Antihyperlipidemic effect of bis-1,7-(2-hydroxyphenyl)-hepta-1,6-diene-3,5-dione, a curcumin analog, on nicotine and streptozotocin treated rats

Diabetes and smoking have been considered as major health problems individually and their seriousness related to health hazard has been well reported. Data regarding the possible contribution of cigarette smoking to the development of diabetes are scarce and inconclusive. The aim was to investigate the effect of nicotine on diabetes and to analyze the effect of bis demethoxy curcumin analog (BDMCA) in streptozotocin (STZ) and nicotine-induced toxicity. The tissue lipids were extracted according to the method of Folch et al. Plasma and tissue cholesterol was estimated by the method of Allain et al. using reagent kit. Triglycerides were estimated by the method of Foster and Dunn. Free fatty acids were estimated by the method of Falholt et al. Tissue phospholipids were estimated by the method of Zilversmit and Davis. From our study, we found that nicotine not only aggravates diabetic complications but also increased the risk for diabetes. BDMCA, at a dose 80 mg/kg body weight was found to be effective in decreasing toxic effects induced by nicotine and STZ. Our data provide new evidence that cigarette smoking is an additional important factor that could be targeted for the prevention of diabetic complications.     

Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats

We have recently shown free radical generation is associated with cognitive impairment in intracerebroventricular (ICV) streptozotocin (STZ) model of sporadic dementia of Alzheimer's type in rats. Trans resveratrol is a polyphenolic compound and is known to have antioxidant activity. In the present study, the effect of trans resveratrol was investigated on ICV STZ induced cognitive impairment and oxidative stress in rats. Adult male Wistar rats were injected with ICV STZ bilaterally, on day 1 and day 3. The learning and memory behavior was assessed 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 rats were treated with trans resveratrol chronically at doses of 10 and 20 mg/kg,i.p. for 21 days starting from day 1 of STZ injection. Trans resveratrol treatment significantly prevented ICV STZ induced cognitive impairment. There was a rise in brain glutathione and an insignificant increase in brain MDA in trans resveratrol treated ICV STZ rats as compared to significantly elevated brain MDA levels in the vehicle treated ICV STZ animals. The study demonstrates the effectiveness of trans resveratrol in preventing the cognitive deficits as well as the oxidative stress caused by ICV STZ in rats and it's potential in the treatment of neurodegenerative diseases such as Alzheimer's disease.     

Ethyl acetate fraction of Cissus quadrangularis stem ameliorates hyperglycaemia-mediated oxidative stress and suppresses inflammatory response in nicotinamide/streptozotocin induced type 2 diabetic rats

BackgroundCissus quadrangularis is a plant with great medicinal value and different parts of the plant is traditionally used for the treatment of skin infections, constipation, piles, anaemia, asthma, irregular menstruation, burns and wounds. The stems and leaves of Cissus quadrangularis has been traditionally consumed as a vegetable.ObjectiveThe current study was hypothesized to investigate the beneficial effects of ethyl acetate fraction of Cissus quadrangularis stem (CQSF) on hyperglycaemia-mediated oxidative stress and inflammatory responses in nicotinamide/streptozotocin induced diabetes mellitus.Materials and methodsExperimental diabetes was induced by intraperitoneal injection of 110 mg/kg body weight nicotinamide 15 min prior to the injection of 45 mg/kg body weight streptozotocin. Diabetic rats were administered with a daily oral dose of 100 mg/kg CQSF for 60 days after diabetes induction.ResultsDiabetic control rats showed significant (p < 0.05) increase in blood glucose, HbA1c, liver toxicity markers, inflammatory markers and lipid peroxidation products and reduction in the activities of antioxidant enzymes. The mRNA expressions of TNF-α, IL-6 and NF-κB in adipose tissue were significantly (p < 0.05) increased in diabetic group. Nuclear translocation of NF-κB p65 subunit level was greater in diabetic rats. CQSF administration significantly reversed these alterations. Histopathological alterations of liver and pancreas were also restored by CQSF treatment. The results were compared with the standard oral hypoglycaemic drug metformin. In addition, the ESI-MS and GC-MS analysis of CQSF confirmed the presence of quercetin and phenol, 2,4-bis(1,1-dimethylethyl)- respectively.ConclusionsThe present study demonstrates that CQSF exerts antidiabetic activity by potentiating the antioxidant defense system and suppressing inflammatory responses.     

