Objective:To explore the protective function of L-carnitine against valproate-associated hepatotoxicity in infant rats and its mechanism.Methods:Rat models with VPA liver lesion were established by oral administration of VPA and PB.L-carnitine was adopted as intervention measure:to observe its protection of experiment rat livers

especially the function of liver mitochondrion.Levels of plasma ammonia

L-carnitine and coagulation factors in sera as well as the changes of respiratory enzymes in hepatic mitochondria were measured by chemical colorimetry. Mitochondrial membrane potential(MMP)

and VPA and PB blood drug levels in liver were determined by flow cytometer and HPLC

respectively.and morphological changes of hepatocytes were observed under microscope with Oil-Red-O staining.Results(1)In the groups affected by VPA or VPA added with PB

the activities of SDH and CCO significantly decreased compared with control group(P<0.01);While activities of SDH and CCO were effectively protected by L-carnitine;(2)MMP was reduced by 21.47% in infant rats treated with VPA added with PB

Which was significantly different from control group(P<0.05).This reduction could be effectively reversed by L-carnitine;(3)In all rats treated with VPA added with PB

there were significant abnormalities in function of blood coagulation and serum fibrinogen

especially reflected on the content change of clotting factors PT、TT、APTT and Fbg

and the levels of plasma ammonia and L-carnitine also changed significantly. Furthermore

compared with controls

no alteration of coagulation function and ammonia levels in blood had been found since L-carnitine supplementation;(4)Oil-Red-O staining showed that significant lipid vacuoles primarily occurred in periportal areas of liver lobule in rats treated with VPA or VPA added with PB. The number of hepatocyte containing lipid droplets in infant rats was 9.2 times higher than that in control

and 15.7 times higher than that in VPA added with PB group. The difference was significant(P<0.01).These indicated that lipid droplets in liver cells induced by VPA could effectively prevented with coadministration of L-carnitine.Conclusion:Protective effects of L-carnitine against VPA-associated hepatotoxicity were well demonstrated in the study

which might be achieved by preventing the formation of lipid droplets in hepatocyte and protecting the function of mitochondria. In addition

VPA serum levels may not be high because of the coadministration with liver enzyme inducers

but we still should pay more attention to its hepatotoxicity especially in infant because of its incompleted substrata.