Neuroprotective effect of resveratrol in diabetic cerebral ischemic-reperfused rats through regulation of inflammatory and apoptotic events

Abstract

BackgroundDiabetes and cerebral ischemic-reperfusion are among the most common causes of neurological complications in Egypt. The prevalence of diabetes in Egypt is high and it can be considered as a major clinical and public health problem.MethodsBlood glucose, lipid profile, oxidative stress makers (cerebral MDA & GSH), cerebral interleukin-4 (IL-4) level and cerebral cyclooxygenase-2 (COX-2) gene expression were measured in male albino rats weighing 200 ± 20 g. The rats were divided into five groups, normal control group, diabetic group (diabetes was induced by single dose of streptozotocin [STZ]), diabetic cerebral ischemic-reperfused group, two treated groups (diabetic and diabetic ischemic-reperfused), both groups treated with resveratrol. Histological study was done using H&E, AgNOR and cresyl violet stains. Immunohistochemistry for Bax and COX-2 was done with morphometric study.ResultsDiabetic and diabetic cerebral ischemic- reperfused rats showed significant increase in serum glucose level, serum TAG, serum LDL-C, atherogenic index, cerebral MDA and upregulation of COX-2 gene expression. These groups showed significant decrease in serum HDL, cerebral IL-4 and depletion of cerebral GSH when compared to normal control rats. Treating these groups with resveratrol resulted in significant decrease in serum glucose level, serum TAG, TC, serum LDL-C, atherogenic index, cerebral MDA and downregulation of COX-2 gene expression. The results of COX-2 gene expression were confirmed by COX-2 immunohistochemistry. Also, significant increase in serum HDL, cerebral IL-4 and cerebral GSH contents could be observed in these treated groups as compared to normal control group. Cerebral apoptotic index and optical density of Bax reaction revealed significant increase in diabetic and diabetic cerebral ischemic-reperfused rats while treatment of these groups with resveratrol resulted in significant decrease in cerebral apoptotic index and optical density of Bax reaction. These apoptotic results were confirmed with AgNOR and cresyl violet stains.ConclusionThe results of this research suggest that upregulation of cerebral COX-2 gene along with the decrease in cerebral IL-4 and enhanced cerebral apoptosis is critically involved in cerebral damage associated with diabetes and cerebral ischemic-reperfusion. Resveratrol can ameliorate these effects and has promising neuroprotective effect in diabetic-induced cerebral complications.

Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats

“…This attenuation of diabetic neuropathy likely reflects the ROS scavenging capabilities of resveratrol, preventing neuronal cell death, as reported previously (48)(49)(50) .…”

Resveratrol Inhibits Periodontitis‐Related Bone Loss in Rats Subjected to Cigarette Smoke Inhalation

“…Interestingly, administration of RESV alone or in combination with curcumin enhanced levels of this cytokine 18 . The positive immunomodulatory impact of RESV by inducing increased levels of IL‐4 has also been demonstrated in other experimental model studies, in DM‐induced cerebral complications, 35 and in therapy of autoimmune encephalomyelitis 36 …”

Resveratrol neuroprotection in stroke and traumatic CNS injury

“…Resveratrol treatment was also shown to inhibit TNFα and interleukin-1β (IL-1β) in following ischemic stroke in adult mice (Shin et al, 2010). Another potent anti-inflammatory action of resveratrol is its ability to inhibit cyclooxygenase-1 and -2 (COX-1 and COX-2) leading to reduced pro-inflammatory arachadonic acid (AA) metabolism (Mohamed et al, 2014; Simao et al, 2012a). In rat microglial cultures, resveratrol treatment was shown to inhibit LPS-induced microsomal prostaglandin E synthase-1 (mPGES-1) and the concomitant formation prostaglandin E2 (PGE 2 ), and ROS-induced 8-iso-prostaglandin F 2α (8-iso-PG F 2α ) indicating its further anti-inflammatory potential (Candelario-Jalil et al, 2007).…”