Protective effects of ascorbic acid against anticancer drug-induced oxidative stress and genotoxic damage in Saccharomyces cerevisiae

抗坏血酸对酿酒酵母中抗癌药物诱导的氧化应激和基因毒性损伤的保护作用

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Abstract

The widely used dietary antioxidant ascorbic acid (AA) is evident to possess protective effects against many chronic diseases. This study aimed to evaluate the effects of AA on oxidative stress and genotoxic damage caused by 5-fluorouracil (5-FU), docetaxel (DOCE), and tamoxifen (TAMOX) in two proficient and four isogenic Saccharomyces cerevisiae strains. For this, we performed disc diffusion and comet alkaline assay using suitable standard drugs. The results suggest that 5-FU, DOCE, TAMOX, and their combinations induced significant oxidative damage (p < 0.001) in all S. cerevisiae strains. These anticancer drugs and their combinations also induced genotoxicity (p < 0.05) in the SODWT strain when compared to the negative control group. These drugs and their combinations augmented damage index (ID) and damage frequency (FD) in the comet assay. However, AA alone, as well as when co-treated with these anticancer drugs, significantly (p < 0.05) reduced the damaging effects (oxidative stress and genotoxicity) on all test strains. AA showed the highest damage modulation with TAMOX (ID = 51.4% and FD = 50%), followed by 5-FU + DOCE (ID = 43.5% and FD = 42.9%), DOCE (ID = 42.5% and FD = 39.1%), and 5-FU + TAMOX (ID = 37% and FD = 33.6%), respectively. Taken together, AA reduced oxidative stress caused by the inducer hydrogen peroxide and showed anti-genotoxic activities against 5-FU, DOCE, and TAMOX, and their combinations mediated genotoxic effects on S. cerevisiae strains. Further studies are necessary to understand the molecular interference of AA in cancer therapies.

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