(1) Background: Various epidemiological studies suggest that oxidative stress and disrupted neuronal function are mechanistically linked to neurodegenerative diseases (NDs), including Parkinson’s disease (PD) and Alzheimer’s disease (AD). DNA damage, oxidative stress, lipid peroxidation, and eventually, cell death such as NDs can be induced by nitrosamine-related compounds, leading to neurodegeneration. A limited number of studies have reported that exposure to diethylnitrosamine (DEN), which is commonly found in processed/preserved foods, causes biochemical abnormalities in the brain. Artichoke leaves have been used in traditional medicine as a beneficial source of bioactive components such as hydroxycinnamic acids, cynarine, chlorogenic acid, and flavonoids (luteolin and apigenin). The aim of this study is to investigate the favorable effects of exogenous artichoke (Cynara scolymus) methanolic leaf extract supplementation in ameliorating DEN-induced deleterious effects in BALB/c mouse brains. (2) Methods: This study was designed to evaluate DEN (toxicity induction by 100 mg/kg) and artichoke (protective effects of 0.8 and 1.6 g/kg treatment) for 14 days. All groups underwent a locomotor activity test to evaluate motor activity. In brain tissue, oxidative stress indicators (TAC, TOS, and MDA), Klotho and PPARγ levels, and apoptotic markers (Bax, Bcl-2, and caspase-3) were measured. Brain slices were also examined histopathologically. (3) Results: Artichoke effectively ameliorated DEN-induced toxicity with increasing artichoke dose. Impaired motor function and elevated oxidative stress markers (decreasing MDA and TOS levels and increasing TAC level) induced by DEN intoxication were markedly restored by high-dose artichoke treatment. Artichoke significantly improved the levels of Klotho and PPARγ, which are neuroprotective factors, in mouse brain tissue exposed to DEN. In addition, caspase-3 and Bax levels were reduced, whereas the Bcl-2 level was elevated with artichoke treatment. Furthermore, recovery was confirmed by histopathological analysis. (4) Conclusions: Artichoke exerted neuroprotective effects against DEN-induced brain toxicity by mitigating oxidant parameters and exerting antioxidant and antiapoptotic effects. Further research is needed to fully identify the favorable impact of artichoke supplementation on all aspects of DEN brain intoxication.

During or after chemotherapy, cognitive impairments characterized by forgetfulness, difficulty concentrating, and depressive and anxiety-like symptoms are observed. There is limited research examining the effects of rosuvastatin (RVS), an HMG-CoA reductase inhibitor, in the context of neuroinflammation-related cognitive disruption. Here, we aimed to investigate the neuroprotective potential of RVS against doxorubicin (DOX)-induced cognitive impairments. Experimental groups were planned as control (normal saline, intraperitoneal), DOX (total cumulative dose 10 mg/kg, intraperitoneal), RVS (10 mg/kg, oral, 20 days), and RVS + DOX. Efficacy was monitored by applying a battery of behavioral assessments, as well as biochemical, genetic, histopathological, and immunohistochemical examinations. Results from Morris water maze (MWM), passive avoidance, locomotion activity, and elevated plus maze (EPM) tests showed that DOX administration caused behavioral disorders. Moreover, DOX increased the levels of inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α), while decreasing the levels of interleukin-10 (IL-10), glutathione (GSH), superoxide dismutase, catalase (SOD), endothelial nitric oxide (eNOS), and catalase (CAT). Co-treatment with RSV significantly attenuated DOX-induced behavioral changes and oxidative stress markers. In addition, similar to the immunohistochemical results, we determined that it increased the expression levels of extracellular signal-related kinases 1/2 (ERK1/2), cyclic adenosine monophosphate response element binding protein (CREB), and brain-derived neurotrophic factor (BDNF) and restored the histopathological structure of the brain. Therefore, these results indicated that RSV has a neuroprotective effect against DOX-induced cognitive impairment by reducing neurobehavioral impairments, exerting antioxidant and anti-inflammatory effects, and modulating brain growth factors. Graphical Abstract

Quinic acid (QA) is an alicyclic organic acid widely found in plants. It accumulates in varying concentrations of plant species and is actively metabolized throughout the plant's life cycle. Wound healing after skin injury involves a complex interaction of many cells, fibroblasts, endothelial cells, and regenerated immune cells and their interrelating extracellular matrix. In our study, the healing effect of QA on scar tissue was studied. For this aim, oxidative stress, and changes in FN1 and Collogen1α gene levels were examined. For this purpose, fibroblast cells were seeded in 24, 96 and well plates for wound healing, MTT analysis and Real-Time PCR testing (respectively). Wells were drawn with a 100 µL pipette tip for wound line. As a conclusion of our study, it was determined that cell viability increased significantly, especially in the QA 20 µg-ml group at the end of 48 hours. Increased cell viability and antioxidant capacity resulted in increased cell proliferation. Both FN1 and COL1A1 gene expression levels were up regulated in the QA groups compared to the control group. Our findings show for the first time that quinic acid promotes migration and/or proliferation of fibroblasts by regulating oxidative stress and the FN1A and COL1A1 genes. This activity may be related to the production of FN1A and COL1A1, which are considered important targets for modulation of the tissue repair process.

