christo J. F. Muller, Phiwayinkosi V. Dludla, Sinenhlanhla X. H. Mthembu, Nnini Obonye, Johan Louw, Abidemi P. Kappo, Sonia Silvestri, Patrick Orlando, Luca Tiano, Sithandiwe E. Mazibuko-Mbeje. Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes. Molecules. 2020; 25 (8):1773.
Chicago/Turabian StyleKhanyisani Ziqubu; Christo J. F. Muller; Phiwayinkosi V. Dludla; Sinenhlanhla X. H. Mthembu; Nnini Obonye; Johan Louw; Abidemi P. Kappo; Sonia Silvestri; Patrick Orlando; Luca Tiano; Sithandiwe E. Mazibuko-Mbeje. 2020. "Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes." Molecules 25, no. 8: 1773.
Scientific research has been underway for decades in order to develop an effective anticancer drug, and it has become crucial to find a novel and effective chemotherapeutics in the case of prostate cancer treatment. Ebselen derivatives have been shown to possess a variety of biological activities, including cytostatic and cytotoxic action against tumor cells. In this study, the cytotoxic effect and anticancer mechanism of action of two organoselenium compounds— (N-allyl-1,2-benzisoselenazol-3(2H)-one (N-allyl-BS) and N-(3-methylbutyl)-1,2-benzisoselenazol-3(2H)-one) (N-(3-mb)-BS)—were investigated on two phenotypically different prostate cancer cell lines DU 145 and PC-3. The influence of analyzed compounds on the viability parameter was also assessed on normal prostate cell line PNT1A. The results showed that both organoselenium compounds (OSCs) efficiently inhibited cancer cell proliferation, whereas normal PNT1A cells were less sensitive to the analazyed ebselen analouges. Both OSCs induced G2/M cell cycle arrest and prompted cell death through apoptosis. The detection of cleaved Poly (ADP-ribose) Polymerase (PARP) confirmed this. In addition, N-allyl-BS and N-(3-m)-b-BS increased the level of reactive oxygen species (ROS) formation, however only N-allyl-BS induced DNA damage. Based on our data, we assume that OSCs’ anticancer action can be associated with oxidative stress induction and inactivation of the Akt- dependent signalling pathway. In conclusion, our data demonstrate that ebselen derivatives showed strong cytotoxic efficiency towards prostate cancer cells and may be elucidated as a novel, potent anticancer agent.
Katarzyna B. Kaczor-Keller; Anna Pawlik; Jacek Scianowski; Agata Pacuła; Magdalena Obieziurska; Fabio Marcheggiani; Ilenia Cirilli; Luca Tiano; Jedrzej Antosiewicz. In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues. Pharmaceuticals 2020, 13, 47 .
AMA StyleKatarzyna B. Kaczor-Keller, Anna Pawlik, Jacek Scianowski, Agata Pacuła, Magdalena Obieziurska, Fabio Marcheggiani, Ilenia Cirilli, Luca Tiano, Jedrzej Antosiewicz. In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues. Pharmaceuticals. 2020; 13 (3):47.
Chicago/Turabian StyleKatarzyna B. Kaczor-Keller; Anna Pawlik; Jacek Scianowski; Agata Pacuła; Magdalena Obieziurska; Fabio Marcheggiani; Ilenia Cirilli; Luca Tiano; Jedrzej Antosiewicz. 2020. "In Vitro Anti-Prostate Cancer Activity of Two Ebselen Analogues." Pharmaceuticals 13, no. 3: 47.
Aims Coenzyme Q10 (CoQ10) is well known for its beneficial effects in cardiovascular disease (CVD); however, reported evidence has not been precisely synthesized to better inform on its impact in protecting against cardiovascular‐related complications in diabetic patients. Materials and Methodology The current meta‐analysis included randomized controlled trials published in the past 5 years reporting on the effect of CoQ10 on metabolic and CVD‐related risk profiles in individuals with diabetes or metabolic syndrome. We searched electronic databases such as MEDLINE, Cochrane Library, Scopus and EMBASE for eligible studies. In addition to assessing the risk of bias and quality of evidence, the random and fixed‐effect models were used to calculate the standardized mean difference and 95% confidence intervals for metabolic parameters and CVD outcomes. Results Overall, 12 studies met the inclusion criteria, enrolling a total of 650 patients. Although CoQ10 supplementation did not statistically affect all metabolic profiles measured, it significantly reduced CVD‐risk‐related indexes such as total cholesterol and low‐density lipoprotein (LDL) levels in diabetic patients when compared to those on placebo [SMD = 0.13, 95% CI (0.03; 0.23), Chi2 = 43.62 and I2 = 29%, P = .07]. Conclusions The overall results demonstrated that supplementation with CoQ10 shows an enhanced potential to lower CVD risk in diabetic patients by reducing total cholesterol and LDL. Moreover, the beneficial effects of CoQ10 in lowering the CVD risk are associated with its ameliorative properties against oxidative stress and improving endothelial health.