Zinc supplementation ameliorates glycoprotein components and oxidative stress changes in the lung of streptozotocin diabetic rats

Zinc (Zn) is a component of numerous enzymes that function in a wide range of biological process, including growth, development, immunity and intermediary metabolism. Zn may play a role in chronic states such as cardiovascular disease and diabetes mellitus. Zn acts as cofactor and for many enzymes and proteins and has antioxidant, antiinflammatory and antiapoptotic effects. Taking into consideration that lung is a possible target organ for diabetic complications, the aim of this study was to investigate the protective role of zinc on the glycoprotein content and antioxidant enzyme activities of streptozotocin (STZ) induced diabetic rat tissues. Female Swiss albino rats were divided into four groups. Group I, control; Group II, control + zinc sulfate; Group III, STZ-diabetic; Group IV, diabetic + zinc sulfate. Diabetes was induced by intraperitoneal injection of STZ (65 mg/kg body weight). Zinc sulfate was given daily by gavage at a dose of 100 mg/kg body weight every day for 60 days to groups II and IV. At the last day of the experiment, rats were sacrificed, lung tissues were taken. Also, glycoprotein components, tissue factor (TF) activity, protein carbonyl (PC), advanced oxidative protein products (AOPP), hydroxyproline, and enzyme activities in lung tissues were determined. Glycoprotein components, TF activity, lipid peroxidation, non enzymatic glycation, PC, AOPP, hydroxyl proline, lactate dehydrogenase, catalase, superoxide dismutase, myeloperoxidase, xanthine oxidase, adenosine deaminase and prolidase significantly increased in lung tissues of diabetic rats. Also, glutathione levels, paraoxonase, arylesterase, carbonic anhydrase, and Na⁺/K⁺- ATPase activities were decreased. Administration of zinc significantly reversed these effects. Thus, the study indicates that zinc possesses a significantly beneficial effect on the glycoprotein components and oxidant/antioxidant enzyme activities.     

(E)-2-(2-(2-hydroxyphenyl)hydrazono)-1-phenylbutane-1,3-dione: Tautomery and coordination to copper(II)

(E)-2-(2-(2-hydroxyphenyl)hydrazono)-1-phenylbutane-1,3-dione (H₂L) was synthesized by azocoupling of diazonium salt of 2-hydroxyaniline with 1-phenylbutane-1,3-dione and characterized by IR, ¹H and ¹³C NMR spectroscopies and X-ray diffraction analysis. In solution, H₂L exists as a mixture of the enol-azo and hydrazone tautomeric forms and a decrease of temperature and of solvent polarity shifts the tautomeric balance to the hydrazone form. In the solid state, H₂L crystallizes from ethanol-water in the monohydrate hydrazone form, as shown by X-ray analysis. The dissociation constants of H₂L (pK₁ = 5.98 ± 0.04, pK₂ = 9.72 ± 0.03) and the stability constants of its copper(II) complex (log β₁ = 11.01 ± 0.07, log β₂ = 20.19 ± 0.08) were determined by the potentiometric method in aqueous-ethanol solution. The copper(II) complex [Cu₂(μ-L)₂]_n was isolated in the solid state and found by X-rays to be a coordination polymer of a binuclear core with a distorted square pyramidal metal coordination geometry.     

Therapeutic effect of green tea extract on oxidative stress in aorta and heart of streptozotocin diabetic rats

Hyperglycemia induced oxidative stress has been proposed as a cause of many complications of diabetes including cardiac dysfunction. The present study depicts the therapeutic effect of green tea extract on oxidative stress in aorta as well as heart of streptozotocin diabetic rats. Six weeks after diabetes induction, green tea was administered orally for 4 weeks [300 mg (kg body weight)(-1) day (-1)]. In aorta and heart of diabetic rats there was a significant increase in the activity of superoxide dismutase, catalase and glutathione peroxidase with an increase in lipid peroxides. Diabetic rats showed a significant decrease in the levels of serum and cardiac glutathione. Green tea administration to diabetic rats reduced lipid peroxides and activity of antioxidant enzymes whereas increased glutathione content. The results demonstrate that the induction of antioxidant enzymes in diabetic rats is not efficient and sufficient to reduce the oxidative stress. But green tea by providing a competent antioxidative mechanism ameliorates the oxidative stress in the aorta and heart of diabetic rats. The study suggests that green tea may provide a useful therapeutic option in the reversal of oxidative stress induced cardiac dysfunction in diabetes mellitus.     

