Effect of nafenopin on the liver peroxisomal enzymes activities in rats

The effects of different doses of the fibric acid derivative nafenopin [NAF] on peroxisomal enzymes in control [saline-treated] and diethylnitrosamine [DEN]-treated rats were studied. The catalase activity was induced 1.3, 2.1, 2.2 or 2.3-fold in control rats receiving 0.01, 0.05, 0.1 or 0.25% NAF admixed with food, respectively. Figures for animals receiving these doses post pretreatment with DEN were 1.1, 1.7, 1.9 or 2.3-fold, respectively. In control rats, the values for induction of Acyl CoA oxidase activity, produced by diet containing 0.01, 0.05, 0.1 or 0.25% NAF, were 6, 25, 34 and 30-fold, respectively. In DEN-treated rats, however, the corresponding values were 6, 28, 46 and 67-fold, respectively. The D-amino acid oxidase activity as well as that of glycolate oxidase were significantly depressed. This depression of activities was dose related in both control and DEN-treated rats. The results indicated that induction of the peroxisomal enzymes in the rat is a rather specific process which could be influenced by treatment with the hepatocarcinogen [DEN]. In DEN-treated rats, the overproduction of hydrogen peroxide [H2O2], [as reflected by the significant increase in the activity of H2O2-producing enzyme: Acyl CoA oxidase], induced by NAF treatment, could thus be higher than in the control rats. Additionally, since the doses of NAF employed in the present study are known to modulate neoplastic development, an imbalance between H2O2 production and catabolism is thought to play a major role in this process

Disposition of glipizide in patients with liver cirrhosis

The effect of moderate alcoholic liver cirrhosis, in nondiabetic patients, on the kinetics of a single oral dose [5 mg] of the hypoglycemic sulfonylurea agent, glipizide [GPZ], was investigated. The results were compared with those reported for healthy subjects and diabetic patients. The study revealed that there was no significant alteration in the pharmacokinetics profile of GPZ under moderate liver cirrhosis. However, in one patient, who had moderate cirrhosis accompanied by fibrosis, there was a marked increase in half-life [2.4 v 8.6 h] and AUC [3710 v 13171 nmol L -1 h] and large reduction in clearance [2.96 v 0.83 L h -1] when compared with a matching healthy subject. The results suggested that liver fibrosis may contribute to alteration in the kinetics of GPZ