Introduction: Doxorubicin (DOX) is a potent anti-neoplastic agent widely preferred in treating various tumors. However, DOX’s off-target toxicity in healthy tissues, such as nephrotoxicity, limits its clinical utilization. DOX generates oxidative stress and apoptosis in the kidneys, which stimulates cytotoxic cellular signaling. Myricetin (MYC), an important natural flavonoid, exhibits antioxidant and antiapoptotic features. In this regard, the current report was designed to explore the renoprotective potential of MYC on DOX-induced nephrotoxicity.Methods: Animals were divided into four groups with six rats in each group: control, MYC, DOX, MYC + DOX. MYC was given orally to rats at 100 mg/kg for 10 days and DOX was injected intraperitoneally as a single dose of 20 mg/kg on the eighth day. Serum samples were evaluated for creatinine and blood urea nitrogen (BUN), and histopathological analysis of the kidneys was conducted. The levels of malondialdehyde (MDA), myeloperoxidase (MPO), total oxidant status (TOS), glutathione (GSH), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were measured in the renal tissues. Additionally, biochemical assessments of Bax and Bcl-2 proteins, along with immunohistochemical evaluations of the expression levels of caspase-3 and apoptosis-inducing factor (AIF), were conducted to evaluate apoptosis.Results: Pre-treatment of MYC decreased DOX-elicited elevation in creatinine and BUN levels (p < 0.05). Histopathological findings demonstrated the nephroprotective role of MYC on renal damage (p < 0.05), which was in harmony with the biochemical findings. Furthermore, MYC demonstrated antioxidant properties by reversing the increase in MDA, TOS, and MPO levels and the decrease in GSH, GPx, and TAS levels caused by DOX (p < 0.05). MYC pre-treatment also markedly prohibited DOX-induced elevation of Bax level, and rise of expression of caspase-3 and AIF, and reduction of Bcl-2 levels (p < 0.05).Conclusion: It could be supposed that the nephroprotective role of MYC towards DOX-induced kidney damage might be mediated by its antioxidant and antiapoptotic features.

Background: The medications used to treat cancer can lead to cardiac problems, which restricts their use. Furthermore, the method these medications are taken seems to have an impact on varied out-comes. Therefore, this study aimed to examine whether administering doxorubicin (DOX) agent acutely and chronically has distinct impacts on the electrical activity of the heart. Materials and Methods: Twenty-six male Wistar-Albino rats, weighing between 200-250 grams, were split into three groups: control group; no treatment was applied to animals (n=8), DOX acute group: a single dosage of 15.05 mg/kg of DOX was given at the end of the 3 weeks (n=8), DOX chronic group; which received an intraperitoneal (i.p.) 2.15 mg/kg DOX for 3 weeks, 7 doses in total (n=10). At the end of the experimental period, electrocardiogram (ECG) measurements were taken for all animals and evaluated. Results: ECG data showed that heart rate (HR), P wave amplitude, and P duration did not differ between the acute and control groups but did statistically significantly declined in the chronic group. In both DOX groups, PR interval remained unchanged compared to the control. Also, RR interval increased significantly in the chronic group while it remained unchanged in the acute DOX dose group. The QRS duration was found to have considerably increased in both DOX groups. Furthermore, it was found that both DOX groups had a considerable increase in the QT interval, although the chronic group's increase was more noticeable. Conclusions: In conclusion, it is thought that the ways in which these medications are administered may result in significant variations in heart function. Acute DOX treatment appears to be less harmful than chronic exposure, as evidenced by its lack of adverse effects, particularly on P wave amplitude (a measure of atrial contraction) and P wave duration (the length of the contraction). However, more research is required to validate these findings. Key Words: Electrocardiogram (ECG), Doxorubicin (DOX), Cardiotoxicity

The most malignant type of tumor in the brain is high-grade gliomas. Glioblastoma (GB), a grade 4 glioma, has the lowest 5-year survival rate and is associated with poor prognosis. An important signaling pathway involved in the pathogenesis of GB is the mammalian target of rapamycin (mTOR). Therefore, our study aimed to investigate how exosomes obtained from GB cells applied with different doses of hesperidin (HSP) affect miR- 9 and change the PDK1/AKT/mTOR pathway. For this purpose, T98G cells were treated with different doses (5, 10, 25, and 50 µg/mL) of HSP in combination with temozolomide (TMZ- 10 µg/mL). At the end of 24 h, cell viability, flow cytometry, and biochemical tests were performed. Additionally, exosomes were isolated from cells belonging to the control, TMZ, and high-concentration TMZ-HSP groups. miR- 9, PDK1, PTEN, AKT- 1, Bax, Bcl- 2, and Caspase 3 genes were expressed in both application groups and exosomes belonging to these groups. HSP was found to reduce the viability of GB cells significantly. The viability was significantly reduced, especially in the TMZ-HSP 50 µg/mL group. Depending on the dose, there was a significant increase in the LDH level and oxidative stress level. The apoptosis level was approximately 26% in the TMZ-HSP 50 µg/mL group. Along with all this, gene expressions changed at the exosomal level, and miR- 9 and miR- 146 levels increased. Similarly, it changed the expression of proteins related to the PDK1/AKT/mTOR signaling pathway at the exosomal level ( p < 0.05). In conclusion, the TMZ-HSP combination showed anticancer effects in T98G cells, influenced exosome profiles, and appeared non-toxic and potentially beneficial to healthy cells, highlighting its potential therapeutic value. Graphical Abstract