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 signi cance. 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 signi cantly 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 signi cantly 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.

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.