Curcumin affords protection against valproic acid induced teratogenicity by curtailing oxidative stress and inhibiting CYP2C9 activity
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 the unborn fetus to killer teratogenic effects, thus warranting intense studies towards finding potential anti-teratogenic agents. We employed a 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 the activities of CYP2C9 and determined that VPA at a dose of 300 mg kg−1 body wt significantly decreased the levels of GSH, SOD and catalase and increased the levels of ROS, TBARS, mRNA expression and the levels of the CYP2C9 enzyme which is involved in the formation of the toxic metabolite (E)-2,4-diene-VPA. Upon co-administration of curcumin (100 150 and 200 mg kg−1 body wt) along with VPA the levels of GSH, SOD and catalase exhibited a significant increase and ROS, TBARS, mRNA expression and the level of CYP2C9 enzyme were found to be significantly decreased with respect to VPA. We conclude that the toxic metabolite (E)-2,4-diene-VPA is involved in the generation of oxidative stress subsequently contributing in the 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-diene-VPA by inhibiting the CYP2C9 enzyme and finally protecting fetuses in a dose dependent manner.