title: The role of ROS in microcystin-LR-induced hepatocyte apoptosis and liver injury in mice.
abstract: Microcystin-LR (MC-LR) produced by cyanobacteria in diverse water systems is a potent specific hepatotoxin and has been documented to induce hepatocyte apoptosis and liver injury; however, the mechanisms have not been fully elucidated. In the present study, we investigated whether MC-LR stimulated ROS generation in the liver of mice and the role of ROS in the pathogenesis of MC-LR-induced liver injury in vivo. MC-LR treatment (60 microg/kg of body weight) for 12h prompted large amount of ROS generation in mice liver, upregulated the expression of Bax and Bid, caused the mitochondrial membrane potential (MMP) loss and hepatocyte apoptosis as well as liver injury. While pretreatment with antioxidants, oral administration of vitamin C (250mg/kg of body weight, dissolved in double distill water) and vitamin E (200mg/kg of body weight, dissolved in corn oil) per day for 3 days continually, significantly reduced the generation of ROS and effectively inhibited the MC-LR-induced hepatocyte apoptosis and liver injury, suggesting that ROS played a critical role in MC-LR-induced hepatocyte apoptosis and liver injury. The protective effect of vitamin C and E also suggested the potential interest in the clinical treatment of MC-LR-induced liver injury and hepatotoxicity.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Weng
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Yinna
authors.initials: Y
authors.lastname: Wei
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Pingping
authors.initials: P
authors.lastname: Shen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001205:Ascorbic Acid / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D051023:BH3 Interacting Domain Death Agonist Protein / Q000096:biosynthesis / Q000235:genetics; D056486:Chemical and Drug Induced Liver Injury; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006651:Histocytochemistry; D008107:Liver Diseases / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008387:Marine Toxins; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D052998:Microcystins / Q000633:toxicity*; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012235:Rhodamines / Q000737:chemistry; D014810:Vitamin E / Q000494:pharmacology; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000975:Antioxidants; D051023:BH3 Interacting Domain Death Agonist Protein; C494827:Bax protein, mouse; C494815:Bid protein, mouse; D008387:Marine Toxins; D052998:Microcystins; D017382:Reactive Oxygen Species; D012235:Rhodamines; D051028:bcl-2-Associated X Protein; C058319:dihydrorhodamine 123; D014810:Vitamin E; D008315:Malondialdehyde; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C057862:cyanoginosin LR; D001205:Ascorbic Acid