Effects of intermittent fasting on the histology and mRNA expression of major drug-metabolizing cyp450s in the liver of diabetic mice

Abstract

ABSTRACT Introduction:There is a variation in drug response among patients who practice intermittent fasting. Alteration in the expression of drug-metabolizing enzymes (DMEs) can affect the pharmacokinetics and drug response. Aims: This research aimed to determine the effect of intermittent fasting on the mRNA expression of major drug-metabolizing cyp450s in the liver of diabetic mice. Methods: Thirty-two male Balb/c mice were divided into four groups; control, nonfasting diabetic, non-diabetic fasting, and diabetic fasting mice. Insulin-dependent diabetes was induced in mice by a single high-dose (250 mg/kg) streptozocin. Mice of non-diabetic and diabetic fasting groups were subjected to 10-day intermittent fasting for 17 hours daily. Then, the mRNA expression of mouse phase I DMEs cyp1a1, cyp2c29, cyp2d9, and cyp3a11 was analyzed using real-time polymerase chain reaction. In addition, the liver of mice in all groups was examined for pathohistological alterations. Results: Diabetes downregulated the mRNA expression of hepatic drug-metabolizing cyp450s in diabetic mice, while intermittent fasting significantly (P < 0.05) increased it. Also, cyp2d9 and cyp3a11 were upregulated in the liver of diabetic fasting mice. These alterations in the gene expression were correlated with the pathohistological alterations, where livers of diabetic mice showed dilatation in the blood sinusoids and inflammatory cells leukocyte infiltrations. Whereas livers of diabetic fasting mice showed almost comparable histological findings to control mice. Conclusions: Intermittent fasting can protect the liver against diabetes-induced hepatotoxicity and the down-regulation of DME genes in the diabetic liver. These results can explain, at least partly, the inter-individual variation in the drug response during practicing fasting.