اسم المؤلف:
اسماء عبد الوهاب احمد
اسم المشرف:
علي اسماعيل عبد الله محمد | خالد جمعه خليل
المستخلص:
تعرف السمنه ب ترسب الدهون وخاصه في منطقه البطن الذي يرتبط ارتباطا وثيقا بالنظام الغذئي الناجم عن مرض خطير مثل السكري , اضطراب الدهون في الدم وارتفاع ضغط الدم التي توثر على صحه الانسان. ميتفورمين له تاثير ايجابي على التغيرات الايضيه الناتجه عن السمنه. علا | Background : Obesity is defined as the deposition of fat, especially in abdominal regions, which is closely related to serious diet - induced diseases such as type2 diabetes, dyslipidemia, and hypertension that affect human health. metformin has favorable influence on metabolic changes induced by obesity. Furthermore; treatment with metformin has good hepatoprotective effects against fatty changes induced by high fat diet. Moreover, it's interesting to mention that canagliflozin has comparable therapeutic effects to metformin on obesity induced metabolic disturbance but, unfortunately, it has not significant therapeutic impact on obesity induced hepatic steatosis. Interestingly, it has been found in the present study that use of metformin and canagliflozin in combination has superior promising impact on obesity induced metabolic and pathological changes.Aim of the study : The present study investigated the influence of metformin, canagliflozin, & their combination on body weight, food intake, glycemic indices, insulin sensitivity, and lipid profiles in diet - induced obese mice Materials and methods : The animals were divided into two groups.The first group feed with normal chow served as normal group {n=10}. The second group feed with high fat diet serve as high fat diet group {n=40} for two and half months and after the induction of obesity, then further subdivides into four groups. Group I : still feed with normal chow serve as control group{n=10}. Group II : received no drug(s) but only feeding with high fat diet, which serves as high fat diet group{n=10}. Group III : received a single dose of canagliflozin {10 mg/kg/po}, daily for 4 weeks by gavage method serves as canagliflozin group{n=10}. Group IV : received single dose of metformin {300 mg/ kg, po}, daily for 4 weeks by gavage method serves as metformin group{n=10}. Group V : received single dose of both canagliflozin {10mg/ kg, po} and metformin{300mg/kg, po}, daily for 4 weeks by gavage method serves as combination group{n=10}.At the end of the study, blood samples were taken for biochemical analysis, then animals were sacrificed and livers were taken for histopathological examination. Results : Mice feeding with high fat calorie content 60% for two and half months showed a significant increase in body weight, food intake, glycemic indices, homeostasis model assessment - insulin resistance (HOMA - IR), fasting plasma insulin and lipid profiles with important histopathological alterations. While, treatment with metformin - canagliflozin combination elicited a significant decrease in the all study and biochemical parameters with significant histopathological changes characterized by complete improvement on hepatic tissues. In comparison to metformin treatment also showed significant decrease in all study & biochemical parameters with good protective effect against obesity - induced hepatic steotosis. Whereas, canagliflozin also showed a significant decrease in all study and biochemical parameters with no significant improvement on hepatic tissue but the main thing that observed with canagliflozin is a superior effect on body weight with respect to metformin.Conclusion : treatment with metformin - canagliflozin combination provides a significant hepatoprotective effects against fatty changes induced by high fat diet. Moreover, this combination has favorable influence on metabolic changes induced by obesity. Whereas, each drugs alone show good improvement on many parameters including body weight, glycemic indices, insulin sensitivity, and lipid profiles with better improvement of hepatic tissue associated with metformin in contrast to canagliflozin that shows no significant improvement in hepatic tissue but, the excellent reduction in body weight seen in canagliflozin with respect to metformin.
