ABSTRACT
BACKGROUND: Diabetic oxidative stress coexists with a reduction in the antioxidant status, which can further increase the deleterious effects of free radicals. Zinc is an essential trace element with significant antidiabetic activity. However, the acceptance of zinc compounds as promising therapeutic antidiabetic agents has been slowed due to concerns regarding chronic toxicity. Recently, we have designed, synthesized and characterized a novel zinc-flavonol complex and evaluated its antidiabetic efficacy in streptozotocin (STZ)-diabetic rats. The aim of the present study was to evaluate the role of the zinc-flavonol complex in the antioxidant status of diabetic rats. METHODS: Diabetes was induced in rats by i.p. injection of STZ. Diabetic rats were then treated with the zinc-flavonol complex (5 mg/kg, p.o.) for 30 days. The extent of oxidative stress was assessed by determining lipid peroxide levels, pancreatic tissue antioxidant enzyme activities and plasma concentrations of non-enzymatic antioxidants. In addition, nuclear levels of nuclear factor (NF)-κB p65, pancreatic nitric oxide (NO), and plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6 were determined. Pancreatic tissues were examined histologically. RESULTS: Oral treatment with the zinc-flavonol complex significantly improved antioxidant levels and alleviated levels of oxidative stress markers. Furthermore, significant increases were seen in NF-κB p65, NO, TNF-α, IL-1ß and IL-6 levels. Histological observations revealed that the zinc-flavonol complex effectively protects pancreatic ß-cells against oxidative damage. CONCLUSION: The results of the present study indicate that the zinc-flavonol complex has an antioxidative and anti-inflammatory role in the diabetic milieu.
Subject(s)
Antioxidants/pharmacology , Coordination Complexes/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Flavonols/pharmacology , Hypoglycemic Agents/pharmacology , Zinc , Animals , Antioxidants/therapeutic use , Coordination Complexes/therapeutic use , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Flavonols/therapeutic use , Hypoglycemic Agents/therapeutic use , Male , Oxidative Stress , Rats , Rats, Wistar , StreptozocinABSTRACT
Zinc is essential in the physiology of insulin and has prominent roles in the structural and functional aspects of insulin. Most of the zinc complexes so far tested for their antidiabetic potential exerts significant toxicity. Hence, the development of zinc complexes with various ligands in order to reduce the toxicity of zinc continues. In the present study, an attempt has been made to synthesize zinc-3-hydroxy flavone (Zn-flavonol) complex and it was subjected to spectral characterization. The UV-visible, IR, fluorescence, mass and NMR spectral studies provide information that complexation involves the binding of zinc ion with α hydroxyl keto group of the 3-hydroxy flavone (flavonol). Acute toxicity and dosage fixation studies revealed that the Zn-flavonol complex is non toxic and oral administration of the complex at a concentration of 5mg/kg b.w./rat/day for 30days to streptozotocin induced diabetic rats showed significant reduction in blood glucose, glycosylated hemoglobin (HbA1c), urea, uric acid and creatinine with concomitant improvement in plasma insulin and C-peptide levels. Further, the oral glucose tolerance test performed in experimental rats indicated that the Zn-flavonol complex has significant antihyperglycemic activity in streptozotocin induced diabetic rats. Also, the reduced activities of serum AST, ALT and ALP in the diabetic rats treated with the complex revealed the non-toxic nature of the zinc-flavonol complex. The antidiabetic activity of the complex was comparable with gliclazide, a standard antidiabetic drug.
