Curcumin Affords Protection against Valproic Acid Induced Teratogenicity by Curtailing Oxidative Stress and Inhibiting CYP2C9 activity

Abstract

Administration of drugs during pregnancy is always done with immense caution however, multiple neurological ailments including epilepsy and depression warrant medical treatments even during pregnancy. This exposes unborn fetus to killer teratogenic effects, thus warranting intense studies towards finding potential anti-teratogenic agents. We employed valproic acid (VPA) induced model of fetotoxicity and teratogenicity in rats towards assessing the antiteratogenic activity of curcumin, an antioxidant well known for attenuating oxidative stress by increasing the content of glutathione and reducing the level of lipid hydroperoxide. We studied the level of GSH, catalase, SOD, ROS, TBARS and activities of CYP2C9 and figured that VPA at the dose of 300 mg/kg body wt. significantly decreased the GSH, SOD, catalase and increased the levels of ROS, TBARS, mRNA expression and levels of CYP2C9 enzyme which is involved in the formation of toxic metabolite (E)-2,4-dieneVPA. Upon co-administration of curcumin (100,150 and 200 mg/kg body wt.) along with VPA the levels of GSH, SOD, catalase exhibited significant increase and ROS, TBARS, mRNA expression and level of CYP2C9 enzyme were found to be significantly decreased with respect to VPA. We conclude that the toxic metabolite (E)-2,4-dieneVPA is involved in generation of oxidative stress subsequently contributing in induction of malformations and anomalies and that curcumin affords dose dependent amelioration of the anomalies exerted by VPA. Our studies are suggestive of the fact that curcumin has antioxidant activity and can curtail the formation of toxic (E)-2, 4-dieneVPAby inhibiting CYP2C9 enzyme and finally protecting fetuses in dose dependent manner.