Acrolein scavengers, cysteamine and N-benzylhydroxylamine, reduces the mouse liver damage after acetaminophen overdose.
Our previous study suggested that the highly toxic α,β-unsaturated aldehyde acrolein, a byproduct of oxidative stress, plays a major role in acetaminophen-induced liver injury. In this study, to determine the involvement of acrolein in the liver injury and to identify novel therapeutic options for the liver damage, we examined two putative acrolein scavengers, a thiol compound cysteamine and a hydroxylamine N-benzylhydroxylamine, in cell culture and in mice. Our results showed that cysteamine and N-benzylhydroxylamine effectively prevented the cell toxicity of acrolein in vitro and acetaminophen-induced liver injury in vivo, which suggested that acrolein is involved in the liver damage, and these two drugs can be potential therapeutic options for this condition.
Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278-0022, Japan.
Ryo
R
Koyama
Ryushin
R
Mizuta
D000082:Acetaminophen / Q000633:toxicity*; D000171:Acrolein / Q000633:toxicity*; D000818:Animals; D045744:Cell Line, Tumor; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003543:Cysteamine / Q000494:pharmacology* / Q000627:therapeutic use; D062787:Drug Overdose / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D006898:Hydroxylamines / Q000494:pharmacology* / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism
D006898:Hydroxylamines; D017382:Reactive Oxygen Species; D000082:Acetaminophen; D003543:Cysteamine; D000171:Acrolein