Possible pharmacological effects of certain drugs on experimentally induced liver dysfunction in rats / Tarek Mohammed Mamdouh Abdelfatah Abdelghany ; Supervised Mostafa E. Elsayed , Amina S. Attia , Rania M. Abdelsalam

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Liver fibrosis results from chronic damage to the liver in conjunction with the accumulation of extracellular matrix proteins including collagen which is a characteristic of most types of chronic liver diseases. It has been revealed that AT - II induced contraction and proliferation of hepatic stellate cells (HSCs). Thus, the present study aimed to investigate the possible prophylactic and therapeutic effects of inhibiting RAS, especially angiotensin II (AT - II) using ACEI 2ramipril3 and angiotensin receptor type 1 (AT1 - R) blocker using irbesartan, on liver fibrosis induced by thioacetamide (TAA) in rats and comparing the results obtained with silymarin a known hepatoprotective and anti oxidant agent. Rats (n = 70) were classified into 7 groups (n= 10), normal control, fibrotic control and five fibrotic treated in which silymarin 100 mg / kg, p.o., ramipril 2.5 or 5mg / kg, p.o. or Irbesartan 2.5 or 5mg / kg, p.o. was given daily for 6 weeks. Liver fibrosis was induced by TAA (200 mg / kg, ip) twice per week for 6 weeks in all groups except in the normal control group. At the end of the 6th week blood samples were withdrawn from orbital sinus for measurement of plasma AST and ALT and animals were sacrificed and then livers were separated and homogenized for measurement of oxidative stress biomarkers (MDA, GSH and NOx), inflammatory markers (TNFÜ, IL10 and MPO) and a fibrotic marker (hydroxyproline). Furthermore, MMP- 13, TIMP- 1, Ü- SMA and collagen 1 gene expressions were estimated using RT - PCR and TGFÝ was estimated using western plot method

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