The interactions between retinol and five different hepatotoxicants in the Swiss Webster mouse.
The interactive effects between retinol and various hepatotoxicants (allyl alcohol, acetaminophen, carbon tetrachloride, D-galactosamine, and phalloidin) were studied in the male Swiss Webster mouse. The mice were administered retinol at 75 mg/kg/day (or the vehicle of retinol) by oral gavage for 7 days. Hepatoxicity produced by the chemicals was determined by plasma alanine aminotransferase (ALT) activity and histopathology. After 7 days of retinol pretreatment, the hepatotoxicities of allyl alcohol, acetaminophen, and galactosamine were potentiated. Interestingly, the hepatotoxicity of carbon tetrachloride and phalloidin was protected by identical retinol pretreatment. Microscopic examination of histologic liver sections demonstrated the specific hepatic necrosis associated with each individual chemical and confirmed the ALT values obtained. Once an interaction between retinol and the five hepatotoxicants was established, the duration of retinol pretreatment necessary to elicit an interaction was determined for each hepatotoxicant. Results demonstrated that the duration of retinol pretreatment was specific for each hepatotoxicant. The accumulation of retinoids in the liver during retinol pretreatment was determined using high-performance liquid chromatography analysis. Significant increases in the basal liver levels of retinol and retinyl palmitate were seen within 1 to 3 days of retinol treatment compared to control. Retinol pretreatment resulted in potentiation or protection of specific hepatotoxicant-induced liver damage. Currently, studies are being conducted which probe into the mechanisms of these interactions.
Rosengren
R J
RJ
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Sauer
J M
JM
Hooser
S B
SB
Sipes
I G
IG
D000433:1-Propanol / Q000633:toxicity; D000082:Acetaminophen / Q000633:toxicity*; D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D004224:Diterpenes; D004347:Drug Interactions; D004357:Drug Synergism; D005688:Galactosamine / Q000633:toxicity*; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D010590:Phalloidine / Q000633:toxicity*; D020005:Propanols; D012176:Retinoids / Q000032:analysis; D000084562:Retinyl Esters; D000637:Transaminases / Q000032:analysis; D014801:Vitamin A / Q000031:analogs & derivatives / Q000032:analysis / Q000633:toxicity*
D004224:Diterpenes; D020005:Propanols; D012176:Retinoids; D000084562:Retinyl Esters; D014801:Vitamin A; D010590:Phalloidine; C014794:retinol palmitate; D000082:Acetaminophen; C006463:allyl alcohol; D005688:Galactosamine; D000433:1-Propanol; D002251:Carbon Tetrachloride; D000637:Transaminases