Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats

Memory impairment induced by intracerebroventricular (ICV) injection of streptozotocin (STZ) in rats is associated with impaired brain glucose and energy metabolism, oxidative stress and impaired cholinergic neurotransmission. Treatment with antioxidants and cholinergic agonists has been reported to produce beneficial effect in this model. However, no reports are available on drugs that improve glucose utilization and metabolism. In the present study, we evaluated the effects of pioglitazone on cognitive performance, oxidative stress and glucose utilization in ICV STZ injected rats (3 mg/kg, on day 1 and 3). Pioglitazone (10 and 30 mg/kg) was administered per oral (p.o.) for 14 days, starting 5 days prior to STZ injection. Cognitive performance was assessed using step-through passive avoidance and Morris water maze task. Malondialdehyde (MDA) and glutathione levels in brain were estimated as parameters of oxidative stress. Glucose utilization by brain was assessed as the amount of glucose consumed from the media by the brain. ICV STZ injected rats showed a severe deficit in learning and memory associated with increased MDA levels (+67.5%), decreased glutathione levels (-29.2%) and impaired cerebral glucose utilization (-44.4%). In contrast pioglitazone treatment improved cognitive performance, lowered oxidative stress and improved cerebral glucose utilization in ICV STZ rats. The present study demonstrates the beneficial effects of pioglitazone in the ICV STZ induced cognitive deficits, which can be exploited for the dementia associated with diabetes and age-related neurodegenerative disorder, where oxidative stress and impaired glucose and energy metabolism are involved.     

Intracerebroventricular injection of streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment

Recent reports suggest the involvement of free radicals in the pathophysiology of Alzheimer's disease [AD]. Streptozotocin [STZ] injection in the brain is known to cause cognitive impairment in rats and is likened to sporadic AD in humans. Though STZ is known to cause impairment in glucose and energy metabolism, it is not known whether this is associated with free radical generation. The present study was designed to investigate if the changes in learning and memory by intracerebroventricular administration of STZ are associated with changes in the markers of oxidative stress. Adult male Wistar rats [330-340 g] were injected with intracerebroventricular STZ [3 mg/kg] bilaterally stereotaxically under ketamine anesthesia [70 mg/kg]. The rats were treated with STZ twice, on day 1 and on day 3. The learning and memory behavior was analyzed using passive avoidance paradigms, elevated plus maze and the closed field activity test while the parameters of oxidative stress assessed were malondialdehyde [MDA] and glutathione. The behavioral tests were performed on day 17, 18 and 19. The rats developed significant deficits in learning, memory and cognitive behavior, indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to sham rats. On day 21, the rats were sacrificed under ether anesthesia and the brains were analyzed for biochemical studies. There was a development of oxidative stress in the brain as indicated by significant elevations in malondialdehyde [MDA] levels and decreased levels of glutathione. The study demonstrates that intracerebroventricular STZ may be appropriate model for investigations of antioxidants as potential treatment in Alzheimer's dementia.     

Protective effect of resveratrol against oxidative stress in middle cerebral artery occlusion model of stroke in rats

Free radicals have been implicated in neuronal injury during ischemia reperfusion in stroke. Trans resveratrol, a potent antioxidant, polyphenolic compound found in grapes and wines has recently been shown to have neuroprotective activity against oxidative stress in in vitro studies. In the present study the effect of chronic treatment of trans resveratrol was evaluated in focal ischemia induced by middle cerebral artery [MCA] occlusion in rats. Male Wistar rats were pretreated with trans resveratrol 20 mg/kg i.p. for 21 days and were subjected to focal ischemia by occlusion of MCA using intraluminal thread. After two hours of MCA occlusion reperfusion was allowed by retracting the thread. Animals were assessed for motor performance after 24 hours and subsequently rats were sacrificed for estimation of markers of oxidative stress [malondialdehyde [MDA] and reduced glutathione] and for evaluation of volume of infarction. Control group received vehicle and similar protocol was followed. Significant motor impairment, with elevated levels of MDA and reduced glutathione was observed in the vehicle treated MCA occluded rats. Treatment with trans resveratrol prevented motor impairment, rise in levels of MDA and reduced glutathione and also significantly decreased the volume of infarct as compared to control. The study provides first evidence of effectiveness of trans resveratrol in focal ischemia most probably by virtue of its antioxidant property.     

