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Abstract Mohamed Khairy Mohamed (2011): Biochemical studies on rosiglitazone and\or hesperidin in diabetic irradiated experimental animals. Ain Shams University, Biochemistry Department-Faculty of Science, Cairo, Egypt. The present study was designed to investigate the biochemical and histopathological effect of rosiglitazone and hesperidin in diabetic irradiated rats. In addition, anti-inflammatory (acute inflammation) and analgesic effects (centrally mediated analgesia) were also assessed. Type 2 diabetes mellitus (T2DM) was induced in rats by a single intraperitoneal (i.p) injection of streptozotocin (65 mg/kg b.wt.; STZ) followed by single i.p administration of nicotinamide (110 mg/kg b.wt.; NIC). Diabetic rats were irradiated with a single low dose γ-ray (0.5 Gy) at the beginning of study. Rosiglitazone (4 mg/kg b.wt.; p.o.) and hesperidin (100 mg/kg b.wt.; p.o.) were administered daily for 30 days after T2DM induction. At the end of experimental period, blood and tissue samples were collected and blood glucose, glycosylated hemoglobin (HbA1c), insulin, adiponectin, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, oxidative stress, creatinine kinasemonoenzyme B (CK-MB), lactate dehydrogenase (LDH),Creactive protein (CRP), nitric oxide (NO), body weight, heart weight, heart to body weight ratio, hematocrit %, hyaluronidase activity, liver function, kidney function as well as histopathological examination of heart, liver and kidney were determined. STZ injection significantly elevated (p<0.01) all biochemical parameters except plasma adiponectin, serum SOD and GSH levels were significantly reduced (p<0.01) as compared to their respective control group and produced pathological alterations in all examined tissues. Treatment of rats with rosiglitazone, hesperidin and low dose radiation significantly reduced (p<0.01) blood glucose, HbA1c, insulin, total cholesterol, triglycerides, LDL-C, VLDL-C, MDA, CK-MB, LDH, CRP, xvi AST, ALT, ALP, creatinine, urea and significantly elevated adiponectin, HDL-C, SOD, GSH and ameliorated HOMA-IR and AI as compared to diabetic control group. It was observed that rosiglitazone treatment alone showed a significant elevation (p<0.01) in serum hyaluronidase activity, CK-MB, LDH, final body weight, heart weight and heart to body weight ratio as compared to diabetic irradiated rats, diabetic irradiated rats treated with hesperidin alone and diabetic irradiated rats treated with rosiglitazone and hesperidin (combination). Moreover, diabetic irradiated rats treated with rosiglitazone alone revealed pathological alterations in heart and liver sections. However, other diabetic treated groups showed reversal of all pathological lesions. All diabetic treated groups showed a marked protection of renal tissue and reversal of all pathological changes exhibited by STZ in diabetic control kidney sections. Anti-inflammatory effect of rosiglitazone and hesperidin was verified through carrageenan induced paw edema model and their combination was the most potent. Hesperidin exerted a potent analgesic activity in hot plate test, on the contrary, rosiglitazone devoided of any analgesic effect. It could be concluded from the obtained results that hesperidin combination with rosiglitazone exhibited a potential beneficial effect in reducing side effects and maximized therapeutic efficacy of rosiglitazone. |