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.
- Research Organization:
- Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson
- OSTI ID:
- 7012249
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 73:3; ISSN TXAPA
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINES
ANIMALS
BIOLOGICAL EFFECTS
BODY
CYSTAMINE
DIGESTIVE SYSTEM
DRUGS
GLANDS
LIVER
MAMMALS
NECROSIS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PATHOLOGICAL CHANGES
RADIOPROTECTIVE SUBSTANCES
RATS
RESPONSE MODIFYING FACTORS
RODENTS
TOXICITY
VERTEBRATES