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العنوان
Protective effect of grape seed extract with selenium ”In Nano Form” and a sulfonylurea drug on the alterations of oxidative stress in experimentally diabetic irradiated rats /
المؤلف
Abdel Alim, Rasha Mohamed Ahmed.
هيئة الاعداد
باحث / رشا محمد أحمد عبد العليم
مشرف / ميرفت السيد عسكر
مشرف / سهام حسن محمد
مشرف / ميرفت السيد عسكر
الموضوع
selenium- therapeutic use. sulfonylurea. oxidative stress - pvevention.
تاريخ النشر
2017.
عدد الصفحات
V.P :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
العلوم الصيدلية
الناشر
تاريخ الإجازة
1/1/2017
مكان الإجازة
جامعة الزقازيق - كــليـــة الصيدلــــة - department of Biochemistry
الفهرس
Only 14 pages are availabe for public view

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from 196

Abstract

Ionizing radiation is known to produce a wide variety of biological effects in the living systems. These effects are in general enhanced in the presence of molecular oxygen. Excessive active oxygen produced in vivo is toxic and causes cell and tissue injures, including various pathological conditions.
Diabetes mellitus (DM) is a pathologic conditions resulting in severe metabolic imbalances in many tissues. Various studies have shown that diabetes mellitus is associated with oxidative stress, leading to:
1) An increased production of (ROS),
2) Reduction of antioxidant defense system.
The present study was carried out:
1. Evaluate the protective role of selenium nano particles-grape seed extract (SeNps- GSE) mixture in ameliorating the alterations in the oxidative stress biomarkers and restoring the endogenous enzymatic and non-enzymatic antioxidant activities as well as glucose homeostasis in diabetic rats exposed to gamma radiation.
2. Compare the protective effect of this mixture with the hypoglycemic sulfonylurea drug (glimepiride).
To fulfill such objectives, the following Parameters were selected to be studied:
Biochemical parameters:
1- In serum:
Serum glucose, Serum insulin as well as calculation of insulin resistance and serum total antioxidant capacity (TAC).2- In Liver tissue homogenate:
 Activities of the enzymatic antioxidant in liver tissue homogenate:
A. Catalase (CAT).
B. Superoxide dismutase (SOD).
C. Glutathione peroxidase (GPX).
 Estimation of the extent of lipid peroxidation (determined as thiobarbituric acid reactive substance ]TBARS [ ).
 Activities of non-enzymatic antioxidants in liver tissue homogenate:
A. Vitamin C.
B. Vitamin E.
Histopathological examination of liver and pancreas tissues were also performed.
Experimental design:
After two weeks acclimatization, rats were rendered diabetic by a single intraperitoneal (i.p) injection of STZ (45 mg/kg BW). After one week of administration, rats exhibiting blood glucose levels 200 – 270 mg/ dl were included in the study.
The selection of (SeNPs - GSE) mixture dose in this study was based on preliminary experimental trials and the selected dose was (Se 6.7 μg/kg + GSE 110.7 mg/kg).
Eighty normal and diabetic male albino rats were assigned into the following experimental groups for 2 weeks, each group consists of eight animals (n=8):
 group 1: Normal control group: Animals treated orally with saline for 14 days.
 group 2 :( Diabetic control group): Rats were made diabetic by a single i.p injection of STZ (45 mg/kg BW). group 3: Irradiated control group (Irr): Rats were received saline as group (1) and on day14 rats were submitted to a single dose of whole-body γ- radiation (4Gy).
 group 4: (Diabetic + Irradiation) control group: Rats were received the same dose of STZ as group (2) and on day14 rats were submitted to a single dose of whole-body γ- radiation (4Gy).
 group 5: (Nano mixture group): Normal rats were treated orally by (SeNPs - GSE) mixture for 14 consecutive days.
 group 6: (Nano mixture + Irradiation group): Normal rats were treated orally with (SeNPs - GSE) mixture for 14 consecutive days, on day 14 rats were irradiated (4Gy).
 group 7: (Drug + Irradiation group): Normal rats were treated orally with glimepiride (1mg/kg) as reference drug for 14 consecutive days, on day 14 rats were irradiated (4Gy).
 group 8: (Diabetic + Nano mixture group): Diabetic rats received (SeNPs - GSE) mixture for 14 consecutive days.
 group 9: (Diabetic + Nano mixture + Irradiation group): Diabetic rats received (SeNPs - GSE) mixture for 14 consecutive days then on day 14, rats was exposed to γ- radiation (4Gy).
 group 10: (Diabetic + Drug + Irradiation group): Diabetic rats were administered glimepiride (1mg/kg) for 14 consecutive days, on day 14 rats were irradiated (4Gy).
The main findings of the present study can be summarized as follow:-
1- Effect of diabetes on normal control group:
Induction of diabetes to normal rats by STZ (45 mg/kg i.p) leads to significant increase in serum glucose level accompanied by a significant decrease in serum insulin level, no significant difference in insulin resistance, significant decreasein serum TAC accompanied by significant increase in liver MDA level and significant decrease in liver CAT, SOD, GPx, Vit.C and Vit.E contents as compared to normal values.
2- Effect of γ- radiation on normal control group:
Exposure of normal rats to whole body gamma radiation (4Gy) significantly increase serum glucose level with a significant decrease in serum insulin, insulin resistance and serum TAC levels. There was a significant increase in liver MDA level and significant decrease in liver CAT, SOD, GPx, Vit.C and Vit.E contents as compared to normal values.
3- Effect of diabetes and γ- radiation on normal control group:
Exposure of diabetic rats to whole body gamma radiation (4Gy) significantly increase serum glucose level with a significant decrease in serum insulin level, insulin resistance showed insignificant effect. There was a significant decrease in serum TAC, significant increase in liver MDA level and significant decrease in liver CAT, SOD, GPx, Vit.C and Vit.E contents as compared to normal values.
Treatment of normal control rats with (45mg/kg b.w STZ) showed pancreatitis in pancreas tissue; while exposure to whole body gamma radiation (4Gy) showing hypertrophy and vacuolation of B cells of islets of Langerhans; moreover, by treatment of rats with (45mg/kg b.w. STZ) then exposed to whole body gamma radiation (4Gy) showing vacuolation of B cells of islets of Langerhans.
Histopathological examination revealed that, Treatment of liver tissue of normal control rats with (45mg/kg b.w STZ) showed progressive dilatation of hepatic sinusoids; Whole body gamma irradiation (4Gy) showing vacuolization of hepatocytes and portal infiltration with leucocytes; moreover, by treatment of rats with (45mg/kg b.w. STZ) and whole body gamma irradiation (4Gy) showedmultiple focal hepatic necrosis associated with leucocytic cells infiltration as well as apoptosis of hepatocytes.