CBrCl3-Toxicity In Isolated Rat Hepatocytes: Survey On Reasonable Cytotoxic Mechanisms

Summary

Isolated rat hepatocytes were exposed to 0.5, 1.0 and 1.5 mmol/l of the radical-inducing agent CBrCl₃.Viability as assessed by trypan blue exclusion, LDH release and intracellular K⁺ decreased in a dose-dependent manner and correlated well with lipid peroxidation as determined by MDA-formation. Early changes after haloalkane addition were a lower steady state-level of ATP and a marked inhibit ion of lysosomal neutral red uptake. Rise of cytosolic free Ca²⁺ and ß-glucuronidase release by lysosomes followed distinctly later. MTT-reduction, predominantly reflecting mitochondrial dehydrogenase activity, was diminished in a manner which revealed only a minor sensitivity to the radical insult. CBrCl₃-induced consumption of GSH was critical for the cytotoxic process only under conditions of inhibited GSSG-reduction or under artificial GSH-depletion.Thus, the concerted action of different pathobiochemical reactions rather than a single event seemed to ultimately cause the haloalkane-mediated lethal injury in hepatocytes.