Effects of dietary fish oil on cytochrome P450 3A expression in the liver of SHR/NDmcr-cp (<i>cp</i>/<i>cp</i>) rats, an animal model for metabolic syndrome

Abstract

Pathophysiological and nutritional conditions often affect the expression of drug-metabolizing enzymes. SHR/NDmcr-cp (cp/cp) rats (SHR/NDcp) are highly suitable as a metabolic syndrome (MS) model. Nevertheless, little is known about the expression profile of cytochrome P450 (CYP) in the liver of SHR/NDcp. We thus attempted to clarify the expression profile of CYP genes and the effect of fish oil (FO) on this profile in the liver of SHR/NDcp. Lower levels of CYP3A2 mRNA and CYP3A activity (testosterone 6β-hydroxylation) were distinctive features in SHR/NDcp compared with their controls (Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR), stroke-prone SHR and lean littermates of SHR/NDcp). Differently from CYP3A2, the expression of other CYP isoforms was largely unchanged in SHR/NDcp. The changes in CYP profile observed in SHR/NDcp are similar to those of patients with diabetes and simple hepatic steatosis. Feeding on FO at a high dose (18.8% in the diet) upregulated CYP3A2 gene expression and CYP3A activity in the liver; the extent of these increases was greater in SHR/NDcp than in WKY and lean littermates of SHR/NDcp. This effect was not observed with FO at a normal dose (5% in the diet). These results indicate that, in the context of the CYP profile, SHR/NDcp is an animal model that is suitable for studying MS and imply that FO intake is critical in determining the efficacy or adverse effects of drugs in patients with MS.

Fish oil affects the metabolic process of trimethylamine N-oxide precursor through trimethylamine production and flavin-containing monooxygenase activity in male C57BL/6 mice

“…Previous study suggested the intake of sh oil at a high dose up-regulated CYP3A2 gene expression and CYP3A activity in liver. 29 Fish oil was also proved to increase the activities of CYP1A1 and CYP3A1 containing drug-metabolizing capacity. 30 FMO was similar to cytochrome P450 (CYP) in the aspects including the location, co-factor requirement and activity toward xenobiotics.…”