title: The profound effects of microcystin on cardiac antioxidant enzymes, mitochondrial function and cardiac toxicity in rat.
abstract: Deaths from microcystin toxication have widely been attributed to hypovolemic shock due to hepatic interstitial hemorrhage, while some recent studies suggest that cardiogenic complication is also involved. So far, information on cardiotoxic effects of MC has been rare and the underlying mechanism is still puzzling. The present study examined toxic effects of microcystins on heart muscle of rats intravenously injected with extracted MC at two doses, 0.16LD(50) (14 microg MC-LReq kg(-1) body weight) and 1LD(50) (87 microg MC-LReq kg(-1) body weight). In the dead rats, both TTC staining and maximum elevations of troponin I levels confirmed myocardial infarction after MC exposure, besides a serious interstitial hemorrhage in liver. In the 1LD(50) dose group, the coincident falls in heart rate and blood pressure were related to mitochondria dysfunction in heart, while increases in creatine kinase and troponin I levels indicated cardiac cell injury. The corresponding pathological alterations were mainly characterized as loss of adherence between cardiac myocytes and swollen or ruptured mitochondria at the ultrastructural level. MC administration at a dose of 1LD(50) not only enhanced activities and up-regulated mRNA transcription levels of antioxidant enzymes, but also increased GSH content. At both doses, level of lipid peroxides increased obviously, suggesting serious oxidative stress in mitochondria. Simultaneously, complex I and III were significantly inhibited, indicating blocks in electron flow along the mitochondrial respiratory chain in heart. In conclusion, the findings of this study implicate a role for MC-induced cardiotoxicity as a potential factor that should be considered when evaluating the mechanisms of death associated with microcystin intoxication in Brazil.
authors.affiliation: Donghu Experimental Station of Lake Ecosystems, State Key Laboratory for Freshwater Ecology and Biotechnology of China, Institute of Hydrobiology, The Chinese Academy of Sciences, Wuhan 430072, PR China.
authors.forename: Tong
authors.initials: T
authors.lastname: Qiu
authors.forename: Ping
authors.initials: P
authors.lastname: Xie
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Guangyu
authors.initials: G
authors.lastname: Li
authors.forename: Qian
authors.initials: Q
authors.lastname: Xiong
authors.forename: Le
authors.initials: L
authors.lastname: Hao
authors.forename: Huiying
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D004798:Enzymes / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D052998:Microcystins / Q000008:administration & dosage / Q000633:toxicity*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D019210:Troponin I / Q000097:blood
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004798:Enzymes; D052998:Microcystins; D012333:RNA, Messenger; D019210:Troponin I; D008315:Malondialdehyde; C078588:microcystin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione