Suramin: potential in acute liver failure.
Apoptosis is the first cellular response of the liver to many toxic events, including viral hepatitis, alcohol-induced liver disease and ischaemia/reperfusion injury. When apoptosis is induced with an antibody to APO-1, suramin is antiapoptotic in a variety of cell lines (e.g., Jurkat cells, HepG2). Jo2 is an antibody to mouse CD95, which kills C57Bl/6 mice, and was used as a model of fulminant liver failure in mice. Suramin protected 40% of Jo2-treated mice from death and delayed death in the other mice. In mice, D-galactosamine and endotoxin cause apoptotic liver damage, which is mediated by TNF. Suramin reduced this liver damage as assessed by serum aminotransferase levels, gross liver appearance and apoptosis levels. In contrast, suramin does not inhibit necrotic cell death in a rat model of liver transplantation. Inhibition of apoptosis with suramin or other more selective agents is an approach that should be further investigated in liver failure.
Doggrell
Sheila A
SA
Doggrell Biomedical Communications, 47 Caronia Crescent, Lynfield, Auckland, New Zealand. s.doggrell@xtra.com
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D004195:Disease Models, Animal; D006801:Humans; D017114:Liver Failure, Acute / Q000188:drug therapy*; D013498:Suramin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity
D013498:Suramin