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Abstract There are several factors lead to liver toxicity and diabetes namely the toxins such as aflatoxins, drugs in overdoses and chemicals such as heavy metals and organic solvents especially tetrachloride, STZ and alcohols. There are many herbals which are used in therapeutic or protective effect against diseases in rats. These herbals include rosemary herb and others. Rosemary is a perennial herb with fragrant, evergreen needle-like leaves and white, pink, purple or blue flowers native to Mediterranean region. In this thesis, alcoholic and aqueous extracts of rosemary and its oil were used to investigate their effects on diabetic and liver malfunction rats by administrating them with STZ or CCl4 respectively for three weeks. This study was achieved to evaluate (i) the therapeutic effects of alcoholic, aqueous and oil extracts of rosemary on acute hyperglycemia induced by streptozotocin in male rats. (ii) The protective effects of alcoholic, aqueous and oil extracts of rosemary on the liver toxicity induced by CCl4 in male rats. In order to achieve these objectives, the following biological experiments were carried out as follows: Effect of rosemary extracts on diabetic and liver malfunctional rats: Fifty four rats were used for the experiment. They were divided into 9 groups and each group consists of 6 rats. group (1) was fed only on the basal diet and served as the negative control group. The other groups received the different treatments besides feeding on the basal diet. group (2) was treated with STZ dissolved in 0.1M citrate buffer (pH 4.5) by a single intraperitonial injection at a dose of 50 mg/kg body weight and served as the positive diabetic control group. group (3), STZ induced diabetic rats, was treated with alcohol extract of Rosemary orally by stomach tube with a dose of (200mg/kg body weight) daily for 3 weeks. group (4), STZ induced diabetic rats, was treated with aqueous 69 SUMMARY Nada S.M. Elshaer (2018), M.Sc. Fac. Agric., Ain Shams Univ. extract of Rosemary orally by stomach tube with a dose of (200mg/kg body weight) daily for 3 weeks. group (5), STZ induced diabetic rats, was treated with Rosemary essential oil orally by stomach tube with a dose of (200mg/kg body weight) daily for 3 weeks. group (6) was treated with CCl4 dissolved in corn oil (50% v/v) by intraperitonial injection twice a week for 21 days at a dose of 1ml/kg body weight and served as the positive hepatitis control group. group (7), CCl4 induced hepatotoxicity, was treated with alcohol extract of Rosemary orally by stomach tube with a dose of (500mg/kg body weight) day after day for 3 weeks. group (8), CCl4 induced hepatotoxicity, was treated with aqueous extract of Rosemary orally by stomach tube with a dose of (250mg/kg body weight) day after day for 3 weeks. group (9), CCl4 induced hepatotoxicity, was treated with Rosemary essential oil orally by stomach tube with a dose of (250mg/kg body weight) day after day for 3 weeks. The adverse effects of CCl4 and streptozotocin compared to the protective and therapeutic effects of these plant extracts were monitored through determination of different blood biochemical assays (i.e. AST, ALT, ALP, fasting blood glucose, postprandial glucose, total protein, albumin, triglycerides, total cholesterol, HDL and LDL) and histological examinations of liver tissues for CCl4 groups and pancreas for STZ groups. The obtained results can be summarized as follows: A- Therapeutic effect of (alcoholic, aqueous and oil) extracts of Rosemary plant on the acute hyperglycemia induced by streptozotocin in rats: There were slight increase in the levels of fasting and postprandial blood glucose for the positive control, and gradual decrease for diabetic rats treated with alcoholic, aqueous and oil extracts of rosemary during three weeks. The alcoholic extract of rosemary was found to have therapeutic potential. It possesses hypoglycemic properties but the aqueous and oil extracts of rosemary were more efficient, (restoring the 70 SUMMARY Nada S.M. Elshaer (2018), M.Sc. Fac. Agric., Ain Shams Univ. levels of fasting and postprandial blood glucose to their normal ranges after 21 days). B- Therapeutic effect of alcoholic, aqueous and oil extracts of rosemary plant on Triglyceride (TG), total cholesterol (TC), (HDL) and (LDL): The serum lipid parameters triglyceride, total cholesterol and LDL in the STZ diabetic rats increased while HDL decreased in comparison with negative control group, since it amounted in rats administrated alcoholic extract and aqueous extract of rosemary (46.1 and 49.8 mg/dl respectively). There is significant difference between these