الفهرس 
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Abstract
Non-alcoholic fatty liver disease (NAFLD) is a severe form of fatty liver disease unrelated to chronic alcohol consumption. It is becoming the most common cause for chronic liver disease. Non-alcoholic fatty liver disease encompasses a spectrum of disorders ranging from simple steatosis to non-alcoholic steatohepatitis (NASH) which is a risk factor for the development of cirrhosis and hepato-cellular carcinoma. There is currently no therapy that is of proven benefit for NAFLD & NASH. In fact, dietary interventions and physical exercise are known to be of limited effect. Hence, there is an urgent need for safe pharmacologic therapy that successfully reverses or prevents progression of liver injury and fibrosis in patients with NAFLD. Pharmacological approach acting upon one or more specific targets involved in NAFLD pathogenesis can be used such as antidiabetics, lipid lowering drugs and antioxidants.
In view of such consideration, the present study was designed to evaluate the protective effects of metformin, sitagliptin, vitamin E and selenium on the development and progression of fatty liver in a rat model induced by HFD.
The study was conducted on 48 male albino rats weighing 150-200 grams:
They were divided into six groups, each of eight rats:
III. Control group: Received 1ml gum acacia (2%) orally daily for 8 weeks. These animals were fed normal rat chow throughout the study.
IV. High fat diet group: (fatty liver): Fed with –in house prepared- HFD (58% calories as fat) throughout the study (8 weeks). They were further subdivided into the following groups:
- Group II a (High fat diet control group): Received 1ml gumacacia (2%) orally daily for 8 weeks.
- Group II b (Metformin treated group): Received Metformin orally in a dose of (37.5mg/kg) daily for 8 weeks.
- Group II c (Sitagliptin treated group): Received Sitagliptin orally in a dose of (10mg/kg) daily for 8 weeks.
- Group II d (Vitamin E treated group): Received vitamin E orally in a dose of (10IU/kg) daily for 8 weeks
- Group II e (Selenium treated group): Received Selenium orally in a dose of (0.2mg/kg) daily for 8 weeks.
Drugs and vehicle were administered orally by an oral gavage syringe. After 8 weeks, animals were anesthetized by ether and blood samples were collected for assessment of these parameters: fasting blood glucose (FBG), liver function test (ALT) and lipid profile (triglycerides and total cholesterol). The liver was dissected and divided into two parts, one part was homogenized, and the resulting supernatant was used for the assay of hepatic Nrf2 transcription factor level by ELISA kit. The other part of Liver biopsy dissected from rats was fixed in 10% formalin, routinely processed and embedded in paraffin. Tissue sections were subsequently stained with hematoxylin and eosin (H&E), and examined morphologically.