Nitric oxide, a ubiquitous molecule found throughout the natural world, is a key molecule implicated in many central and benefic molecular pathways and has a well-established role in the function of the central nervous system, as numerous studies have previously shown. Dysregulation of its metabolism, mainly the upregulation of nitric oxide production, has been proposed as a trigger and/or aggravator for many neurological affections. Increasing evidence supports the implication of this molecule in prevalent neurodegenerative diseases, such as Parkinson’s disease, Alzheimer’s disease, or amyotrophic lateral sclerosis. The mechanisms proposed for its neurotoxicity mainly center around the increased quantities of nitric oxide that are produced in the brain, their cause, and, most importantly, the pathological metabolic cascades created. These cascades lead to the formation of neuronal toxic substances that impair the neurons’ function and structure on multiple levels. The purpose of this review is to present the main causes of increased pathological production, as well as the most important pathophysiological mechanisms triggered by nitric oxide, mechanisms that could help explain a part of the complex picture of neurodegenerative diseases and help develop targeted therapies.

Curcumin from Curcuma longa is a nutraceutical compound reported to possess strong antioxidant activity that makes it a candidate for use in counteracting oxidative stress-induced damage. The effect of pre-treatment with curcumin nanoparticles (nC) compared to conventional curcumin (Cs) on blood pressure, electrocardiogram, and biological changes on isoproterenol (ISO)-induced myocardial infarction (MI) in rats had been investigated. The Cs doses of 150 and 200 mg/kg bw and all nC doses (100, 150 and 200 mg/kg bw) significantly reduced heart rate before ISO administration and prevented QRS complex enlargement after MI induction (p < 0.026). All doses of Cs and nC prevented prolongation of the QT and QT corrected (QTc) intervals, with better results for higher doses (p < 0.048). The nC solution had more significant results than Cs in all metabolic parameters assessed (lactate dehydrogenase, glycaemia, aspartate transaminase, and alanine transaminase, p < 0.009). nC was more efficient than Cs in limiting myocardial oxidative stress and enhancing antioxidative capacity (p < 0.004). Compared to Cs, nC better prevented myocardial damage extension, reduced interstitial oedema, and inflammation. Curcumin nanoparticles as compared to conventional curcumin exert better antioxidative effects. Moreover, nC better prevent cardiomyocytes damage, and electrocardiogram alterations, in the case of ISO-induced MI in rats.

We have investigated the cardio-protective effects of pretreatment with curcumin nanoparticles (CUN) compared to conventional curcumin (CUS) on the changes in oxidative stress parameters and inflammatory cytokine levels during induced acute myocardial infarction (AMI) in rats with diabetes mellitus (DM). DM was induced with streptozotocin, and AMI with isoproterenol. Eight groups of seven Wister Bratislava rats were included in the study. The N-C was the normal control group, AMI-C was the group with AMI, DM-C was the group with DM, and DM-AMI-C was the group with DM and AMI. All four groups received saline solution orally during the whole experiment. S-DM-CUS-AMI and S-DM-CUN-AMI groups received saline for seven days prior to DM induction and continued with CUS (200 mg/kg bw, bw = body weight) for S-DM-CUS-AMI and CUN for S-DM-CUN-AMI (200 mg/kg bw) for 15 days before AMI induction. The CUS-DM-CUS-AMI group received CUS (200 mg/kg bw), while the CUN-DM-CUN-AMI received CUN (200 mg/kg bw) for seven days prior to DM induction, and both groups continued with administration in the same doses for 15 days before AMI induction. CUS and CUN prevented elevation of creatine kinase, creatine kinase-MB, lactate dehydrogenase in all groups, with better results in the CUN (S-DM-CUN-AMI and CUN-DM-CUN-AMI groups). CUS and CUN significantly reduced serum levels of oxidative stress markers (malondialdehyde, the indirect assessment of nitric oxide synthesis, and total oxidative status) and enhanced antioxidative markers (total antioxidative capacity and thiols, up to 2.5 times). All groups that received CUS or CUN showed significantly lower serum levels of tumor necrosis factor-alpha, interleukin-6, and interleukin-1β. The best antioxidative and anti-inflammatory effects were obtained for the group that received CUN before DM induction (CUN-DM-CUN-AMI group). Pretreatment with CUN proved higher cardio-protective effects exerting an important antioxidative and anti-inflammatory impact in the case of AMI in DM.