Effect of donepezil and lercanidipine on memory impairment induced by intracerebroventricular streptozotocin in rats

Intracerebroventricular (ICV) injection of streptozotocin (STZ) causes cognitive impairment in rats. ICV STZ is known to impair cholinergic neurotransmission by decreasing choline acetyltransferase (ChAT) levels, glucose and energy metabolism in brain and synthesis of acetyl CoA. However, no reports are available regarding the cholinesterase inhibitors in this model. In aging brain, reduced energy metabolism increases glutamate release, which is blocked by L-type calcium channel blockers. These calcium channel blockers have shown beneficial effects on learning and memory in various models of cognitive impairment. The present study was designed to investigate the influence of chronic administration of donepezil (cholinesterase inhibitor, 1 and 3 mg/kg) and lercanidipine (L-type calcium channel blocker, 0.3 and 1 mg/kg) on cognitive impairment in male Sprague-Dawley rats injected twice with ICV STZ (3 mg/kg) bilaterally on days 1 and 3. ICV STZ injected rats developed a severe deficit in learning and memory indicated by deficits in passive avoidance paradigm and elevated plus maze as compared to control rats. Cholinesterase activity in brain was significantly increased in ICV STZ injected rats. Donepezil dose-dependently inhibited cholinesterase activity and improved performance in memory tests at both the doses. Lercanidipine (0.3 mg/kg) showed significant improvement in memory. When administered together, the effect of combination of these two drugs on memory and cholinesterase activity was higher than that obtained with either of the drugs when used alone.     

Pomegranate (Punica granatum L.) flower improves learning and memory performances impaired by diabetes mellitus in rats

Oxidative stress induced by diabetes mellitus leads to damages in the brain, as a consequence of which cognitive functions is impaired. Therefore, for the treatment of diabetes mellitus, in addition to antidiabetics, antioxidants are used to cope with oxidative stress. The antioxidant ability of pomegranate flowers (PGF) to cope with the oxidative stress was investigated. Rats were divided into five groups with 12 animals in each group as given below: control, diabetes (STZ), STZ + the PGF I (300 mg/kg/day), STZ + PGF II (400 mg/kg/day) and STZ + PGF III (500 mg/kg/day).The findings from Morris water maze and probe tests showed that the animals in STZ group had impairments in learning and memory performances compared to the control group. Supplementation of PGF led to improvements in learning and memory performances of diabetic rats.While lipid peroxidation (LPO) was increased (P<0.001), glutathione (GSH) content was decreased (P<0.001) in hippocampal tissue of STZ-induced diabetic rats when compared with control values. Supplementation of PGF restored the levels of LPO and GSH towards their control values. Daily PGF supplementation to diabetic rats reduced the increase in glial-fibrilar acidic protein (GFAP) contents induced by diabetes in the hippocampus, which was significant in STZ + PGF III in comparison to STZ group (p<0.05).In conclusion, these observations suggest that PGF supplementation decreases oxidative stress and ameliorates impairment in learning and memory performances in diabetic rats. Therefore, we suggest that PGF supplementation may be clinically useful in treating neuronal deficit in diabetic patients.     

