Plaa, GL; Hanasono, GK; Traiger, GJ; Witschi, HP
CC14-induced liver damage in mice and rats can be markedly potentiated by isopropanol (I), or acetone (A) pretreatment (Traiger and Plaa, J. Pharmacol. Exp. Ther. 183, 481, 1972). The objective of the present study was to determine if an 18-hr pretreatment with I (2.5 ml/kg, po) or A (1.0 ml/kg, po) could enhance the 24-hr hepatotoxic response produced by single doses of other necrogenic agents. In addition, the effect of I or A on the 24-hr hyperbilirubinemic response to alpha-naphthylisothiocyanate (ANIT) was examined at po doses of 100 or 300 mg/kg. SGPT activity after single ip doses of chloroform (0.5 ml/kg) or trichloroethylene (1.5 ml/kg) were approximately 41- and 8-fold higher, respectively, in I-pretreated mice. I produced little or no potentiation of SGPT activity in mice given ip 1,1,2-trichloroethane (0.15 ml/kg) or 1,1,1-trichloroethane (2.5 ml/kg); A also enhanced the response to chloroform, but had relatively little effect on the other compounds. I did not affect beryllium-induced changes in serum isocitric dehydrogenase (ICD) activity when rats were given single iv injections of Be and sacrificed 4 hr (39 μmol/kg) or 24 hr (7 or 17 μmol/kg) later. Similarly, I produced no increases in either serum ICD activity ofrats given allyl alcohol (10, 20 or 40 ml/kg, po), or in SGPT activity of rats given galactosamine HCl (200 or 400 mg/kg, ip). Thus, only necrogenic agents producing predominantly centrilobular damage were potentiated by I. A or I pretreatment enhanced the hyperbilirubinemic response (2-fold) of rats to ANIT at the higher dose only, suggesting that cholestatic responses may also be affected by I or A. (Supported by the Medical Research Council.)