AMELIORIATION OF CHEMICALLY-INDUCED HEPATOCYTE INJURY BY CYCLOSPORINE-A

Cyclosporine A, beside its current applications, possesses potential h epatoprotective effects. This study was directed to investigate the ef fect of Cyclosporine A pretreatment on hepatic injury due to carbon te trachloride (CCl4) and D-galaclosamine. Rats were injected by two succ essive doses of Cyclosporine A (5 mg kg(-1) day(-1)). Six hours after the second dose, 1 ml kg(-1) of CCl4 was administered i.p. Effects ass ociated with Cyclosporine A pretreatment were examined by using isolat ed hepatocytes and hepatocytes that were immobilized and continuously perfused. D-Galactosamine (5 mM) was added directly to the perfusion m edium. After isolation, hepatocytes were examined histologically by li ght and electron microscopy, immobilized and perfused for further meta bolic functional activity evaluation. Cyclosporine A pretreatment in v ivo produced hepatoameliorative effects of various degrees which were statistically significant as manifested by: (1) an increased trypan bl ue exclusion after CCl4; (2) an improved ureagenesis after CCl4; (3) a reduction in the lipid droplets accumulation in the cytoplasm produce d by CCl4 administration; (4) well preserved cytoplasmic organelles as mitochondria, endoplasmic reticulum ER, nuclear chromatin structures that were altered by CCl4 and (5) an increased hepatocytes survival in the agarose gel matrix, reduction of LD leakage and improvement of ur eagenesis after D-galactosamine addition to the perfusion medium. The beneficial effect of Cyclosporine A pretreatment in modifying hepatoto xicity of chemical insults merits further studies. (C) 1996 The Italia n Pharmacological Society.