two groups and the control one. However the HDL in group administrated rosemary oil is amounted (55.1 mg/dl) and this amount is significantly higher than both positive control (42.2 mg/dl) and negative control (51.3 mg/dl). C- Protective effect of Rosemary extracts on the liver toxicity induced by CCl4 in rats: 1. Effect of alcoholic, aqueous and oil extracts of rosemary on the liver functions in rats treated with CCl4: 1.1. Serum alanine aminotransferase (ALT) activity: The difference between both (negative and positive control) and the activity of ALT in the rats treated by alcoholic and aqueous extracts of rosemary is significant. The protective effects of the plant extracts against liver toxicant occurred by decreasing the activities of this enzyme. The alcoholic and aqueous rosemary extracts weren’t restored to the normal values. However the oil extract was restored to its normal control. i.e. the difference between positive control and ALT in rats treated by rosemary oil is not significant. 1.2. Serum aspartate aminotransferase (AST) activity: The difference between both (negative and positive control) and the activity of AST in the rats treated by alcoholic and aqueous extracts of rosemary is significant. The protective effects of the plant extracts against liver toxicant occurred by decreasing the activities of this enzyme. The alcoholic and aqueous rosemary extracts weren’t restored to the normal 71 SUMMARY Nada S.M. Elshaer (2018), M.Sc. Fac. Agric., Ain Shams Univ. values. However the oil extract was restored to their normal control. i.e. the difference between positive control and AST in rats treated by rosemary oil is not significant. 1.3. Serum alkaline phosphatase (ALP) activity: There is no difference recorded between (negative and positive control) and (aqueous and alcoholic) treatments. The protective effects of the plant extracts against liver toxicant occurred by decreasing the activities of this enzyme. The alcoholic and aqueous rosemary extracts weren’t restored to the normal values. However the oil extract restored to their normal control. The difference between positive control and ALP in rats treated by rosemary oil is not significant. 1.4. Serum protein: The data showed no significant (p ≤ 0.05) differences among the levels of serum total protein and serum albumin for the rats received the different treatments compared to the negative and positive controls. 2. Effect of alcoholic, aqueous and oil extracts of rosemary on the serum lipid profile in rats treated with CCl4: There were no significant (p ≤ 0.05) differences in the levels of serum triglycerides, total cholesterol, HDL and LDL for the rats received the rosemary extracts (alcoholic, aqueous) and its oil compared to the negative control. Effect of alcoholic, aqueous extracts and oil rosemary on the histological investigations of pancreas in rats treated with STZ: Histological examinations of pancreas of rats from the negative control group revealed the normal histological structure of pancreatic parenchyma. In contrary, pancreas of rats treated with STZ showed vacuolation of epithelial lining pancreatic acini and vacuolation of cells of islets of Langerhan‘s. The rats treated with STZ plus alcoholic extract of rosemary don’t have histopathological changes noticed in pancreas. Examined sections from rats treated with STZ plus aqueous extract of rosemary showed no changes except congestion of pancreatic blood 72 SUMMARY Nada S.M. Elshaer (2018), M.Sc. Fac. Agric., Ain Shams Univ. vessel. However, pancreas of rats treated with STZ plus rosemary oil revealed no histopathological changes. Effect of alcoholic, aqueous extracts and oil rosemary on the histological investigations of liver in rats treated with CCl4: Histological examinations of liver tissues liver of rats from the negative control group revealed the normal histological structure of hepatic lobule. Moreover, liver of rats treated with CCl4 revealed fibroplasia in the portal triad, cystic dilatation of bile duct, fibroblasts proliferation between the hepatic lobules. Meanwhile, liver of rats treated with CCl4 plus alcoholic extract of rosemary showed slight activation of Kupffer cells, with congestion of central vein and hepatic sinusoids. Moreover, examined liver of rats treated with CCl4 plus aqueous extract of rosemary revealed Kupffer cells activation, fibroblasts proliferation between the hepatic lobules, cytoplasmic vacuolation of hepatocytes and focal mononuclear cells infiltration. However, liver of rats treated with CCl4 plus rosemary oil showed slight activation of Kupffer cells, slight fibroplasia in the portal triad and slight cytoplasmic vacuolation of some hepatocytes |