Curcumin Pretreatment Decreases Absorption of Phenacetin (Cytochrome P450 1A2 Substrate), Without Altering its Disposition Kinetics in Rats

Abstract

Many drugs used in the therapeutic regimen for various ailments undergo metabolism via cytochrome P450 1A2 (CYP1A2), so the agents or conditions altering the expression and/or activity of this enzyme play a significant role in therapeutic efficacy/failure of its substrates. Though curcumin is reported to be an inhibitor of CYP1A2, influence of curcumin on the pharmacokinetics of CYP1A2 probe phenacetin in rats has not yet been published to the best of our knowledge. Hence an attempt has been made to investigate the same. Two groups of wistar albino rats were taken, of which, one group received curcumin at 400 mg kg -1 , per os (PO) followed by phenacetin (150 mg kg -1 , PO) and the other received only phenacetin. Plasma concentrations of phenacetin, a known CYP1A2 substrate and its metabolite paracetamol were determined by high performance liquid chromatography. Based on plasma concentrations, the pharmacokinetic parameters were determined by compartmental methods. Curcumin pretreatment significantly (P \ 0.05) decreased peak plasma concentration (C max ) of phenacetin in rats. None of the other pharmacokinetic parameters of either phenacetin or paracetamol were affected. To conclude, curcumin pretreatment decreases C max of phenacetin but has no role on the disposition kinetics of either phenacetin or its metabolite paracetamol in rats. This implies that single dose of curcumin has no effect on CYP1A2 mediated metabolism in rats.

Curcumin ameliorates duodenal toxicity of AFB1 in chicken through inducing P-glycoprotein and downregulating cytochrome P450 enzymes

“…However, curcumin treatment could promote the recovery of normal functionality and morphology of the duodenum. It indicated that consumption of feed containing AFB1 would result in decreased nutrient digestion and absorption capacity of chickens, but curcumin could alleviate the AFB1-induced intestinal toxicity; these results were in according with previous studies ( Prasad et al, 2017 ).…”

“…AFB1 is extremely toxic, and has carcinogenic, teratogenic, and mutagenic effects on mammals and poultry ( Kalpana et al., 2012 ). It has been reported that duck fed on maize naturally contaminated with AFB1 had a negative effect on intestinal function and morphology, and altered digestive physiology and growth performance ( Prasad et al., 2016 ). In the present study, histopathological examination revealed that AFB1 could induce significant alteration in the functionality and morphology of the duodenum, including histological lesions, increase the length of the duodenum and the depth of the crypt, decrease the unit weight of the duodenum, the height of villus, and the value of V/C.…”