تاثير استخدام عقار النكلوزمايد بالمقارنة مع عقار المتفورمين على وزن الجسم ومؤشرات السكر في السمنة المحدثة عند الفئران == Effects Of Use Of Niclosamide Drug In Comparison With Metformin Drug On Body Weight And Glycemic Indices In High Fat Diet Induced Obese Mice
Author name:
خالد دهان صليبي
Supervisor name:
علي اسماعيل عبد الله محمد | خالد جمعة خليل
General topic:
Medicine
Specific topic:
Medicines and Toxins
Degree:
Master
University:
Mustansiriyah University - Faculty Of Medicine - Pharmacology Department
Language:
English
University location:
Baghdad
First pages:
19T1180 - p.pdf
Abstract:
في ستينيات القرن الماضي كان هناك نوع من العلاجات تستخدم للسيطرة على وزن الجسم او لتخفيفه , تلك المواد تعمل على تثبيط عضيات المايتوكوندريا من انتاج الطاقة وتحويل مجرى تفاعلات الاكسدة نحو انتاج الحرارة بدلا عن الطاقة وبذلك تحفز من زيادة اكسدة الشحوم ومادة ا | Background : Obesity is a state of excessive accumulation of fat tissue in the body , increasing energy expenditure is good way to manage obesity and the related complications. Mitochondrial uncouplers increase energy expenditure , they used before for weight controlling programs because these compounds uncouple mitochondria from generating ATP , moreover stimulate lipid and glucose oxidation preventing lipid accumulation in excess caloric intake conditions specially. Niclosamide an old drug introduced in 1960s as anthelmintic and had FDA approval for the treatment of most of tapeworm infections. It is well known mitochondrial uncoupler.Aim of the study : The present study aimed to investigate the influence of trial of the use of niclosamide in comparison to effect of metformin and their combination on body weight , glycemic indices and lipid profile in high fat diet induced obese mice.Materials and methods : The animals firstly divided to two groups one fed with normal regular mouse chow (30 mice) and the 2nd fed with high fat diet (60%kcal) for 2.5 months(100 mice) 10 mice from each group sacrificed at beginning of study represent baseline values and another 10 mice from each group sacrificed after 2.5 months to assess effect of high fat diet on study parameters. The group that fed with high fat diet further subdivided to 4 groups after 2.5 month of high fat diet feeding each 20 mice , 10 mice from each group sacrificed before treatment represent pretreatment values. Before treatment there are 5 groups assigned as group 1 fed normal regular mouse chow till the end of study , group 2 fed high fat diet without treatment till the end of study , group 3 fed with high fat diet till the end of study and treated with niclosamide for one month (150mg/kg) after obesity induction by high fat diet , group 4 fed with high fat diet till the end and treated by metformin (300mg/kg) for one month and finally group 5 fed with high fat diet till the end of study and treated by combination of niclosamide and metformin (150mg/kg , 300mg/kg respectively). blood samples taken from tail vein to evaluate the study parameters at baseline and after obesity induction by high fat diet (after 2.5 months) and after treatment ,then animals were sacrificed and livers were taken for histopathological observations.Results : The results of this study shown that the animals fed with high fat diet show metabolic disturbances manifested by significant increase (P < 0.05) in body weight , fasting insulin & fasting plasma glucose. Lipid profile show significant changes (P < 0.05)(cholesterol , triglycerides ,low density lipoproteins increased while high density lipoproteins decreased ) as compared to control group. High fat diet group also show impaired glucose tolerance , impaired insulin sensitivity and obvious liver structural changes manifested by sever steatosis.Treatment with niclosamide show improvement in all metabolic disturbances induced by obesity ; body Weight , fasting insulin and fasting plasma glucose reduced significantly (P < 0.05). Lipid profile parameters improved ; cholesterol , triglycerides , low density lipoproteins reduced significantly (P < 0.05) by one month treatment with niclosamide and high density lipoproteins increased significantly (P < 0.05) as compared to their baseline values before treatment, Glucose and insulin tolerance improved. It is nice to mention the influence of niclosamide in this study was comparable to metformin in all evaluated parameters.Combination of both drugs show favorable improvement in metabolic disturbances induced by obesity rather than each drug when used alone specially on liver histopathological changes.Combination of both drugs show significant reduction (P < 0.05) in body weight ,fasting plasma glucose and fasting plasma insulin. Lipid profile parameters improved significantly (P < 0.05) , glucose and insulin tolerance improved.Liver histopathological changes ameliorated to higher extent and become the closet to normal liver tissue morphology.Conclusions : The result suggest niclosamide have good antidiabetic action and can ameliorate the metabolic changes induced by obesity significantly. Its action is comparable to that of well known antidiabetic drug metformin. Niclosamide has favorable effect on body weight and can reduce body weight. Its combination with metformin show better improvement in metabolic disturbances induced by obesity and it has very good hepatoprotective effect against liver histopathological changes induced by high fat diet.