Resveratrol, a red wine polyphenol, attenuates ethanol-induced oxidative stress in rat liver

The involvement of oxidative stress in the pathogenesis of alcoholic diseases in the liver has been repeatedly confirmed. Resveratrol, a natural phytoalexin present in grape skin and red wine possesses a variety of biological activities including antioxidant. This study was conducted to evaluate whether resveratrol has a preventive effect on the main indicators of hepatic oxidative status as an expression of the cellular damage caused by free radicals, and on antioxidant defence mechanism during chronic ethanol treatment. Wistar rats were treated daily with 35% ethanol solution (3 g/kg/day i.p.) during 6 weeks and fed basal diet or basal diet containing 5 g/kg resveratrol. Control rats were treated with i.p. saline and fed basal diet. Experimentally, chronic ethanol administration leads to hepatotoxicity as monitored by the increase in the level of hepatic marker enzymes and the appearance of fatty change, necrosis, fibrosis and inflammation in liver sections. Ethanol also enhanced the formation of MDA in the liver indicating an increase in lipid peroxidation, a major end-point of oxidative damage, and caused drastic alterations in antioxidant defence systems. Particularly the activities of hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were found reduced by ethanol treatment while glutathione reductase (GR) activity was unchanged. Dietary supplementation with resveratrol during ethanol treatment inhibited hepatic lipid peroxidation and ameliorated SOD, GPx and CAT activities in the liver. Conclusively, we can suggest that resveratrol could have a beneficial effect in inhibiting the oxidative damage induced by chronic ethanol administration, which was proved by the experiments that we conducted on rats.     

Neuroprotective Effects of Bacopa monnieri in Experimental Model of Dementia

Alzheimer disease (AD) is characterized by dementia that begins as mild short term memory deficit and culminates in total loss of cognitive and executive functions. The present study was conducted to evaluate the neuroprotective potential of Bacopa monnieri (BM), an Indian traditional medicinal plant effective against cognitive impairment, in colchicine-induced dementia. Intracerebroventricular administration of colchicine (15?μg/5?μl) induced cognitive impairment in rats as assessed by elevated plus maze. This was accompanied by a significant increase in oxidative stress in term of enhanced levels of lipid peroxidation and protein carbonyls. Concomitantly, decrease in activity of antioxidant enzymes was observed in colchicine treated animals. BM (50?mg/kg body weight) supplementation reversed memory impairment observed in the colchicine treated rats. BM administration attenuated oxidative damage, as evident by decreased LPO and protein carbonyl levels and restoration in activities of the antioxidant enzymes. The activity of membrane bound enzymes (Na(+)K(+) ATPase and AChE) was altered in colchicine treated brain regions and BM supplementation was able to restore the activity of enzymes to comparable values observed in controls. The results suggest therapeutic potential of BM in the treatment of AD associated cognitive decline.     

Effects of acupuncture on declined cerebral blood flow,impaired mitochondrial respiratory function and oxidative stress in multi-infarct dementia rats

Brain energy disorders and oxidative stress due to chronic hypoperfusion were considered to be the major risk factors in the pathogenesis of dementia. In previous studies, we have demonstrated that acupuncture treatment improved cognitive function of VaD patients and multi-infarct dementia (MID) rats. Acupuncture therapy also increased the activities of glycometabolic enzymes in the brain. But it is not clear whether acupuncture treatment compensates neuronal energy deficit after cerebral ischemic through enhancing the activities of glucose metabolic enzymes and preserving mitochondrial function, and whether acupuncture neuroprotective effect is associated with activations of mitochondrial antioxidative defense system. So, the effect of acupuncture therapy on cognitive function, cerebral blood flow (CBF), mitochondrial respiratory function and oxidative stress in the brain of MID rats was investigated in this study. The results showed that acupuncture treatment significantly improved cognitive abilities and increased regional CBF of MID rats. Acupuncture elevated the activities of total SOD, CuZnSOD and MnSOD, decreased the level of malondialdehyde (MDA) and superoxide anion, regulated the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG) in mitochondria, and raised the level of the respiratory control index (RCI) and P/O ratio and the activities of mitochondrial respiratory enzymes of MID rats. These results indicated that acupuncture treatment improved cognitive function of MID rats; and this improvement might be due to increased CBF, which ameliorated mitochondrial dysfunction induced by ischemia and endogenous oxidative stress system of brain.     

