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One of the most often utilized nanoparticles (NPs) in several technologies is zinc oxide (ZnO) NPs. However, these NPs are said to have harmful effects on the reproductive system. Thus, we designed this study to specify the potential preventive activity of vitamins (Vits) A, C, and E, as antioxidants, against toxicity of ZnO NPs in the testes of rats. A total of 54 Wistar rats were arranged in 9 groups of 6 and then orally received water (control 1), olive oil (control 2), Vit A (1000 IU/kg), Vit C (200 mg/kg), Vit E (100 IU/kg), ZnO (200 mg/kg), ZnO+Vit A, ZnO+Vit C, and ZnO+Vit E. To determine the amount of testicular injury, sperm analysis and histological evaluation were performed. In addition, oxidative stress status was examined using colorimetric and qRT-PCR methods. Our findings suggest that ZnO NPs cause adverse effects on sperm parameters and testicular histology. Furthermore, oxidative biomarkers (malondialdehyde and total oxidant capacity) were enhanced in the ZnO group. By contrast, the gene expression and activities of antioxidant enzymes (SOD, GPx, and CAT) noted a remarkable decrease in the ZnO group regarding control (p < 0.05). However, oxidative markers were remarkably mitigated after combined treatment of ZnO NPs and Vits A, C, or E compared to the rats given ZnO NPs (p < 0.05). Additionally, compared to the ZnO NP group, the rats receiving Vits+ZnO NPs exhibit increased antioxidant enzyme activity and mRNA expression (p < 0.05). The findings demonstrate the abovementioned Vits' ameliorative effects on toxicity incurred by ZnO NPs. [ABSTRACT FROM AUTHOR]

Background. Kirsten rat sarcoma (KRAS) protein is an essential contributor to the development of pancreatic ductal adenocarcinoma (PDAC). KRAS G12D and G12V mutant tumours are significant challenges in cancer therapy due to high resistance to the treatment. Objective. To determine how effective is the ATO/D-VC combination in suppression of PDAC the mouse transgenic model. This study investigated the antitumour effect of a novel combination of arsenic trioxide (ATO) and D-ascorbic acid isomer (D-VC). Such a combination can be used to treat KRAS mutant cancer by inducing catastrophic oxidative stress. Methods. In this study, we examined the effectiveness of ATO and D-VC on xenograft models—AK192 cells transplanted into mice. Previously, it has been shown that a high concentration of Vitamin C (VC) selectively can kill the cells expressing KRAS. Results. The results of this study demonstrated that the combination of VC with a low dose of the oxidizing drug ATO led to the enhancement of the therapeutic effect. These findings suggest that the combined treatment using ATO and D-VC is a promising approach to overcome the limitation of drug selectivity and efficacy. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury (DILI) is the main cause of liver damage mediated by the excretion of toxic active drug metabolites. Omega-3 fatty acids and vitamin C have potent antioxidant, anti-inflammatory, and antiapoptotic effects that could offer protection against oxidative stress and liver damage. This study evaluated the hepatoprotective effect of omega-3 and vitamin C alone as well as in a combined form in methotrexate- (MTX-) induced acute liver injury in mice. Male ICR mice of seven groups (7 mice per group) were used. Groups 1 (control group) and 2 (MTX) received 0.9% saline/day (po) for 9 days. Groups 3 and 4 received 100 and 200 mg/kg bw/day omega-3 (po), respectively, for 9 days. Groups 5 and 6 received 100 and 200 mg/kg bw/day vitamin C (po), respectively, for 9 days, while group 7 received omega-3 (100 mg/kg bw/day) and vitamin C (100 mg/kg bw/day) (po) for 9 days. All animals in groups 2 to 7 received 20 mg/kg/day MTX (I.P.) once on the 10th day. Our results revealed that MTX significantly induced the elevation of transaminases, alkaline phosphates (ALP), lactate dehydrogenase (LDH), and malonaldehyde (MDA) while depleting the levels of superoxide dismutase (SOD) and glutathione (GSH) when compared to the control group. Treatment with omega-3 fatty acids or vitamin C significantly attenuated the antioxidants and biochemical alterations in a dose-independent manner. Our molecular docking study of ligand-receptor interaction revealed that both ascorbic acid and omega-3 docked well to the binding cavity of LDH with high binding affinities of –5.20 and –4.50 kcal/mol, respectively. The histopathological features were also improved by treatment with omega-3 and vitamin C. The combined form of omega-3 and vitamin C showed a remarkable improvement in the liver enzymes, oxidative stress biomarkers, and the histopathological architecture of the mice. Conclusively, the combination of omega-3 and vitamin C demonstrated a synergistic therapeutic effect against MTX-intoxicated mice, hence representing a potential novel strategy for the management of drug-induced liver disorders. [ABSTRACT FROM AUTHOR]

Balanites aegyptiaca L. Delile (B. aegyptiaca) is used in traditional medicine for the treatment of memory impairment. This work aims to evaluate the antioxidant and anticholinesterase potential of BA fruit pulp extract on excitotoxicity induced by monosodium glutamate (MSG). MSG was administered 30 minutes after treatment with B. aegyptiaca aqueous fruit pulp extract (50, 125, 250, and 500 mg/kg) and vitamin C (100 mg/kg) for 30 days. The negative control group received only MSG, while the control group was given distilled water daily. Behavioral tests parameters (using the novel object recognition, Y-maze, and Barnes maze tests), oxidative stress biomarkers (malondialdehyde, superoxide dismutase, and catalase), nitric oxide, and acetylcholinesterase activity and hippocampal architecture were evaluated. Results obtained revealed that different doses of B. aegyptiaca significantly reversed the deleterious effect of MSG on memory. This was displayed by a significant (p < 0.05) increment in the percentage of spontaneous alternation in the Y-maze test and a significant (p < 0.001) increase in discrimination index in novel object recognition observed with 500 mg/kg extract dose. Moreover, the extract (250 and 500 mg/kg doses) significantly (p < 0.001) increased direct search strategy and significantly decreased (p < 0.01) the time taken to find the target hole in the Barnes maze. A modulation of hyperactivity was observed after administration of all extract doses compared to the negative control group in the open arena. Furthermore, the highest dose of the extract caused a significant (p < 0.001) improvement in antioxidant enzymes activity, associated with a significant (p < 0.001) decrement in nitric oxide and malondialdehyde concentrations and a significant (p < 0.01) decrease in acetylcholinesterase activity. Treatment with the extract also restored normal hippocampal cell architecture. B. aegyptiaca fruit pulp extract could thus confer neuroprotection through its antioxidant and anticholinesterase potential. [ABSTRACT FROM AUTHOR]