Age-dependent features of CYP3A, CYP2C, and CYP2E1 functioning at metabolic syndrome

Abstract

AbstractBackground:Complex investigations of cytochrome P450 (CYP) isoforms with metabolic syndrome (MS) development are limited, and specific features of adolescent’s metabolisms are generally disregarded. The aim of present study was a comparative estimation of MS-mediated changes in CYP3A, CYP2C, and CYP2E1 mRNA expression and enzymatic activities, as well as antioxidant system parameters of adult and pubertal rats.Methods:Wistar albino male rats of two age categories [young animals of 21 days age (50–70 g) and adults (160–180 g)] were divided into four groups (eight animals in each group): (1) control 1 (intact young rats), (2) control 2 (intact adult rats), (3) MS3 (young rats with MS), and (4) MS4 (adult rats with MS). The MS was induced by full replacement of drinking water by 20% fructose solution (200 g/L). After 60 days of MS modeling, the investigation of rat liver CYP3A, CYP2C, and CYP2E1 mRNA expressions, their enzyme-marker activities, as well as the antioxidant system parameters was conducted.Results:Levels of liver CYP2E1 mRNA expression increased with MS: 40% (adults) and 80% (pubertal rats). Pubertal rats had also increased CYP3A2 mRNA expression (30%) and decreased CYP2C mRNA expression (30%). Changes in CYP2E1 and CYP2C enzymatic activities were consistent with the changes of corresponding gene expressions at both age-groups with MS. Simultaneously, liver reduced glutathione contents, and glutathione transferase and reductase activities were decreased in pubertal animals.Conclusions:CYP isoform expression rates and glutathione system were greatly violated with MS. The greater changes were observed in pubertal rats with MS.