Pain modality and spinal glia expression by streptozotocin induced diabetic peripheral neuropathy in rats

Pain symptoms are a common complication of diabetic peripheral neuropathy or an inflammatory condition. In the most experiments, only one or two evident pain modalities are observed at diabetic peripheral neuropathy according to experimental conditions. Following diabetic peripheral neuropathy or inflammation, spinal glial activation may be considered as an important mediator in the development of pain. For this reason, the present study was aimed to address the induction of pain modalities and spinal glial expression after streptozotocin injection as compared with that of zymosan inflammation in the rat. Evaluation of pain behavior by either thermal or mechanical stimuli was performed at 3 weeks or 5 hours after either intravenous streptozotocin or zymosan. Degrees of pain were divided into 4 groups: severe, moderate, mild, and non-pain induction. On the mechanical allodynia test, zymosan evoked predominantly a severe type of pain, whereas streptozotocin induced a weak degree of pain (severe+moderate: 57.1%). Although zymosan did not evoke cold allodynia, streptozotocin evoked stronger pain behavior, compared with zymosan (severe+moderate: 50.0%). On the other hand, the high incidence of thermal hyperalgesia (severe+moderate: 90.0%) and mechanical hyperalgesia (severe+moderate: 85.7%) by streptozotocin was observed, as similar to that of zymosan. In the spinal cord, the increase of microglia and astrocyte was evident by streptozotocin, only microglia was activated by zymosan. Therefore, it is recommended that the selection of mechanical and thermal hyperalgesia is suitable for the evaluation of streptozotocin induced diabetic peripheral neuropathy. Moreover, spinal glial activation may be considered an important factor.     

Effects of combined quercetin and coenzyme Q(10) treatment on oxidative stress in normal and diabetic rats

Reactive oxygen species may be actively involved in the genesis of various pathological states such as ischemia-reperfusion injury, cancer, and diabetes. Our objective was to determine if subacute treatment with combined antioxidants quercetin and coenzyme Q(10) (10 mg/kg/day ip for 14 days) affects the activities of antioxidant enzymes in normal and 30-day streptozotocin-induced diabetic Sprague-Dawley rats. Quercetin treatment raised blood glucose concentrations in normal and diabetic rats, whereas treatment with coenzyme Q(10) did not. Liver, kidney, heart, and brain tissues were excised and the activities of catalase, glutathione reductase, glutathione peroxidase, superoxide dismutase, and concentrations of oxidized and reduced glutathione were determined. In the liver of diabetic rats, superoxide dismutase, glutathione peroxidase, and levels of both oxidized and reduced glutathione were significantly decreased from the nondiabetic control, and these effects were not reversed when antioxidants were administered. In kidney, glutathione peroxidase activity was significantly elevated in the diabetic rats as compared to nondiabetic rats, and antioxidant treatment did not return the enzyme activity to nondiabetic levels. In heart, catalase activity was increased in diabetic animals and restored to normal levels after combined treatment with quercetin and coenzyme Q(10). Cardiac superoxide dismutase was lower than normal in quercetin- and quercetin + coenzyme Q(10)-treated diabetic rats. There were no adverse effects on oxidative stress markers after treatment with quercetin or coenzyme Q(10) singly or in combination. In spite of the elevation of glucose, quercetin may be effective in reversing some effects of diabetes, but the combination of quercetin + coenzyme Q(10) did not increase effectiveness in reversing effects of diabetes.     

Rooibos tea (Aspalathus linearis) partially prevents oxidative stress in streptozotocin-induced diabetic rats

The aim of this study was to investigate the effects of rooibos tea as a natural source of a wide scale of antioxidants on the prevention and treatment of oxidative stress in streptozotocin-induced diabetic rats. Expected significant changes of biochemical parameters characteristic for experimental diabetic state were found in plasma and tissues eight weeks after single dose streptozotocin application. Administration of aqueous and alkaline extracts of rooibos tea (or N-acetyl-L-cysteine for comparison) to diabetic rats did not affect markers of the diabetic status (glucose, glycated hemoglobin and fructosamine). Besides the parameters characterizing hepatotoxic effect of streptozotocin, rooibos tea significantly lowered advanced glycation end-products (AGEs) and malondialdehyde (MDA) in the plasma and in different tissues of diabetic rats, particularly MDA concentration in the lens. From these results we can conclude that antioxidant compounds in rooibos tea partially prevent oxidative stress and they are effective in both hydrophobic and hydrophilic biological systems. Therefore, rooibos tea as a commonly used beverage can be recommended as an excellent adjuvant support for the prevention and therapy of diabetic vascular complications, particularly for protecting ocular membrane systems against their peroxidation by reactive oxygen species.     

