AMELIORIATION OF CHEMICALLY-INDUCED HEPATOCYTE INJURY BY CYCLOSPORINE A

Autor: Hassan Farghali, Kameníková L, Sixtus Hynie, J Martínek
Rok vydání: 1996
Předmět:
Zdroj: Pharmacological Research. 34:211-218
ISSN: 1043-6618
DOI: 10.1006/phrs.1996.0090
Popis: 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 −1 day −1 ). Six hours after the second dose, 1mlkg −1 of CCl 4 was 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 vivo produced 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 4 administration; (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.
Databáze: OpenAIRE
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