EFFECT OF SELECTED STRUCTURALLY-RELATED FLAVONOIDS ON KEY BIOINDICES OF NEUROLOGIC DYSFUNCTION IN FRUCTOSE/STREPTOZOTOCIN-INDUCED TYPE-2 DIABETIC RATS

Abstract

Diabetes and diabetic complications such as diabetic neurologic dysfunction are on the increase worldwide and there is need for effective therapeutic options. This study evaluated the effect of the structurally-related flavonoids, taxifolin, eriodictyol, rutin and quercetin on key bioindices of neurologic dysfunction in fructose/streptozotocin-induced type-2 diabetic rats. Male Wistar rats received 10% fructose in their drinking water for fourteen days followed by a single intraperitoneal injection of 40 mg/kg body weight streptozotocin. The resulting diabetic rats were post-treated with taxifolin (0.25, 0.5 and 1.0 mg/kg), eriodictyol (0.25, 0.5 and 1.0 mg/kg), rutin (5.0, 10 and 20 mg/kg) or quercetin (5.0, 10 and 20 mg/kg) for 14 days. After the period of treatments, biochemical estimations and histopathological evaluation were carried out on the hippocampi, striata and cortices of the animals. Results showed significant elevated blood glucose and glycated hemoglobin concentrations in the diabetic control rats (341 mg/dl and 7.30 % respectively) compared with normal control rats (211 mg/dl and 5.80 %) (p<0.0001). In the brain tissues, GSH concentrations and activities of superoxide dismutase, catalase and glutathione peroxidase were decreased while lipid peroxidation and protein carbonylation were exacerbated in the diabetic animals in comparation to the normal control rats. In addition, induction of diabetes occasioned an increase in acetycholinesterase (AChE) activity, tyrosine hydroxylase (TH) activity, and dopamine (DA) concentration, but a decrease in Na+/K+-ATPase activity. The flavonoids significantly (p<0.0001) reduced the elevated blood glucose and glycated hemoglobin concentrations in the diabetic rats. There was significant (p<0.0001) increase in activities of SOD, CAT, GPx, and GSH concentration but a decrease in lipid peroxidation, and protein carbonyl concentrations. In addition, there were decreases DA concentration, AChE v activity, TH and increase in Na+/K+-ATPase activities in rats post-treated with the selected flavonoids. An increase in complex 1 activity as reported in this work was an evidence of mitochondrial dysfunction and this was significantly (p<0.0001) decreased in the diabetic rats post-treated with the selected flavonoids. These results were consistent with the histopathological findings which showed significant attenuation of neuronal cell death in diabetic rats post-treated with the selected flavonoids. Comparatively, it can be inferred from the results that eriodictyol showed better neuroprotection than taxifolin, while quercetin had better neuroprotection than rutin. In conclusion, these data showed the antioxidants and neuroprotective effects of the selected structurally-related flavonoids against fructose/STZ-induced type-2 diabetic rats.