The Influence of Fasting on the Activity of Some Hepatotoxic Agents

Abstract

The hepatotoxic effects of 8 compounds were investigated in normally fed mice on the one and in 24-hours fasted mice on the other hand. The extent of liver damage was evaluated by determination of serum enzyme activities (GOT, GPT, SDH) 24 hours (praseodymium 72 hours) after intraperitoneal injection of the hepatotoxic agents. Body weight of the mice declined by 23% and liver weight by 29% after 24 hours food deprivation. Fasting strongly enhanced the hepatotoxic effects of carbon tetrachloride (0.02 ml/kg), paracetamol (350 mg/kg), thioacetamide (35 mg/kg), and bromobenzene (0.25 ml/kg). The hepatotoxic actions of phalloidine (1.5 mg/kg) and allyl alcohol (0.1 ml/kg) were only increased moderately, and those of α-amanitine (0.75 mg/kg) and praseodymium (200 mg/kg) not at all. In rats, 24-hours fasting enhanced the hepatotoxic action of carbon tetrachloride (0.1 ml/kg), too. Feeding a protein-free diet during 24 hours, however, did not enhance carbon tetrachloride-induced hepatotoxicity in mice. 24-hours fasting increased p-hydroxylation of aniline in the 9000 · g supernatant of mouse liver homogenate from 2.24±0.13 to 3.31±0.18 μmol/g liver and diminished glutathione concentration in the mouse liver from 4.26±0.35 to 1.96±0.52 μmol/g liver. The enhanced hepatotoxic response after fasting is presumably due to 1) a higher conversion rate of the hepatotoxines to toxic metabolites and 2) a lower detoxification rate (conjugation with glutathione).