title: Butenolide induced cytotoxicity by disturbing the prooxidant-antioxidant balance, and antioxidants partly quench in human chondrocytes.
abstract: Butenolide (BUT), a mycotoxin produced by Fusarium species, was detected often in corns or grains from endemic Kashin-Beck disease (KBD) areas in China. In this study, we evaluated the cytotoxicity of BUT on chondrocytes and the possible toxic mechanism with the aim of understanding the pathogenesis and of directing future therapeutic interventions for KBD. Exposure of human chondrocytes and engineered cartilage to high concentration of BUT (> 1 microg/ml) resulted in significant cytotoxicity, manifested by losses in cell viability and changes in cell morphology. BUT with high concentration (> 1 microg/ml) also induced significant oxidative damage to chondrocytes in vitro evidenced by increasing both lipid peroxidation and endogenous antioxidants. Furthermore, free radical scavenging agents, such as selenium (Se), vitamin C (VC) and vitamin E (VE), partly blocked BUT-induced oxidative damage. In conclusion, this finding indicates that BUT induces cytotoxicity to human chondrocytes, and the disturbance of prooxidant-antioxidant balance may play a pivotal role in BUT-induced injuries in chondrocytes. Moreover, Se, VC or VE can quench the toxic effects of BUT to a certain extent, which will possibly direct future therapeutic interventions against KBD.
authors.affiliation: Institute of Endemic Disease, Medicine College, Xi'an Jiaotong University, Ministry of Education, Xi'an Shaanxi 710061, PR China.
authors.forename: Zhongli
authors.initials: Z
authors.lastname: Shi
authors.forename: Junling
authors.initials: J
authors.lastname: Cao
authors.forename: Jinghong
authors.initials: J
authors.lastname: Chen
authors.forename: Siyuan
authors.initials: S
authors.lastname: Li
authors.forename: Zengtie
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Shuangqing
authors.initials: S
authors.lastname: Peng
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000633:toxicity; D001205:Ascorbic Acid / Q000494:pharmacology; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000196:embryology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010088:Oxidoreductases / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology; D023822:Tissue Engineering / Q000379:methods; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D007166:Immunosuppressive Agents; D014810:Vitamin E; C004511:butenolide; D010088:Oxidoreductases; D005978:Glutathione; D012643:Selenium; D015107:4-Butyrolactone; D001205:Ascorbic Acid