| Abstract: |
Part I: Liver fibrosis: The present investigation was carried out to clarify the role of TNF-α in the pathogenesis of liver fibrosis after repeated intraperitoneal administration of CCl4 (25 µl/100gm) 3 times weekly for 6 weeks and to evaluate the role of different TNF-α inhibitors such as captopril, pentoxifylline and Cordyceps sinesis in improving liver status through determination of the level of TNF-α, AST, ALT, ALP, proteins and lipid profile in addition to histopathological examination. The results obtained can be summarized as follows: 1- Administration of CCl4 to normal rats induced a significant elevation of TNF α, AST, ALT, ALP, cholesterol, triglycerides and LDL levels and a significant reduction in total protein, albumin, globulin and HDL levels compared to normal rats. Examined liver showed extensive necrosis of the hepatic cells, represented by cytoplasmolysis and pyknosis of the nuclei, together with moderate portal and perilobular fibrosis (30-40%). 2. Fibrotic rats left for four weeks after induction of fibrosis without treatment (fibrotic untreated group) showed a significant decrease in ALT, AST, ALP and TNF-α levels compared to fibrotc rats. On the other hand, the same group exhibited a significant increase in ALT, AST, ALP, TNF-α, cholesterol, triglycerides and LDL levels compared to normal group and a significant decrease in globulin and HDL levels compared to normal group. In addition, it didn’t produce any significant change in total protein and albumin levels compared to fibrotic and normal groups. Summary and Conclusion 3. Fibrotic rats treated with captopril (60 mg/kg, orally) for 30 days produced a significant reduction in ALT, AST, TNF-α, cholesterol, triglycerides and LDL levels. In addition, it caused a significant elevation in total protein, albumin, globulin and HDL levels compared to fibrotic untreated group. Liver of captopril treated fibrotic rats were apparently normal. Most lobules showed normal hepatic parenchyma with increased mitotic and regenerative attempts represented by active hepatic cells and large number of binucleated cells.
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