Protective effect of curcumin against intracerebral streptozotocin induced impairment in memory and cerebral blood flow

AimsThe aim of the present study is to investigate the effect of curcumin on cerebral blood flow (CBF), memory impairment, oxidative stress and cholinergic dysfunction in intracerebral (IC) streptozotocin (STZ) induced memory impairment in mice.Main methodsMemory impairment was induced by STZ (0.5 mg/kg, IC) administered twice with an interval of 48 h in mice. Memory function was assessed by Morris water maze and passive avoidance test. CBF was measured by Laser Doppler Flowmetry (LDF). To study the preventive effect, curcumin (10, 20 and 50 mg/kg, PO) was administered for 21 days starting from the first dose of STZ. In another set of experiment, curcumin was administered for 7 days from 19th day after confirming STZ induced dementia to observe its therapeutic effect. Biochemical parameters of oxidative stress and cholinergic function were estimated in brain on day 21.Key findingsThe major finding of this study is that STZ (IC) caused a significant reduction in CBF along with memory impairment, cholinergic dysfunction and enhanced oxidative stress. Curcumin dose dependently improved CBF in STZ treated mice together with amelioration of memory impairment both in preventive and therapeutic manner.SignificanceThe present study clearly demonstrates the beneficial effects of curcumin, the dietary staple of India, on CBF, memory and oxidative stress which can be exploited for dementia associated with age related vascular and neurodegenerative disorders.     

Anthocyanins as a potential pharmacological agent to manage memory deficit,oxidative stress and alterations in ion pump activity induced by experimental sporadic dementia of Alzheimer's type

Anthocyanins (ANT) are polyphenolic flavonoids with antioxidant and neuroprotective properties. This study evaluated the effect of ANT treatment on cognitive performance and neurochemical parameters in an experimental model of sporadic dementia of Alzheimer's type (SDAT). Adult male rats were divided into four groups: control (1 ml/kg saline, once daily, by gavage), ANT (200 mg/kg, once daily, by gavage), streptozotocin (STZ, 3 mg/kg) and STZ plus ANT. STZ was administered via bilateral intracerebroventricular (ICV) injection (5 μl). ANT were administered after ICV injection for 25 days. Cognitive deficits (short-term memory and spatial memory), oxidative stress parameters, and acetylcholinesterase (AChE) and Na⁺-K⁺-ATPase activity in the cerebral cortex and hippocampus were evaluated. ANT treatment protected against the worsening of memory in STZ-induced SDAT. STZ promoted an increase in AChE and Na⁺-K⁺-ATPase total and isoform activity in both structures; ANT restored this change. STZ administration induced an increase in lipid peroxidation and decrease in the level of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), in the cerebral cortex; ANT significantly attenuated these effects. In the hippocampus, an increase in reactive oxygen species (ROS), nitrite and lipid peroxidation levels, and SOD activity and a decrease in CAT and GPx activity were seen after STZ injection. ANT protected against the changes in ROS and antioxidant enzyme levels. In conclusion, the present study showed that treatment with ANT attenuated memory deficits, protected against oxidative damage in the brain, and restored AChE and ion pump activity in an STZ-induced SDAT in rats.     

Effect of glycolysis inhibition on mitochondrial function in rat brain

Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.     

