The effect of chloroform inhalation on hepatic glucuronidation and de-glucuronidation mechanisms

The effect of 2, 4, 6 or 8 exposures to chloroform vapour on hepatic glucuronidating (UDPGA transferase) and de-glucuronidating (beta-glucuronidase) levels has been studied in rats. Successive treatments progressively decreased hepatic UDPGA transferase to a minimum of 53% of the control level. beta-Glucuronidase activity was increased two-fold after only two exposures and remained elevated for subsequent exposures. Cytochrome P450 levels decreased with each exposure. The level of this coenzyme in the treated animals remained lower than that of the control animals for at least 48 hours after treatment. UDPGA transferase was diminished to its lowest levels 9 hours after the final exposure to chloroform and did not achieve the control value for a further 48 hours. The beta-glucuronidase activity remained elevated for 12 hours after final exposure. The present experiment demonstrates that inhalation of toxic solvents such as chloroform decreases the glucuronidating capacity of the liver.