Objective To study the protection and mechanism of co-administration of vitamin E with coenzyme Q10(CoQ10) to valproate-associated
hepatotoxicity in infantal rats.Methods The rat models were established by oral administration of
valproic acid(VPA) in ablactation(21 days) Wistar rats,at doses of 500 mg/(kg·d) during 30 days,other groups received the same amount of VPA with phemobarbitone(PB) and co-administration with vitamin E and CoQ10.The changes of liver cell morphology and the blood coagulation test,as well as the contents of succinic dehydrogenase(SDH),cytochrome oxidase(CCO),cytochrome,the levels of glutothione(GSH) and malondial dehyde(MDA) in rat liver mitochondria were detected by chromatometry,HPLC,Oil-Red-O staining and electron microscope,respectively.Results 1.Average content of cytochrome aa3 in liver mitochondria of infantal rats were reduced by 58.80% and(61.80%) because of administration of VPA and VPA added with PB.The protection against the loss of cytochrome aa3 by coadministration of VitE and CoQ10 was obvious.As for activities of SDH and CCO,which affected by VPA and VPA added with PB in rats,were significantly lowered compared with control group(P<0.01).However activities of SDH and CCO were effectively protected by coadministration with VitE and CoQ10;2.In all rats received with VPA and PB,there were significant abnormalities in function of blood coagulation and serum fibrinogen were shown.Furthermore,liver coagulation function was effectively protected with VitE and CoQ10 from VPA added with PB;3.Compared with control group,levels of glotathione-SH(GSH) in liver mitochondria were significantly decreased in infantal rats treated with VPA or added with PB(P<0.01),whereas the levels of malondialdehyde(MDA) were significantly increased in infantal rats(P<0.05).The levels of GSH and MDA in mitochondria were still normal in rats which treated with VitE and CoQ10;4.Significant lipid vacuoles primarily occurred in periportal areas of liver lobule in infantal rats received with VPA or and VPA added with PB on frozen sections stained with Oil-Red-O,and the numbers of hepatocyte contained lipid droplets in infant rats was 9.2 times higher than that in control rats,15.7 times higher in VPA added with PB group,and there was significant difference statistically between them,respectively(P<0.01).It were indicated that lipid droplets in liver cells induced by VPA could partly prevented with coadministration of VitE+CoQ10,and the lipid droplets also was confirmed by electron microscopic examination.Conclusion Antioxidant are effective in treating VPA-associated hepatotoxicity.