Protective effect of daidzein against streptozotocin‐induced Alzheimer's disease via improving cognitive dysfunction and oxidative stress in rat model

Oxidative stress is performing an essential role in developing Alzheimer's disease (AD), and age‐related disorder and other neurodegenerative diseases. In existing research, we have aimed at investigating the daidzein (4′,7‐dihydroxyisoflavone) effect (10 and 20 mg/kg of body weight), as a free radical scavenger and antioxidant in streptozotocin (STZ) infused AD in rat model. Daidzein treatment led to significant improvement in intracerebroventricular‐streptozotocin (ICV‐STZ)‐induced memory and learning impairments that was evaluated by Morris water maze test and spontaneous locomotor activity. It significantly restored the alterations in malondialdehyde, catalase, superoxide dismutase, and reduced glutathione levels. In addition, histopathological observations in cerebral cortex and hippocampal areas confirmed the neuroprotective effect of daidzein. These outcomes provide experimental proof showing preventive effect of daidzein on memory, learning dysfunction and oxidative stress in case of ICV‐STZ rats. In conclusion, daidzein offers a potential treatment module for various neurodegenerative disorders with regard to mental deficits like AD.     

Red wine prevents brain oxidative stress and nephropathy in streptozotocin-induced diabetic rats

We have studied the effects of red wine on brain oxidative stress and nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced in Wistar rats with a single intraperitonally injection of STZ (50 mg/kg). Two weeks before and four weeks after injection, red wine was given orally in both normal and diabetic rats. Blood samples were taken from the neck vascular trunk in order to determine the glucose, triglycerides, total cholesterol, HDL-cholesterol (HDL-c), atherogenic index (AI), total protein, blood urea nitrogen (BUN), creatinine, insulin, lipid peroxidation products, reduced glutathione (GSH) and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. As well, we estimated the lipid peroxidtion, GSH and SOD, GSH-Px and catalase activities in brain and renal homogenates, and the excretion of albumin, proteins and glucose in urine over 24 h period. The administration of STZ caused significant increases in levels of glycosuria, proteinuria, albuminuria, glycemia, total cholesterol and AI, as well as in lipid peroxidation products in the brain, plasma and kidney, whereas it decreased the GSH content and SOD, GSH-Px and catalase activities. Treatment with red wine significantly prevented the changes induced by STZ. These data suggested that red wine has a protective effect against brain oxidative stress, diabetic nephropathy and diabetes induced by STZ, as well as it protects against hypercholesterolemia and atherogenic risk.     

Resveratrol abrogates alcohol-induced cognitive deficits by attenuating oxidative–nitrosative stress and inflammatory cascade in the adult rat brain

Chronic alcohol intake is known to induce permanent cognitive deficits along with enhanced oxidative–nitrosative stress and activation of neuroinflammatory cascade. In the present study, we investigated the protective effect of resveratrol, a natural polyphenolic phytoalexin against chronic alcohol-induced cognitive dysfunction and neuroiflammatory cascade in the brain of adult rats chronically administered ethanol. Male Wistar rats were adminstered ethanol (10 g/kg; oral gavage) for ten weeks and treated with resveratrol (5, 10 and 20 mg/kg) for the same duration. Ethanol-exposed rats showed impaired spatial navigation in the Morris water maze test and poor retention in the elevated plus maze task which was coupled with enhanced acetylcholinesterase activity, increased oxidative–nitrosative stress, cytokines (TNF-alpha and IL-1beta), NF-kappa β and caspase-3 levels in different brain regions (cerebral cortex and hippocampus) of ethanol-treated rats. Co-administration with resveratrol significantly and dose-dependently prevented all the behavioral, biochemical and molecular deficits. Correlatively, the results of the present study revealed that treatment with resveratrol significantly prevented cognitive deficits induced by chronic ethanol exposure not only by modulating oxido–nitrosative stress but also by attenuating the enhanced levels of pro-inflammatory cytokines (TNF-α and IL-1β), NF-kβ and caspase-3 in different brain regions of ethanol treated rats. Therefore, mechanism underlying the neuroprotective effects of resveratrol observed in our study may be due to its antioxidant, anti-inflammatory and neuromodulating activities.     