Phiwayinkosi V. Dludla; Tawanda M. Nyambuya; Patrick Orlando; Sonia Silvestri; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Bongani B. Nkambule; Johan Louw; Christo J. F. Muller; Luca Tiano. The impact of coenzyme Q 10 on metabolic and cardiovascular disease profiles in diabetic patients: A systematic review and meta‐analysis of randomized controlled trials. Endocrinology, Diabetes & Metabolism 2020, 3, e00118 .
AMA StylePhiwayinkosi V. Dludla, Tawanda M. Nyambuya, Patrick Orlando, Sonia Silvestri, Vuyolwethu Mxinwa, Kabelo Mokgalaboni, Bongani B. Nkambule, Johan Louw, Christo J. F. Muller, Luca Tiano. The impact of coenzyme Q 10 on metabolic and cardiovascular disease profiles in diabetic patients: A systematic review and meta‐analysis of randomized controlled trials. Endocrinology, Diabetes & Metabolism. 2020; 3 (2):e00118.
Chicago/Turabian StylePhiwayinkosi V. Dludla; Tawanda M. Nyambuya; Patrick Orlando; Sonia Silvestri; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Bongani B. Nkambule; Johan Louw; Christo J. F. Muller; Luca Tiano. 2020. "The impact of coenzyme Q 10 on metabolic and cardiovascular disease profiles in diabetic patients: A systematic review and meta‐analysis of randomized controlled trials." Endocrinology, Diabetes & Metabolism 3, no. 2: e00118.
Food-derived bioactive compounds such as resveratrol are increasingly explored for their protective effects against metabolic complications. Evidence supports the strong antioxidant properties and therapeutic effects of resveratrol in managing diabetes and its associated complications. However, evidence informing on the comparative or combination effects of this natural compound with an accomplished and well-characterized antidiabetic agent like metformin has not been revised. Thus, we conducted a comprehensive systematic search of the major electronic databases which included MEDLINE, Cochrane Library, and EMBASE. The cumulative evidence strongly supports the comparative effects of metformin and resveratrol in ameliorating diabetes-associated complications in preclinical settings. In particular, both compounds showed strong ameliorative effects against hyperglycemia, dyslipidemia, insulin resistance, a pro-inflammatory response, and lipid peroxidation in various experimental models of diabetes. Enhancing intracellular antioxidant capacity in addition to activating NAD-dependent deacetylase sirtuin-1 (SIRT1) and AMP-activated protein kinase (AMPK) are the prime mechanisms involved in the therapeutic effects of these compounds. Of interest, preclinical evidence also demonstrates that the combination treatment with these compounds may have a greater efficacy in protecting against diabetes. Thus, confirmation of such evidence in well-organized clinical trials remains crucial to uncover novel therapeutic strategies to manage diabetes and its linked complications.
Phiwayinkosi V. Dludla; Sonia Silvestri; Patrick Orlando; Kwazi B. Gabuza; Sithandiwe E. Mazibuko-Mbeje; Tawanda M. Nyambuya; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Rabia Johnson; Christo J. F. Muller; Luca Tiano; Johan Louw; Bongani B. Nkambule. Exploring the Comparative Efficacy of Metformin and Resveratrol in the Management of Diabetes-Associated Complications: A Systematic Review of Preclinical Studies. Nutrients 2020, 12, 739 .
AMA StylePhiwayinkosi V. Dludla, Sonia Silvestri, Patrick Orlando, Kwazi B. Gabuza, Sithandiwe E. Mazibuko-Mbeje, Tawanda M. Nyambuya, Vuyolwethu Mxinwa, Kabelo Mokgalaboni, Rabia Johnson, Christo J. F. Muller, Luca Tiano, Johan Louw, Bongani B. Nkambule. Exploring the Comparative Efficacy of Metformin and Resveratrol in the Management of Diabetes-Associated Complications: A Systematic Review of Preclinical Studies. Nutrients. 2020; 12 (3):739.
Chicago/Turabian StylePhiwayinkosi V. Dludla; Sonia Silvestri; Patrick Orlando; Kwazi B. Gabuza; Sithandiwe E. Mazibuko-Mbeje; Tawanda M. Nyambuya; Vuyolwethu Mxinwa; Kabelo Mokgalaboni; Rabia Johnson; Christo J. F. Muller; Luca Tiano; Johan Louw; Bongani B. Nkambule. 2020. "Exploring the Comparative Efficacy of Metformin and Resveratrol in the Management of Diabetes-Associated Complications: A Systematic Review of Preclinical Studies." Nutrients 12, no. 3: 739.
