Pathomorphological oranges in mouse liver and kidney during prolonged valproate administration

Mice given sodium valproate 0.71% weight/volume in drinking water for 7, 14 and 21 days were assessed for pathomorphological changes in liver and kidn ey tissues at certain time points. This treatment caused a marked alteratio n in liver and kidney cell morphology which was proportional to the period of treatment. This treatment induced fatty degeneration of hepatocytes, inc reased the number of Kupffer cells and caused them to swell. These changes were irregular after days 7 and 14 of treatment but with time increased in intensity, producing inflammation of the portal tracts, albuminous degenera tion and necrosis of septa. Precirrhotic conditions, cirrhosis, acidophilic degeneration of hepatocytes and glassy eosinophilic homogenous cytoplasm w ere a constant feature after 21 days' treatment. In some cases the portal a rea was invaded by small, round inflammatory cells. Hepatocytes in this gro up were swollen, with large nuclei and increased amounts of condensed chrom atin. The kidney sections of the same animals revealed severe morphological changes, indicated by significant epithelial necrosis and sloughing of tub ules, as well as cast formation and mild lymphocytic infiltrate after 21 da ys' treatment. The results suggest that the histopathologic changes induced by sodium valproate are dependent upon the duration of exposure of these o rgans to the drug. Prolonged use of this drug should be carefully assessed.