Temporal variations in chloroform-induced hepatotoxicity in rats

There is increasing evidence to show that drug metabolism and effects are modulated by biological rhythms; therefore the possibility that chloroform (CHCl3) induced acute hepatotoxicity may also vary as function of time of administration was investigated in male Sprague--Dawley rats. The animals were given a single intraperitoneal dose of CHCl3 or saline, 0.5 ml/kg, at 09:00 h, 13:00 h, 17:00 h, 21:00 h or 03:00 h and killed 4 h after treatment. The hepatotoxicity induced by CHCl3 was determined by the serum glutamic-pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT) and lactic dehydrogenase (LDH) activities and by the glucose-6-phosphatase (G6Pase) activity of the liver. The increases in SGPT, SGOT and LDH were minimal and maximal when the organic solvent was injected at 09:00 h and 21:00 h, respectively, whilst the activity of G6Pase was depressed significantly at 03:00 h and 13:00 h under similar conditions. Starving the rats for 16 h prior to the injection of CHCl3 at 09:00 h increased substantially the hepatotoxicity as measured by the above enzyme activities. These findings may be relevant in the toxicity of CHCl3 in industrial workers exposed to this solvent at various times of the day.