To evaluate T-helper cytokine responses in a short-term high fat diet (HFD) induced impaired glucose metabolism. To further evaluate the modulation of T-helper 1 (Th1) and T-helper 2 (Th2) cytokines using short-term low-dose aspirin in combination with metformin. Two experiments were carried out in this study in order to evaluate the T-helper cytokine profiles in a state of impaired glucose metabolism. A total of 28 six-week-old male C57BL/6 mice were used in this study. In the first experiment, mice were fed either a high fat diet or low fat diet for a duration of 10 weeks. We then determined the Th1, Th2 and T-helper 17 (Th17) cytokine profiles. In the second experiment, we evaluated whether the short term 6-week treatment with low-dose aspirin in combination with metformin modulates T-helper cytokine profiles of the HFD-fed mice. In the first experiment, we measured the body weights, blood glucose levels, insulin levels, lipid profiles and haematological parameters. We further performed oral glucose tolerance testing following an 8-hour fast and serum Th1, Th2 and Th17 cytokine levels were also determined following short-term 8-week diet-feeding and 6-week low-dose aspirin and combined metformin with low-dose aspirin treatment. High fat diet-feeding caused a marked increase in circulating peripheral blood lymphocytes, which was attenuated by short-term low-dose aspirin treatment. Moreover, the HFD feeding resulted in 2-fold increase in total cholesterol and a 4-fold increase in low-density lipoprotein cholesterol when compared to the low-fat diet-fed group (p < 0.05). In the high fat diet group, impaired glucose metabolism was associated with skewed Th2 responses without alterations in the Th1 and Th17 cytokine profiles. Interestingly the short-term treatment with low-dose aspirin showed no effect on the selected T-helper 1 cytokine IFN-Ƴ (P > 0.05). While the combination of low-dose aspirin with metformin considerably reduced the levels of serum IFN-Ƴ (P < 0.05). Furthermore low-dose aspirin treatment showed the modest attenuation of the selected Th2 cytokines, IL-10 and IL-13 when compared to low-dose aspirin with metformin (P < 0.01). The early immunological and metabolic changes that occur in a state impaired glucose tolerance are accompanied by the increased production of Th2 cell cytokines. The short-term treatment using low-dose aspirin combined with metformin may provide therapeutic benefits in preventing complications associated with dysregulated Th2 cell responses.
Thabsile J. Mahlangu; Phiwayinkosi V. Dludla; Vuyolwethu Mxinwa; Zibusiso Mkandla; Luca Tiano; Johan Louw; Tinashe Mutize; Tawanda Maurice Nyambuya; Bongani B Nkambule. Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin. Cytokine 2020, 128, 154999 .
AMA StyleThabsile J. Mahlangu, Phiwayinkosi V. Dludla, Vuyolwethu Mxinwa, Zibusiso Mkandla, Luca Tiano, Johan Louw, Tinashe Mutize, Tawanda Maurice Nyambuya, Bongani B Nkambule. Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin. Cytokine. 2020; 128 ():154999.
Chicago/Turabian StyleThabsile J. Mahlangu; Phiwayinkosi V. Dludla; Vuyolwethu Mxinwa; Zibusiso Mkandla; Luca Tiano; Johan Louw; Tinashe Mutize; Tawanda Maurice Nyambuya; Bongani B Nkambule. 2020. "Elevated T-helper 2 cytokine levels in high fat diet-fed C57BL/6 mice are attenuated by short-term 6-week treatment with a combination of low-dose aspirin and metformin." Cytokine 128, no. : 154999.
The T-helper (Th1/Th2) paradigm is widely studied for its role in modulating an adaptive immune response, especially in relation to the onset of various autoimmune diseases. In fact, emerging evidence clearly shows an inverse relationship between Th1/Th2 cytokines and the development of type 2 diabetes (T2D) complications, which is accelerated by an exacerbated inflammatory state. Here, relevant studies reporting on any association between the levels of Th1/Th2 cytokines and the development of T2D were retrieved through major electronic databases such as The Cochrane Library, Embase and PubMed. Extracted evidence which mostly involved animal models and human subjects with T2D or metabolic syndrome was assessed for quality and risk of bias using the Downs and Black checklist and Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines. Results strongly correlated raised Th1/Th2 cytokines such as interferon-gamma (IFN-γ)/interleukin (IL)-5 and IL-2/IL-5 ratios to T2D, and this was positively linked with the other complications including retinopathy and cardiovascular complications. Further, logistic regression analysis demonstrated that the Th1/Th2 ratios were significantly associated with impaired glucose homeostasis, abnormally enhanced lipid profiles, and insulin resistance. Although more studies making use of a larger sample size are required, current data suggest that optimal modulation of Th1/Th2 cytokines may be an important aspect in the management of T2D and its associated complications.
