Effect of quercetin on brain protein kinase C-alpha expression and serotonin level in streptozotocin-induced diabetic rats

ABSTRACT

Hyperglycemia is a key factor in diabetic complications. However, the mechanism of hyperglycemia-induced brain changes remains poorly understood. The aim of the present study was to investigate the effect of diabetes on serotonin [5-hydroxytryptamine; 5-HT] levels and protein kinase C-alpha [PKC-alpha] expression in brain. The potential protective effect of quercetin [QE]; as phytochemical on diabetic brain was additionally studied. This study was carried out on 60 adult male albino rats divided into three main groups; group I [control] included 20 vehicle-treated rats, group II [diabetic] consisted of 20 rats injected once intraperitonially with streptozotocin [STZ; 50mg/kb body weight] amid group III [insulin-treated diabetic] comprised 20 diabetic rats injected subcutaneously with insulin [SIU/kg/day]. Each group was subdivided into 2 subgroups; subgroup I [non-QE treated] and subgroup 2[QE-treated]. QE was administered orally [10mg/kg/day]. At the end of the implemental period, all rats were sacrificed, blood samples were withdrawn and their brains were rapidly removed and dissected. 5-HT was extracted from brain samlples and their concentrations were estimated fluorophotometrically. PKC-alpha expression was quantitated by immunoblot from extracted brain samples. The STZ-induced diabetic rats showed significant marked hyperglycemia and higher brain PKC-alpha expression as compared to both control and insulin-treated diabetic groups. However, brain 5-HT concentrations did not differ significantly between the three studied groups. Only in diabetic rats, QE administration produced a significant increase in 5-HT concentrations and a decrease in PKC-alpha expression but with no effect on blood glucose levels. A highly significant direct correlation was found between blood glucose and PKC-alpha expression levels. However, 5-HT did not correlate with either blood glucose or PKC-alpha expression. it could be concluded that STZ-induced chronically hyperglycemic rats were associated with enhanced PKC-alpha expression as well as unaltered neurotransmitter; 5-HT in brain. QE seems to act perfectly in diabetic rats by mechanisms other than antihyperglycemic action. The neuroprotective effect of QE in diabetics was suggested to be through both elevating 5-HT and lowering PKC-alpha expression. Consequently, controlling hyperglycemia is still the most essential approach for primary prevention of diabetic complications