title: Desipramine ameliorates Cr(VI)-induced hepatocellular apoptosis via the inhibition of ceramide channel formation and mitochondrial PTP opening.
abstract: BACKGROUND
  Hexavalent chromium (Cr(VI)) is a common environmental pollutant. Cr(VI) exposure can lead to severe damage in the liver, but the preventive measures to diminish Cr(VI)-induced hepatotoxicity need further study. Acid sphingomyelinase (ASMase) is responsible for the production of ceramide via the hydrolysis of sphingomyelin. The present study was designed to investigate effects of desipramine (DES), as an ASMase inhibitor, on Cr(VI)-induced hepatotoxicity.
  
  
  METHODS
  L-02 hepatocytes were incubated with different concentrations of Cr(VI) for 24h, and ASMase activities and ceramide levels were measured. Moreover, the study investigated the role of DES played in ASMase activities and ceramide levels. Finally, effects of DES on mRNA and protein expressions of the components of mitochondrial permeability transition pore (PTP) and PTP opening were detected.
  
  
  RESULTS
  The ASMase activities and ceramide contents increased in L-02 hepatocytes treated with Cr(VI). The results demonstrated that apoptosis rates, ASMase activities and ceramide content decreased in groups treated with the combination of DES and Cr(VI) compared to Cr(VI) groups. Furthermore, DES inhibited Cr(VI)-induced mitochondrial PTP opening by intervening the mRNA and protein expressions of the components of mitochondrial PTP.
  
  
  CONCLUSIONS
  DES may exert protective effects on Cr(VI)-induced hepatocellular apoptosis probably by inhibiting ceramide channel formation and mitochondrial PTP opening.
authors.affiliation: Department of Health Toxicology, School of Public Health, Central South University, Changsha, People's Republic of China.
authors.forename: Lei
authors.initials: L
authors.lastname: Luo
authors.forename: Ying
authors.initials: Y
authors.lastname: Xie
authors.forename: An
authors.initials: A
authors.lastname: Wang
authors.forename: Xinmin
authors.initials: X
authors.lastname: Liu
authors.forename: Fang
authors.initials: F
authors.lastname: Xiao
authors.forename: Xiali
authors.initials: X
authors.lastname: Zhong
authors.forename: Caigao
authors.initials: C
authors.lastname: Zhong
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism*; D002857:Chromium / Q000633:toxicity; D003891:Desipramine / Q000008:administration & dosage*; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D033681:Mitochondrial Membrane Transport Proteins / Q000187:drug effects; D000083162:Mitochondrial Permeability Transition Pore; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism
chemical_list: D002518:Ceramides; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D002857:Chromium; C074702:chromium hexavalent ion; D013108:Sphingomyelin Phosphodiesterase; D003891:Desipramine