Thabsile Mahlangu; Phiwayinkosi V. Dludla; Tawanda M. Nyambuya; Vuyolwethu Mxinwa; Sithandiwe E. Mazibuko-Mbeje; Ilenia Cirilli; Fabio Marcheggiani; Luca Tiano; Johan Louw; Bongani B. Nkambule. A systematic review on the functional role of Th1/Th2 cytokines in type 2 diabetes and related metabolic complications. Cytokine 2019, 126, 154892 .
AMA StyleThabsile Mahlangu, Phiwayinkosi V. Dludla, Tawanda M. Nyambuya, Vuyolwethu Mxinwa, Sithandiwe E. Mazibuko-Mbeje, Ilenia Cirilli, Fabio Marcheggiani, Luca Tiano, Johan Louw, Bongani B. Nkambule. A systematic review on the functional role of Th1/Th2 cytokines in type 2 diabetes and related metabolic complications. Cytokine. 2019; 126 ():154892.
Chicago/Turabian StyleThabsile Mahlangu; Phiwayinkosi V. Dludla; Tawanda M. Nyambuya; Vuyolwethu Mxinwa; Sithandiwe E. Mazibuko-Mbeje; Ilenia Cirilli; Fabio Marcheggiani; Luca Tiano; Johan Louw; Bongani B. Nkambule. 2019. "A systematic review on the functional role of Th1/Th2 cytokines in type 2 diabetes and related metabolic complications." Cytokine 126, no. : 154892.
Impaired mitochondrial function concomitant to enhanced oxidative stress-induced damage are well established mechanisms involved in hyperlipidemia-induced cardiotoxicity. Coenzyme Q9/10 (CoQ) is known to be a critical component of the mitochondrial electron transport chain that efficiently supports the process of bioenergetics in addition to its antioxidant activities. However, there is very limited information on the direct effect of myocardial lipid overload on endogenous CoQ levels in association with mitochondrial respiration and oxidative stress status. Here, such effects were explored by exposing H9c2 cardiomyocytes to various doses (0.15 to 1 mM) of palmitate for 24 hours. The results demonstrated that palmitate doses ≥ 0.25 mM are enough to impair mitochondrial respiration and cause oxidative stress. Although endogenous CoQ levels are enhanced by palmitate doses ≤ 5 mM, this is not enough to counteract oxidative stress, but is sufficient to maintain cell viability of cardiomyocytes, suggesting a compensation mechanism. Palmitate doses > 5 mM caused severe mitochondrial toxicity, including reduction of cell viability. Interestingly, enhancement of CoQ levels with the lowest dose of palmitate (0.15 mM) was accompanied by a significantly reduction of CoQ oxidation status, as well as low cytosolic production of reactive oxygen species. From the overall findings, it appears that CoQ response may be crucial to improve mitochondrial function and thus protect against hyperlipidemia-induced insult. These results further suggest that therapeutic agents that can stimulate endogenous levels of CoQ may be beneficial in protecting the myocardium against diabetes associated complications.
Phiwayinkosi V. Dludla; Sonia Silvestri; Patrick Orlando; Sithandiwe E. Mazibuko-Mbeje; Rabia Johnson; Fabio Marcheggiani; Ilenia Cirilli; Christo J.F. Muller; Johan Louw; Nireshni Chellan; Nnini Obonye; Bongani B. Nkambule; Luca Tiano. Palmitate-induced toxicity is associated with impaired mitochondrial respiration and accelerated oxidative stress in cultured cardiomyocytes: the critical role of Coenzyme Q9/10. 2019, 830331 .
AMA StylePhiwayinkosi V. Dludla, Sonia Silvestri, Patrick Orlando, Sithandiwe E. Mazibuko-Mbeje, Rabia Johnson, Fabio Marcheggiani, Ilenia Cirilli, Christo J.F. Muller, Johan Louw, Nireshni Chellan, Nnini Obonye, Bongani B. Nkambule, Luca Tiano. Palmitate-induced toxicity is associated with impaired mitochondrial respiration and accelerated oxidative stress in cultured cardiomyocytes: the critical role of Coenzyme Q9/10. . 2019; ():830331.
Chicago/Turabian StylePhiwayinkosi V. Dludla; Sonia Silvestri; Patrick Orlando; Sithandiwe E. Mazibuko-Mbeje; Rabia Johnson; Fabio Marcheggiani; Ilenia Cirilli; Christo J.F. Muller; Johan Louw; Nireshni Chellan; Nnini Obonye; Bongani B. Nkambule; Luca Tiano. 2019. "Palmitate-induced toxicity is associated with impaired mitochondrial respiration and accelerated oxidative stress in cultured cardiomyocytes: the critical role of Coenzyme Q9/10." , no. : 830331.