الفهرس 
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Abstract
Milestones have been achieved in the past thirty years in the understanding of liver fibrosis in humans. However, many aspects of fibrosis onset, progression and treatment remain to be elucidated. Hepatic inflammation and oxidative stress act as crucial players during the progress of liver fibrosis. Diabetes and its complications have been identified as one of the most serious public health threat worldwide, whose prevalence and economic impact are steadily growing. Oxidative damage to the tissues is shown to be the major contributor in the pathogenesis of diabetes and its associated complications. The unique antioxidant tannins and flavonoids contained in pomegranate and their antioxidant, anti-proliferative, anti-inflammatory and pro-apoptotic properties have recently drawn the attention of many scientists. Therefore, this study aimed to assess the effectiveness of pomegranate fruit extract (PFE) in alleviating thioacetamide (THIO)-induced liver fibrosis and streptozotocin (STZ)-induced diabetes mellitus in rats and to investigate the possible underlying mechanisms.
In the present study, Sprague Dawely (SD) rats were intraperitoneally (i.p.) injected with THIO (200 mg/kg, 3 times/week) for 6 weeks to induce liver fibrosis. PFE (150 mg/kg/day) was given orally from the first day. Treatment with PFE improved liver functions indicated by decreased serum AST and ALT levels while increased serum albumin. Moreover, PFE treatment improved liver/body weight index and decreased hydroxyproline and collagen contents, α-SMA expression and abnormalities in liver structure. Additionally, AGEs/RAGE activation, subsequently increased TGF-β1 and TIMP-1 levels and prominent oxidative stress induced by THIO were attenuated by PFE treatment.
Regarding the other model, SD rats were fasted for 16 hours then injected with a single dose of STZ (50 mg/kg, i.p.). PFE (150 mg/kg/day) oral treatment was initiated after 2 weeks of the STZ injection and was carried on continuously for 6 weeks. Daily treatment with PFE significantly improved STZ-induced changes in glycemic status, revealed by reductions in fasting blood glucose and HbA1C. Furthermore, kidney functions were partially corrected as indicated by decreased serum creatinine and BUN. Moreover, PFE treatment attenuated STZ-induced aortic and renal structural changes. Additionally, AGEs/RAGE activation, subsequently increased TGF-β1 concentration and prominent oxidative stress induced by STZ were attenuated by PFE treatment. Moreover, PFE improved STZ-induced impairment in relaxation response to ACh reflecting its potential to have protective role in STZ-induced diabetic complications.