Chronic tempol treatment attenuates the renal hemodynamic effects induced by a heme oxygenase inhibitor in streptozotocin diabetic rats

Heme oxygenase-1 (HO-1) is induced by oxidative stress and plays an important role in protecting the kidney from oxidant-mediated damage in the streptozotocin (STZ) rat model of type-1 diabetes mellitus (DM-1). HO-derived metabolites, presumably carbon monoxide (CO), mediate vasodilatory influences in the renal circulation, particularly in conditions linked to elevated HO-1 protein expression or diminished nitric oxide (NO) levels. We tested the hypothesis that diabetes increases oxidative stress and induces HO-1 protein expression, which contributes to regulate renal hemodynamics in conditions of low NO bioavailability. Two weeks after the induction of diabetes with STZ (65 mg/kg iv), Sprague-Dawley rats exhibited higher renal HO-1 protein expression, hyperglycemia, and elevated renal nitrotyrosine levels than control normoglycemic animals. In anesthetized diabetic rats, renal vascular resistance (RVR) was increased, and in vivo cortical NO levels were reduced (P < 0.05) compared with control animals. Acute administration of the HO inhibitor Stannous mesoporphyrin (SnMP; 40 μmol/kg iv) did not alter renal hemodynamics in control rats, but greatly decreased glomerular filtration rate and renal blood flow, markedly increasing RVR in hyperglycemic diabetic rats. Chronic oral treatment with the SOD mimetic tempol prevented the elevation of nitrotyrosine, the HO-1 protein induction, and the increases in RVR induced by SnMP in the diabetic group, without altering basal NO concentrations or RVR. Increasing concentrations of a CO donor (CO-releasing molecule-A1) on pressurized renal interlobar arteries elicited a comparable relaxation in vessels taken from control or diabetic animals. These results suggest that oxidative stress-induced HO-1 exerts vasodilatory actions that partially maintain renal hemodynamics in uncontrolled DM-1.     

Effects of 2-(substituted-sulfanyl)-3,5-dihydro-imidazole-4-one and 2-(substituted-sulfanyl)-1H-imidazole-4,5-dione derivatives on serum HDL-cholesterol

A series of 2-substituted sulfanyl-3,5-dihydro-imidazole-4-ones and 2-substituted sulfanyl-1H-imidazole-4,5-diones was prepared and shown to increase high density lipoprotein cholesterol over other lipid fractions. Compound 1f showed efficacy in additional animal models. The major metabolite of 1f was isolated and its synthesis is reported. The effects of the metabolite on the lipid profile in rats were investigated.     

Atorvastatin reduces the plasma lipids and oxidative stress but did not reverse the inhibition of prostacyclin generation by aortas in streptozotocin diabetic rats

The effect of atorvastatin (Lipitor) on diabetes-induced changes in plasma lipids, oxidative stress and the ability of aortic tissues to generate prostacyclin was studied in streptozotocin diabetic rats. In diabetic rats, plasma total cholesterol, triglycerides and serum glucose significantly increased compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not affect hyperglycemia but significantly reduced plasma total cholesterol and triglycerides compared to diabetic rats. The oxidative stress markers urinary isoprostane, liver thiobarbituric acid reactive substances (TBARS) and plasma protein carbonyl content significantly increased in diabetic rats compared to nondiabetic rats. Atorvastatin admnistration to diabetic rats significantly reduced oxidative stress levels compared to diabetic rats, but urinary isoprostane and liver TBARS remained significantly higher than nondiabetic rats. Prostacyclin (PGI(2)) generation by aortic tissues significantly decreased in diabetic rats compared to nondiabetic rats. Atorvastatin administration to diabetic rats did not reverse that inhibition. These results were discussed in the light of the possible effects of hyperglycemia and statins on NAD(P)H-oxidase and cyclooxygenase-2 activities and the genetic difference between rats and other mammals regarding the level of vascular superoxide dismutase (SOD) activity.     

