Effect of food restriction on UDP-glucuronosyltransferase (UGT) enzymes in liver

Abstract

Purpose The influence of diet and nutritional status on drug metabolism has been widely documented. Hepatic drug metabolism enzymes can be profoundly altered in patients suffering from malnutrition and starvation. In this research we have studied the effect of food restriction on UDP-glucuronosyltransferase (UGT) enzymes in rat liver. Methods Male Sprague-Dawley rats were maintained on a powdered commercial diet. Rats in control group (C, n=4) had ad libitum access to food and water. Animals in food restriction group (FRG, n=5) were fed with 60% of food intake of the control group. After 5 weeks, the rats were sacrificed and liver microsomes were prepared. Protein content was assessed by Western blot using polyclonal antibody for rat UGT1A1, human UGT1A6, and rat UGT1A7. Results The body weight of the FRG rats was reduced by 35% compared to the C rats. Hepatic and renal organ function was normal between the two groups. Western blot results revealed that antibody against human UGT1A6 cross-reacted with rat UGT1A6. The polyclonal antibodies were found to be specific for the UGTs. Food restriction did not have any influence on protein content of hepatic UGT1A1 and UGT1A7. However, the UGT1A6 protein levels were significantly lower (p<0.05) in the FRG rats (~3-fold reduction) compared to control animals. Conclusion Food restriction appears to selectively downregulate hepatic UGT enzymes in male rats. Clinical Pharmacology & Therapeutics (2004) 75, P85–P85; doi: 10.1016/j.clpt.2003.11.326