Selenium-Vitamin E Combination Modulates Endometrial Lipid Peroxidation and Antioxidant Enzymes in Streptozotocin-Induced Diabetic Rat

Diabetes mellitus is associated with diabetic impairment of uterine function, ultimately leading to reduced fertility. Its etiology may involve oxidative damage by reactive oxygen substances, and protection against this damage can be offered by antioxidant supplementation. In the present study, the effects of a vitamin E-plus-selenium (VESe) combination on lipid peroxidation (MDA) and the scavenging enzyme activity in the uterine endometrium of streptozotocin (STZ)-induced diabetic rats were investigated. Twenty-four female rats were equally divided into three groups as follows: group I (control); group II (diabetic); group III (diabetic + VESe), STZ + vitamin E (60?mg/kg over 1?day) + selenium-treated (Na2SeO3, 1?mg/kg over 1?day). After 4?weeks of receiving the VESe treatment, endometrium samples were taken from the uterus. Although the VESe treatment decreased the MDA and blood glucose levels in the STZ group, the observed values remained significantly higher than in the controls. Catalase, superoxide dismutase, and glutathione peroxidase activities and body weight gain were significantly (p?<?0.01) lower in STZ groups as compared to control group, whereas their activities were (p?<?0.01) increased by VESe treatment. However, there was no significant difference on body weight gain and uterine weights between control and STZ + VESe groups. In conclusion, the endometrial complications caused by oxidative stress, and the abnormal blood glucose levels in diabetic of rats, can be alleviated by strengthening the physiological antioxidative defense through the administration of vitamin E and Se.     

Curcuminoids modulates oxidative damage and mitochondrial dysfunction in diabetic rat brain

Diabetes exacerbates neuronal injury induced by hyperglycemia mediated oxidative damage and mitochondrial dysfunction. The aim of the present study is to investigate the effects of curcuminoids, polyphenols of Curcuma longa (L.) on oxidative stress and mitochondrial impairment in the brain of streptozotocin (STZ)-induced diabetic rats. A marked increase in lipid peroxidation and nitrite levels with simultaneous decrease in endogenous antioxidant marker enzymes was observed in the diabetic rat brain, which was restored to normal levels on curcuminoids treatment. Down-regulation of mitochondrial complex I and IV activity caused by STZ induction was also up-regulated on oral administration of curcuminoids. Moreover, curcuminoids administration profoundly elevated the ATP level, which was earlier reduced in the diabetic brain. These results suggest that curcuminoids exhibit a protective effect by accelerating antioxidant defense mechanisms and attenuating mitochondrial dysfunction in the brain of diabetic rats. Curcuminoids thus may be used as a promising therapeutic agent in preventing and/or delaying the progression of diabetic complications in the brain.     

Effects of melatonin on oxidative-antioxidative status of tissues in streptozotocin-induced diabetic rats

In view of the antioxidant properties of melatonin, the effects of melatonin on the oxidative-antioxidative status of tissues affected by diabetes, e.g. liver, heart and kidneys, were investigated in streptozotocin (STZ)-induced diabetic rats in the present study. Concentrations of malondialdehyde (MDA) and reduced glutathione (GSH), and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in the tissues were compared in three groups of 10 rats each (control non-diabetic rats (group I), untreated diabetic rats (group II) and diabetic rats treated with melatonin (group III)). In the study groups, diabetes developed 3 days after intraperitoneal (i.p.) administration of a single 60 mg kg(-1) dose of STZ. Thereafter, while the rats in group II received no treatment, the rats in group III began to receive a 10 mg kg(-1) i.p. dose of melatonin per day. After 6 weeks, the rats in groups II and III had significantly lower body weights and higher blood glucose levels than the rats in group I (p < 0.001 and p < 0.001, respectively). MDA levels in the liver, kidney and heart of group II rats were higher than that of the control group (p < 0.01, p < 0.05, p < 0.01, respectively) and diabetic rats treated with melatonin (p < 0.05). The GSH, GSH-Px and SOD levels increased in diabetic rats. Treatment with melatonin changed them to near control values. Our results confirm that diabetes increases oxidative stress in many organs such as liver, kidney and heart and indicate the role of melatonin in combating the oxidative stress via its free radical-scavenging and antioxidant properties.     

