α-LA attenuates microcystin-LR-induced hepatocellular oxidative stress in mice through Nrf2-mediated antioxidant and detoxifying enzymes.

ABSTRACT

Microcystins constitute a class of toxins synthesized by cyanobacteria and are known to inflict significant damage on the antioxidant defense system of living organisms, primarily targeting the liver. α-Lipoic acid (α-LA) is universally recognized as a potent antioxidant in biological systems. It exerts its beneficial effects through multiple mechanisms-directly neutralizing reactive oxygen species (ROS) and free radicals, and indirectly enhancing antioxidant defenses by facilitating the regeneration of glutathione (GSH). However, the precise modus operandi of α-LA's protective effect against Microcystin-LR-induced hepatotoxicity remains incompletely elucidated. The present study, therefore, employed α-LA to explore its protective role against Microcystin-LR exposure in mice. A model of Microcystin-LR-induced hepatic injury was established by administering Microcystin-LR into the peritoneal cavity of BALB/c mice daily over a two-week period. Thereafter, BALB/c mice were pre-treated with varying concentrations of α-LA via oral gavage for a duration of 7 days, followed by a 7-day exposure to Microcystin-LR. Our findings reveal that α-LA pre-treatment significantly mitigated hepatic pathologies in Microcystin-LR-exposed mice. Furthermore, α-LA administration led to a notable elevation in the activities and expression levels of nuclear factor erythroid 2-related factor 2, superoxide dismutase, glutathione peroxidase, glutathione S-transferase, and glutathione-indicative of its antioxidative capacity. Concurrently, a significant decrease was observed in the activities and expression levels of malondialdehyde and cytochrome P450 2E1. Consequently, α-LA emerges as a promising therapeutic candidate for the amelioration of liver oxidative damage subsequent to Microcystin-LR exposure.