Cystamine modulation of galactosamine-induced hepatotoxicity

The ability of cystamine treatment to protect against galactosamine-induced hepatic necrosis was investigated. Reduced hepatotoxicity was observed following galactosamine hydrochloride (400 mg/kg, ip) in male Sprague-Dawley rats that received cystamine dihydrochloride (300 mg/kg, po) 30 min prior to or 2, 4, 6, 8, or 12 hr after galactosamine, In contrast, uridine treatment only protected against galactosamine-induced liver damage if administered within 2 hr of galactosamine. Protection by cystamine was found to extend over 3 days during which time the lesion was resolving. The degree of protection was dose related when administered 12 hr after galactosamine. Cystamine did not prevent or alter the increase in hepatic Ca²⁺ seen following galactosamine administration. The results indicate that the protective effects of cystamine on galactosamine-induced hepatotoxicity are unrelated to prevention of the early biochemical events that initiate the injury. Furthermore, prevention of Ca²⁺ accumulation in damaged hepatocytes is not the mechanism of protection and hence is not necessarily an irreversible cytotoxic event.