Modulation of Arachidonic Acid Metabolism in the Rat Kidney by Thymoquinone: Implications for Regulation of Blood Pressure

Abstract

BackgroundWe investigated the effects of thymoquinone (TQ), a Quinone phytochemical in the plant Nigella Sativa, on Arachidonic acid (AA) metabolism in the kidney and its effect on arterial blood pressure, using spontaneously hypertensive rats (SHR) as our animal model system.MethodsRats were treated for 7 weeks with TQ (10, 20, or 40 mg/kg) added to their drinking water; drinking water alone was used as our control. Mean arterial pressure (MAP) was measured at 7‐day intervals throughout the study. At the end of the treatment, rats were euthanized, followed by preparation of kidney microsomes to measure the activity (using LC/UV and fluorescence assay) and expression (using immunoblotting) of enzymes involved in regulation of vasoactive metabolites: CYP4A, the key enzyme in the formation of 20‐hydroxyeicosatetraenoic acid, and the soluble epoxide hydrolase (sEH), which is responsible for the degradation of the vasodilator metabolites such as epoxyeicosatetraenoic acids.ResultsWe found that treatment with TQ leads to significant reductions in both the expression and activity of renal CYP4A isozyme. Only the high dose TQ resulted in a significant reduction in the expression and activity of renal sEH. Consistent with these data, we have found that treatment with TQ resisted the progressive rise in MAP in the developing SHR in a dosedependent manner.ConclusionThis is the first demonstration that TQ modulates the metabolism of AA by both kidney P450 enzymes and sEH in SHR rats. This may represent a novel mechanism by which TQ protects SHR rats against the progressive rise in blood pressure.Support or Funding InformationPacific University Research Incentive GrantMedical Research Foundation of OregonThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.