Resveratrol, a polyphenolic phytoalexin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats

The effects of resveratrol, a polyphenolic phytoalexin present in red wine have been investigated on hyperalgesia and cold allodynia in streptozotocin (STZ) induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65mg/kg). After 4-weeks of STZ injection, diabetic rats exhibited a significant thermal hyperalgesia and cold allodynia along with increased plasma glucose and decreased body weights as compared with controls rats. Chronic treatment with resveratrol (10mg/kg orally) from week 4 to week 6 significantly attenuated the cold allodynia and thermal hyperalgesia. The results emphasize the role of oxidative stress in development of hyperalgesia and cold allodynia in diabetic animals and point towards the potential of resveratrol as an adjuvant therapy for the prevention and treatment of diabetic neuropathy.     

Chronic resveratrol treatment restores vascular responsiveness of cerebral arterioles in type 1 diabetic rats

Decreased dilation of cerebral arterioles via an increase in oxidative stress may be a contributing factor in the pathogenesis of diabetes-induced complications leading to cognitive dysfunction and/or stroke. Our goal was to determine whether resveratrol, a polyphenolic compound present in red wine, has a protective effect on cerebral arterioles during type 1 diabetes (T1D). We measured the responses of cerebral arterioles in untreated and resveratrol-treated (10 mg·kg(-1)·day(-1)) nondiabetic and diabetic rats to endothelial (eNOS) and neuronal (nNOS) nitric oxide synthase (NOS)-dependent agonists and to a NOS-independent agonist. In addition, we harvested brain tissue from nondiabetic and diabetic rats to measure levels of superoxide under basal conditions. Furthermore, we used Western blot analysis to determine the protein expression of eNOS, nNOS, SOD-1, and SOD-2 in cerebral arterioles and/or brain tissue from untreated and resveratrol-treated nondiabetic and diabetic rats. We found that T1D impaired eNOS- and nNOS-dependent reactivity of cerebral arterioles but did not alter NOS-independent vasodilation. While resveratrol did not alter responses in nondiabetic rats, resveratrol prevented T1D-induced impairment in eNOS- and nNOS-dependent vasodilation. In addition, superoxide levels were higher in brain tissue from diabetic rats and resveratrol reversed this increase. Furthermore, eNOS and nNOS protein were increased in diabetic rats and resveratrol produced a further increased eNOS and nNOS proteins. SOD-1 and SOD-2 proteins were not altered by T1D, but resveratrol treatment produced a decrease in SOD-2 protein. Our findings suggest that resveratrol restores vascular function and oxidative stress in T1D. We suggest that our findings may implicate an important therapeutic potential for resveratrol in treating T1D-induced cerebrovascular dysfunction.     

Chronically and acutely exercised rats: biomarkers of oxidative stress and endogenous antioxidants.

The responses to oxidative stress induced by chronic exercise (8-wk treadmill running) or acute exercise (treadmill running to exhaustion) were investigated in the brain, liver, heart, kidney, and muscles of rats. Various biomarkers of oxidative stress were measured, namely, lipid peroxidation [malondialdehyde (MDA)], protein oxidation (protein carbonyl levels and glutamine synthetase activity), oxidative DNA damage (8-hydroxy-2'-deoxyguanosine), and endogenous antioxidants (ascorbic acid, alpha-tocopherol, glutathione, ubiquinone, ubiquinol, and cysteine). The predominant changes are in MDA, ascorbic acid, glutathione, cysteine, and cystine. The mitochondrial fraction of brain and liver showed oxidative changes as assayed by MDA similar to those of the tissue homogenate. Our results show that the responses of the brain to oxidative stress by acute or chronic exercise are quite different from those in the liver, heart, fast muscle, and slow muscle; oxidative stress by acute or chronic exercise elicits different responses depending on the organ tissue type and its endogenous antioxidant levels.