Apoptosis in liver damage produced by tunicamycin

OBJECTIVE: To determine whether apoptosis contributes to hepatocyte loss in tunicamycin poisoning. DESIGN: Groups of four guinea pigs were given 400 microg/kg of tunicamycin subcutaneously and killed at 24 h intervals up to 72 h post-injection. Livers were examined by routine histological methods and ancillary techniques (TUNEL staining, endonuclease activation, caspase activity, and electron microscopy) to ascertain whether any hepatocyte injury was apoptotic. RESULTS: Many hepatocytes exposed to tunicamycin showed evidence of apoptosis in the form of nuclear karyorrhexis with chromatin margination and crescent formation, TUNEL-positivity, DNA laddering, elevated caspase activity and apoptotic body formation. CONCLUSION: Tunicamycin caused the death of many hepatocytes in the livers of guinea pigs by apoptosis.