To examine the effects of n-acetyl cystein, ascorbic acid and sirolimus on liver fibrosis due to experimental bile ducts ligation in rats by immunhistochemical, biochemical methods, light and electron microscopies.

Experimental bile duct ligation is used for to develop liver fibrosis. In several studies, prolonged bile duct obstructions caused liver fibrosis and cirrhosis was documented. The aim of the present study to examine the effects of n-acetyl cystein (NAC), ascorbic acid (vitamine C) and sirolimus (rapamycin) on liver fibrosis in bile duct ligated rats. 36 male Wistar-Albino rats were used and divided six groups; Controls, bile duct ligation (BDL) and four treatment groups; NAC, vitamine C, group, NAC + vitamine C, and rapamycin. Twenty-one days after ligation, rats were sacrified and liver and blood samples were taken. For light microscopy, liver tissues were stained hematoxylin and eosin, masson trichrome, periodic acid-Schiff (PAS) and immune labelling for ß catenin, Ki-67, ?-SMA, and desmin. Apoptosis was evaluated by TUNEL method. Ultrastructure of liver was examined in all groups. It was found that liver enzymes and blood bilirubine levels were increased in all groups except controls. In ligation group, bile duct proliferation, inflammatory cells, increased connective tissue, locking integrity in lobular borders and mitotic figures in hepatocytes were seen.NAC treatment increased proliferation when compared to ligation group. In rapamycin group, fibrosis, necrosis and proliferation, were diminished. Other treatment groups were similar to ligation group. ?-SMA immune labelled cells were increased in fibrotic regions of bile duct ligated rats. While rapamycin decreased intensity of ?-SMA immune labelling the other treatmens did not. Desmin immun reactivitive cells were found around necrosis areas and proliferated bile ducts. Their staining intensity was similar between ligation and treatment groups.There is no differenc ß-catenin labelling among the groups. Ki-67 immun labelling which show mitotic activity was increased epithelium of bile ducts and hepatocytes in ligation group. Treatment with rapamycin and NAC+ Vit C decreased Ki-67 labelling intensity.TUNEL (+) cells were seen in the liver parenchyma high density, but not in the proliferated bile ducts. Only rapamycin treatment caused TUNEL (+) cells in the proliferated bile ducts.In conclusion, rapamycin treatment reduced bile duct proliferation, fibrosis and necrosis in liver tissues of bile ducts ligated rats. Biochemical parameters were also corralated with histologic data.Key words: Bile duct ligation, liver fibrosis, NAC, vitamine C, rapamisin, apoptosis