Astaxanthin Mitigates 5-Fluorouracil-Induced Hepatotoxicity and Oxidative Stress in Male Rats

Background: Hepatotoxicity, a significant complication of 5-fluorouracil (5-FU) treatment, is generally triggered by oxidative stress, liver damage, and apoptosis processes that take place in cancer patients. Methods: In this study, the protective effect of different astaxanthin (ASX) dosages (16 and 32/mg/kg/bw) was determined in rats with 5-FU-induced liver damage. Results: 5-FU induced a significant increase in the histopathological lesions severity and immunohistochemical (TNF-α and 8-OHdG) expression scores in the liver (p < 0.001), significantly increased serum liver parameters (AST, ALP, ALT, GGT, and TP) and malondialdehyde (p < 0.001), and, at the same time, significantly decreased antioxidant parameters (SOD, CAT, GST, GSR, Caspase-3, and GPx) (p < 0.001). Histopathological lesions and oxidative stress parameters significantly decreased in parallel while increasing the ASX dosage (p < 0.001). Conclusions: Based on these data, our results suggest that ASX may be considered a promising and valuable agent to mitigate hepatotoxicity and resistance mechanisms during cancer treatment.