Purpose: Anti-inflammatory proprieties of curcumin were proved to be useful in various diseases, including diabetes mellitus. The aim of this study was to assess the anti-inflammatory comparative effect of curcumin solution with liposomal curcumin formula, regarding the improvement of serum levels of TNF-α (tumor necrosis factor-alpha), IL-6 (interleukin), IL-1α, IL-1β, MCP-1 (monocyte chemoattractant protein-1) and RANTES in experimental diabetes, induced by streptozotocin (STZ), in rats. Materials and methods: Six groups of 7 rats were investigated regarding the effect of i.p. (intraperitoneal) administration of two concentrations of curcumin solution (CC1 and CC2) and two concentrations of liposomal curcumin (LCC1 and LCC2): group 1 – control group with i.p. administration of 1 mL saline solution, group 2 – i.p. STZ administration (60mg/kg bw, bw=body weight), group 3 – STZ+CC1 administration, group 4 – STZ+CC2 administration, group 5 – STZ+ LCC1 administration and group 6 – STZ+ LCC2 administration. The concentrations of curcumin formulas were 1 mg/0.1 kg bw for CC1 and LCC1 and 2 mg/0.1 kg bw for CC2 and LCC2, respectively. Serum levels of C-peptide (as an indicator of pancreatic function) and TNF-α, IL-6, IL-1α, IL-1β, MCP-1, and RANTES (as biomarkers for systemic inflammation) were assessed for each group. Results: The plasma level of C-peptide showed significant improvements when LCC was administrated, with better results for LCC2 when compared to LCC1 (P<0.003). LCC2 pretreatment proved to be more efficient in reducing the level of TNF-α (P<0.003) and RANTES (P<0.003) than CC2 pretreatment. Upon comparing LCC2 with LCC1 formulas, the differences were significant for TNF-α (P=0.004), IL-1β (P=0.022), and RANTES (P=0.003) levels. Conclusion: Liposomal curcumin in a dose of 2 mg/0.1 kg bw proved to have an optimum therapeutic effect as a pretreatment in DM induced by STZ. This result can constitute a base for clinical studies for curcumin efficiency as adjuvant therapy in type 1 DM.

Background: The antioxidant properties of epigallocatechin-gallate (EGCG), a green tea compound, have been already studied in various diseases. Improving the bioavailability of EGCG by nanoformulation may contribute to a more effective treatment of diabetes mellitus (DM) metabolic consequences and vascular complications. The aim of this study was to test the comparative effect of liposomal EGCG with EGCG solution in experimental DM induced by streptozotocin (STZ) in rats. Method: 28 Wistar-Bratislava rats were randomly divided into four groups (7 animals/group): group 1—control group, with intraperitoneal (i.p.) administration of 1 mL saline solution (C); group 2—STZ administration by i.p. route (60 mg/100 g body weight, bw) (STZ); group 3—STZ administration as before + i.p. administration of EGCG solution (EGCG), 2.5 mg/100 g b.w. as pretreatment; group 4—STZ administration as before + i.p. administration of liposomal EGCG, 2.5 mg/100 g b.w. (L-EGCG). The comparative effects of EGCG and L-EGCG were studied on: (i) oxidative stress parameters such as malondialdehyde (MDA), indirect nitric oxide (NOx) synthesis, and total oxidative status (TOS); (ii) antioxidant status assessed by total antioxidant capacity of plasma (TAC), thiols, and catalase; (iii) matrix-metalloproteinase-2 (MMP-2) and -9 (MMP-9). Results: L-EGCG has a better efficiency regarding the improvement of oxidative stress parameters (highly statistically significant with p-values < 0.001 for MDA, NOx, and TOS) and for antioxidant capacity of plasma (highly significant p < 0.001 for thiols and significant for catalase and TAC with p < 0.05). MMP-2 and -9 were also significantly reduced in the L-EGCG-treated group compared with the EGCG group (p < 0.001). Conclusions: the liposomal nanoformulation of EGCG may serve as an adjuvant therapy in DM due to its unique modulatory effect on oxidative stress/antioxidant biomarkers and MMP-2 and -9.

Purpose. The purpose of the current study was to evaluate the long-term functional results based on keratometric measurements, spherical and cylinder equivalent in patients with progressive keratoconus treated with conventional “epi-off” corneal collagen cross-linking (CXL). Methods. We conducted a retrospective study in which 113 eyes from 90 keratoconus-treated patients with CXL between 2006 and 2008 in Oculens Eye Clinic from Cluj-Napoca, Romania, were included. The diagnosis of keratoconus was based on corneal topography and its clinical signs. All patients were evaluated preoperatively, and a follow-up was performed at 1, 3, and 6 months and every year from 1 to 10 years after conventional CXL. Results. All keratometry measurements improved significantly during the follow-up. Compared to preoperative values, the improvement of K_max become statistically significant at 1 year after CXL (mean change compared to baseline −0.9 D, p<0.001) and remained statistically significant thereafter up to 10 years (mean change compared to baseline −2.3 D, p<0.001). As compared to preoperative values, mean spherical equivalent and mean cylinder improved during the follow-up, from a mean of −6.22 D before CXL to a mean value of −5.0 at 10 years, following CXL for spherical equivalent and from −4.4 D at baseline to −3.4 D at 10 years for cylinder (p<0.05 for both). Uncorrected visual acuity increased, remaining statistically significant, by 0.104 logMAR at 10 years after CXL (p=0.0015), and best-corrected visual acuity increased by 0.135 logMAR at 10 years after CXL (p=0.015). We did not observe any case of severe complication. Conclusion. Our results show that CXL has a favorable effect on the progression of KC. The reduced K values, cylinder and spherical equivalent, and increased visual acuity remained the same 10 years after the procedure.