Betaine Mitigates Paclitaxel-Induced Hepatotoxicity in Rats by Regulating Oxidative Stress, Inflammation, Apoptosis, and Autophagy.

Paclitaxel (PTL) is widely used in chemotherapy; however, its efficacy is compromised by the risk of liver toxicity. This is the first study to investigate the protective effect of betaine (BTN) against PTL-induced liver injury. Rats were randomly divided into five experimental groups (n = 7 per group): control (saline), BTN (100 mg/kg/day), PTL (2 mg/kg/day), PTL + BTN (2 and 50 mg/kg/day), and PTL + BTN (2 and 100 mg/kg/day). After the rats received 2 mg/kg body weight PTL intraperitoneally for the first five consecutive days, BTN was administered orally for 10 days. Our results indicate that BTN restores liver antioxidant levels (SOD, FRAP, and GSH), improves liver function by lowering AST and ALT levels, and attenuates PTL-induced lipid peroxidation. In the livers of PTL-treated rats, BTN significantly decreased the levels of NF-κB and TNF-α proteins and the ratio of caspase-3/pro-caspase-3, whereas it increased the levels of Nrf2, LC3-II/LC3-I, and Bcl-2. In summary, the results of this study suggest that BTN may ameliorate PTL-induced liver injury by regulating oxidative stress, inflammation, apoptosis, and autophagy.