Early sequential hepatic changes in fulvine treated rats

ABSTRACT

The purpose of this experiment was to study the early structural and functional hepatic changes occurring in rats treated with a standardized dose of fulvine by gastric intubation. Histologic observationas and biochemical determinants were done at 1, 3, 6, 9, 18 and 32 hours after treatment. The results indicated that fulvine induced a wide spectrum of hepatic lesions that were detected as early as one hour after its administration. Some of the earliest lesions, such as the deterioration of hepatocytic endoplasmic reticulum and of the nuclei, progressed with time and suggested that the hepatocytes, rather than the vascular structures were the primary site of attack. Although single hepatocytic necrosis was detected at 3 hours and was only observed at the latest period (32 hours). This zonal necrosis was preceded by a prominent and progressive hepatocytic swelling in periportal and centrolobular areas and by increasing accumulation of cell debris and blood elements in the sinusoids. While fulvine or its metabolities appears to exert a direct necrotizing effect on the hepatocytes, the microcirculatory changes observed in our previous studies and suggested by the ultrastructural findings in the present one, may offer an explanation for the preferential location of the lesions that precede the occlusion of the terminal hepatic venules. (AU)