Abstract: Valproate (VPA) is a widely used anticonvulsant drugs; however, it represents a typical example of drug-induced adverse reactions especially liver injury. The polyunsaturated, omega-3 fatty acid, docosahexaenoic acid (DHA), prerogatives diverse cytoprotective effects, even though mechanism remains unclear. We have previously demonstrated a protective effect of DHA against VPA-induced hepatotoxicity. Therefore, this study was designed to investigate potential mechanisms of DHA in subsiding VPA-induced hepatotoxicity. To achieve this goal, three group of age matched male Sprague Dawley rats were used in the current study; control group, VPA-group received VPA alone (500 mg/kg orally ever day) and VPA+DHA group received VPA plus DHA …show more content…
DHA was purchased from Swanson Health Product, North Dokota, USA, as capsules; each provides 250 mg of pure DHA. DHA was diluted in corn oil, with equivalent amounts of oil given to all animals in the control group. Animals Studies All procedures with animals were performed in accordance with the Public Health Service Guide for the Care and Use of Laboratory Animals and Georgia Regents University guidelines. Twelve week old male Sprague Dawley rats were purchased from Harlan Laboratory and used in the current study. There group of rats were used in our study (n= 6–8 rats/group) as follows Control-group received vehicle (corn oil daily) for 2 weeks, VPA-group received VPA alone (500 mg/kg PO, daily) for two weeks and VPA+DHA-group received VPA (500 mg/kg PO, daily), followed by DHA (250 mg/kg PO, daily) for two weeks. After two weeks of treatment, rats were terminated using sodium pentobarbital (50 mg/kg, IP) for liver collection. Liver was isolated, weighed, aliguoted in few tubes and snap frozen in liquid nitrogen. A 10 % (w/v) liver homogenate was made in phosphate-buffered saline (PBS) (pH 7.4) for the assay of hepatic TBARs, NADPH, NrF2, and HO-1. Other frozen liver samples were homogenized in RIPA buffer for western blotting (n=4/group). A piece of liver was fixed in 10% formalin for histochemical evaluations of