Mitochondrial lipid peroxidation and microsomal drug-metabolizing enzyme activity of rat hepatotoxicity under heavy metals from slag waste exposure

Abstract

Heavy metals from slag waste (HMSWs) have been a long-term concern around the world, posing serious environmental and visceral toxicity, especially hepatotoxicity. Investigating the leaching behavior and hepatotoxicity of HMSWs is of great significance. Based on the toxicogenomic analysis, the targets and related signaling pathways of heavy metal-induced liver injury were predicted, and the effects of different HMSWs on mitochondrial lipid peroxidation injury and microsomal drug-metabolizing enzyme activities in rats were experimentally explored. The results showed that different heavy metals might have the function of interfering with physiological processes such as oxidative stress, cell death, and energy metabolism regulation in vivo, and participate in the regulation of HIF-1 signaling pathway, peroxisomes, drug metabolism-cytochrome P450, ferroptosis, and other signaling pathways. HMSWs exposure caused weight loss, and significantly increased lactate dehydrogenase (LDH), malondialdehyde (MDA), alanine transaminase (ALT), and aspartate transaminase (AST) in different groups of rat liver, suggesting the presence of mitochondrial lipid peroxidation damage. Meanwhile, the activities of superoxide dismutase (SOD) and mitochondrial membrane potential (MMP) in the liver were significantly decreased, and microsomal Cytochrome P450 1A2 (CYP1A2) and 3A1 (CYP3A1) enzyme activities were induced, predicting the involvement of the microsomal drug-metabolizing enzymes. These results indicated that metabolic interplay between microsomes and other subcellular organelles including mitochondria and peroxisome could be involved in heavy metals-induced liver injury.

CHEMOPREVENTIVE POTENTIAL OF ALCOHOLIC EXTRACT OF A POLYHERBAL ( Phyllanthus amarus, Euphorbia hirta and Azadirachta indica) RECIPE AGAINST BENZO(a)PYRENE INDUCED LUNG CARCINOGENESIS IN ALBINO MICE

“…The disruption of the integrity of biochemical processes in mice induced with BaP in the study was assessed to understand the impact of administering the polyherbal recipe on mice exposed to B(a)P by monitoring changes in serum enzyme activities, which reflect the disruption of biochemical processes. The liver primarily metabolizes foreign substances through various enzymes such as microsomal enzymes, aminotransferases, and oxygenases 92 . The liver exhibits high metabolic flexibility by inducing these enzymes to metabolize different compounds and regulating gene expression for their synthesis.…”

“…In assessing organ damage, liver and kidney markers are commonly examined changes in transaminases (ALT, AST, and ALP) as well as renal markers (CREAT, BUN, and Chol). Cell damage in various organs often leads to the release of specific cytoplasmic enzymes into the bloodstream, and increased levels of these compounds in serum or plasma can aid in clinical diagnosis 92,93 . The study observed a significant increase in the activities of serum biochemical parameters (AST, ALT, ALP, BUN, CHOL, and CREAT) in the PC group (BaPtreated groups), accompanied by decreases in the other groups (BaP + Polyherbal recipe).…”