Oxidative Stress Injuries Induced By Butenolide And Its Mechanisms

Butenolide (BUT) is one of the mycotoxins produced by Fusarium. It can cause various toxic effects in animals, and represents a potential imperilment to human and animal health, but the possible mechanisms involved in its toxicities remain to be elucidated so far. Previous study indicated that BUT could induce lipid peroxidation in animals, but its role in the toxicity of BUT was unknown. In this study, biomembrane toxicology was applied to evaluate the toxic effects of BUT on isolated erythrocyte membranes. We also investigated the effects of BUT on the redox status in HepG2 cells, the cytotoxicity of BUT, and the possible cytotoxic mechanism from the viewpoint of oxidative injuries.BUT induced erythrocyte membrane lipid peroxidation significantly, shown by a startling increase in the level of malondialdehyde (MDA). BUT resulted in obvious oxidative injuries to the structure and functions of membrane proteins: decrement of membrane thiol content, inhibition of the activities of membrane-bound Na⁺/K⁺-ATPase and Ca²⁺/Mg²⁺-ATPase, increase in the W/S ratio and decrease in the rotation correlation time (Ï„_c) of the membrane proteins. BUT had no obvious effects on the activity of acetylcholinesterase (AChE), the content of sialic acid (SA), and the protein compositions of erythrocyte membranes.BUT induced a significant decrease in the content of intracellular glutathione (GSH) and protein -SH (P-SH), concomitantly an obvious increase in the production of intracellular reactive oxygen species (ROS) in HepG2 cells. BUT also induced decreases in the activities of intracellular antioxidant enzymes, such as catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px). In addition, BUT induced lipid peroxidation significantly in HepG2 cells. These results indicated that BUT could induce significant intracellular oxidative stress.Results showed that BUT had obvious cytotoxicity, it reduced cell viability in a concentration- and time-dependent manner, and resulted in the leakage of intracellular lactate dehydrogenase (LDH). It was found that the oxidative stress (GSH depletion...