Characterization of Vitamin A Potentiation of Carbon Tetrachloride-Induced Liver Injury

• Published in: Toxicology and applied pharmacology Vol. 119; no. 2; pp. 280 - 288
• Main Authors: Elsisi, A.E.D., Hall, P., Sim, W.L., Earnest, D.L., Sipes, I.G.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.04.1993; Elsevier
• Subjects: 1-Propanol - pharmacology; Acetaminophen - pharmacology; Alanine Transaminase - blood; Alanine Transaminase - drug effects; Animals; Biological and medical sciences; Carbon Tetrachloride - toxicity; Chemical and Drug Induced Liver Injury; Chemical and industrial products toxicology. Toxic occupational diseases; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Synergism; Endotoxins - pharmacology; ENVENENAMIENTO; FOIE; HIGADO; INTOXICATION; Liver Diseases - metabolism; Liver Diseases - pathology; Male; Medical sciences; Propanols; RAT; RATA; Rats; Rats, Sprague-Dawley; RETINOL; TETRACHLORURE DE CARBONE; TETRACLORURO DE CARBONO; TOXICIDAD; TOXICITE; Toxicology; Various organic compounds; Vitamin A - analogs & derivatives; Vitamin A - metabolism; Vitamin A - pharmacology; Potentiation; Intraperitoneal administration; Rat; Enzyme; Toxicity; Carbon tetrachloride; Rodentia; Vitamin; Oral administration; Hepatic disease; Dose activity relation; Retinol; Hepatitis; Vertebrata; Mammalia; Enzymatic activity; Animal; Digestive diseases; D-Alanine aminotransferase
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1993.1070

Pretreatment of rats with large doses of vitamin A (VA, retinol) has been shown to potentiate carbon tetrachloride hepatotoxicity. The relationship between VA dose or pretreatment duration with VA and the extent of potentiation of CCl 4 hepatotoxicity is unknown. Therefore, VA was administered to male SD rats (180-200 g) by oral gavage in daily doses of 100,000, 150,000, 200,000, or 250,000 IU/kg for 3 weeks. In another experiment, rats were given VA in a daily dose of 250,000 IU/kg for 1 day, 1, 2, 3, or 5 weeks. At 24 hr after the last VA dose, CCl 4 (0.15 ml/kg, ip) was administered. Hepatotoxicity was assessed by increases in plasma alanine aminotransferase activity and by histological evaluation of the liver. Additionally, the correlation between the hepatic concentration of retinol and retinyl palmitate after VA treatment and the extent of potentiation of CCl 4-induced liver injury was studied. In the initial 3-week dose-response study, as the daily dose of VA increased so did the degree of potentiation of CCl 4 hepatotoxicity. All treatment durations with VA (250,000 IU/kg per day), except 1 day, resulted in equivalent potentiation of CCl 4 hepatotoxicity. VA treatment did not result in elevated hepatic concentration of retinol. However, VA treatment did increase the concentration of retinyl palmitate in the liver (except for the 1-day treatment). No linear correlation could be seen between the hepatic concentration of retinyl palmitate and the extent of VA potentiation of CCl 4 hepatotoxicity. VA treatment also potentiated to hepatotoxicity of minimally hepatotoxic doses of acetaminophen, allyl alcohol, and endotoxin. Because these chemicals produce hepatic injury by diverse mechanisms it is concluded that VA potentiates hepatic injury by altering a process involved in the progression of cell injury.