AMELIORIATION OF CHEMICALLY-INDUCED HEPATOCYTE INJURY BY CYCLOSPORINE A

Abstract

Cyclosporine A, beside its current applications, possesses potential hepatoprotective effects. This study was directed to investigate the effect of Cyclosporine A pretreatment on hepatic injury due to carbon tetrachloride (CCl 4) and D-galactosamine. Rats were injected by two successive doses of Cyclosporine A (5mgkg −1day −1). Six hours after the second dose, 1mlkg −1of CCl 4was administered i.p. Effects associated with Cyclosporine A pretreatment were examined by using isolated hepatocytes and hepatocytes that were immobilized and continuously perfused. D-Galactosamine (5m M) was added directly to the perfusion medium. After isolation, hepatocytes were examined histologically by light and electron microscopy, immobilized and perfused for further metabolic functional activity evaluation. Cyclosporine A pretreatment in vivoproduced hepatoameliorative effects of various degrees which were statistically significant as manifested by: (1) an increased trypan blue exclusion after CCl 4; (2) an improved ureagenesis after CCl 4; (3) a reduction in the lipid droplets accumulation in the cytoplasm produced by CCl 4administration; (4) well preserved cytoplasmic organelles as mitochondria, endoplasmic reticulum ER, nuclear chromatin structures that were altered by CCl 4; and (5) an increased hepatocytes survival in the agarose gel matrix, reduction of LD leakage and improvement of ureagenesis after D-galactosamine addition to the perfusion medium. The beneficial effect of Cyclosporine A pretreatment in modifying hepatotoxicity of chemical insults merits further studies.