الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide; especially in developing countries and it is closely associated with obesity, insulin resistance, diabetes, dyslipidemia and coronary artery diseases; all of which are manifestations of the metabolic syndrome. The pathophysiology of NAFLD is complex and may involve genetic factors, gut-derived microbial components, lipotoxicity and inflammation, which may occur either in the liver or in other tissues such as adipose tissue the gastrointestinal tract.
Extensive previous research in the last few decades proved that the pathogenesis of NAFLD is mediated by systemic and local inflammation. TNF-α is the main inflammatory mediator and is considered a key factor in the development of NAFLD in both humans and animals. Also, it is believed that the anti-inflammatory cytokine IL-25 is an important element in maintaining lipid metabolic homeostasis in the liver and negatively regulates the production of inflammatory mediators where its level decreases during acute and chronic liver injuries. This study was designed in order to investigate the changes in serum levels of bio-chemical and immunologic parameters as well as changes in hepatic lipid content during experimental induction of NAFLD using HFD model. Also, the study aimed at exploring the immune modulatory effects of variable doses of Pomegranate peel extract on the interplay between pro- and anti-inflammatory mediators under study as well as correlations with biochemical parameters.
To achieve this aim, this study conducted on 60 male Albino Wistar rats of approximately 150-170 grams weight and 2-3 months age. Rats were divided into two groups Group; a negative control group fed a standard diet and a NAFLD group fed a high fat diet (HFD) for 14 weeks. NAFLD rats were further subdivided according to PPE treatment into a positive control group that received normal saline instead of PPE in contrast to 3 subgroups that received PPE at concentrations of 50, 100 and 150 mg/kg body weight; each for 4 weeks. Finally, a NAFLD group was treated with DMSO (the organic solvent of crude PPE; the Vehicle group). PPE treatment was carried out daily by rat oral gavage for 30 days.
After the end of treatment all rats were sacrificed by cervical dislocation to obtain blood for assessment of liver function tests, glucose, insulin, insulin-resistance index, lipid profile, TNF-α and IL-25. Also, rats were dissected to obtain livers that were used for assessment of hepatic lipid content.
Concerning liver function parameters, NAFL rats showed significant elevation of serum levels of ALT, AST, GGT and total bilirubin. At the glucose homeostasis level, NAFL rats showed significant elevation in fasting glucose, insulin and the estimated HOMA-IR. These elevations in glucose homeostasis parameters were accompanied with significant abnormalities in the lipid profile manifested by increased TG, TC and LDL-C and decreased HDL-C comparing to control rats. Also, NAFLD rats had significantly elevated serum levels of TNF-α associated with significant decline in serum level of IL-25.
Upon PPE treatment, a significant and dose-dependent improvement in liver function parameters was recorded in NAFLD rats compared to positive controls. This was accompanied with ameliorated glucose, insulin and estimated HOMA-IR. PPE treatment also restored the disturbed lipid profile parameters as well as hepatic content where serum TG, TC, LDL-C, HHL-C and hepatic (TG and TC) were almost normalized relative to untreated NAFLD rats. Administration of PPE resulted also in a significant ameliorating effect on hepatic lipid content. Finally PPE treatments caused a significant decrease in serum TNF-α associated with restored serum level of IL-25. All these modulations were statistically significant and in a dose dependent manner.
from this study we can conclude that, PPE can be candidate for protective and therapeutic approach against obesity and its related diseases including NAFLD.