APOPTOSIS INDUCED IN RAT HEPATOCYTES BY IN-VIVO EXPOSURE TO TAUROCHENODEOXYCHOLATE

Enzymatic and molecular cytochemistry was used to detect and follow th e hepatotoxic effects caused in overnight-fasted Sprague-Dawley rats b y a 1-h continuous intrafemoral infusion of taurochenodeoxycholate at 0.4 and 0.8 mu mol(-1) min(-1) 100 g(-1) body weight dose levels. Rats were killed at 0, 1 and 24 h from the end of perfusion. Their livers were examined for morphology, DNA fragmentation (by a TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP-nick end-labelling assay), cell regeneration (by in vivo bromodeoxydurine incorporation), reduced glutathione, calcium and several enzyme cytochemical activities. Isol ated injured hepatocytes randomly scattered throughout the liver were already evident at the end of perfusion. DNA fragmentation and cytopla sm shrinkage were prominent and early features of injured hepatocytes, which later showed calcium loading and chromatin clumping. Preserved cytochemical enzymatic activities indicated that plasma and mitochondr ia membranes were not severely damaged. Inflammatory response was abse nt. These observations indicate that an acute exposure to taurochenode oxycholate induces a cell death process with apoptotic features.