Melatonin relieves diabetic complications and regenerates pancreatic beta cells by the reduction in NF-kB expression in streptozotocin induced diabetic rats

Melatonin, a pleiotropic hormone, has many regulatory effects on the circadian and seasonal rhythms, sleep and body immune system. It is used in the treatment of blind circadian rhythm sleep disorders, delayed sleep phase and insomnia. It is a potent antioxidant, anti-inflammatory, free radical scavenger, helpful in fighting infectious disease and cancer treatment. Decreased level of circulating melatonin was associated with an increased blood glucose level, losing the anti-oxidant protection and anti-inflammatory responses. We aimed to evaluate the effect of melatonin administration, in streptozotocin (STZ) induced diabetic rats, on blood glucose level and pancreatic beta (β) cells. Diabetes mellitus was induced in Sprague dawley male rats by the intravenous (i.v) injection of 65 mg/kg of STZ. Diabetic rats received melatonin at a dose of 10 mg/kg daily for 8 weeks by oral routes. The results showed, after 8 weeks of melatonin administration, a reduction in: 1- fasting blood glucose (FBG) and fructosamine (FTA) levels, 2- kidney and liver function parameters, 3- levels of serum triglycerides, cholesterol and LDL-C, 4- malondialdehyde (MDA), 5- NF-κB expression in treated group, 6- pro-inflammatory cytokines (IL-1β and IL-12) and immunoglobulins (IgA, IgE and IgG). Furthermore, an elevation in insulin secretion was noticed in melatonin treated group that indicated β cells regeneration. Therefore, melatonin administration, in STZ induced diabetic rats; reduced hyperglycemia, hyperlipidemia and oxidative stress. Melatonin acted as an anti-inflammatory agent that reduced pro-inflammatory cytokines (IL-1β and IL-12) and oxidative stress biomarkers (MDA). Melatonin succeeded in protecting β cells under severe inflammatory situations, which was apparent by the regeneration of islets of Langerhans in treated diabetic rats. Moreover, these results can open a gate for diabetes management and treatment.     

Tissue specific expression and immunohistochemical localization of glutathione S-transferase in streptozotocin induced diabetic rats: modulation by Momordica charantia (karela) extract

In streptozotocin (STZ)-induced diabetes, destruction of pancreatic beta-cell causes an acute shortage of insulin. Increased oxidative stress is believed to be one of the main factors in the etiology and complications of diabetes. In this study we have reported hyperglycemia and glutathione-associated oxidative stress in rats one week after treatment with STZ. In our previous studies, we have reported oxidative stress-related changes in xenobiotic metabolism in tissues from STZ-induced chronic diabetic rats. Here, we demonstrate by immunohistochemistry, that glutathione S-transferase (GST) isoenzymes are differentially expressed in the liver, kidney and testis of diabetic rats. The distribution of GST isoenzymes was found to be tissue- and regio-specific. In addition, we have also shown that treatment with an extract of Momordica charantia (karela), an antidiabetic herb, modulates GST expression in diabetic rats and reverts them to the normal distribution as seen in the tissues of control rats. These results suggest that glutathione metabolism and GST distribution in the tissues of diabetic rats may play an important role in the etiology, pathology and prevention of diabetes.     

Inhibition of aldehyde dehydrogenase 2 by oxidative stress is associated with cardiac dysfunction in diabetic rats

Left ventricular (LV) dysfunction is a common comorbidity in diabetic patients, although the molecular mechanisms underlying this cardiomyopathic feature are not completely understood. Aldehyde dehydrogenase 2 (ALDH2) has been considered a key cardioprotective enzyme susceptible to oxidative inactivation. We hypothesized that hyperglycemia-induced oxidative stress would influence ALDH2 activity, and ALDH2 inhibition would lead to cardiac functional alterations in diabetic rats. Diabetes was induced by intraperitoneal (i.p.) injection of 60 mg/kg streptozotocin. Rats were divided randomly into four groups: control, untreated diabetic, diabetic treated with N-acetylcysteine (NAC) and diabetic treated with α-lipoic acid (α-LA). Cardiac contractile function, oxidative stress markers and reactive oxygen species (ROS) levels were assessed. ALDH2 activity and expression also were determined. The role of ALDH2 activity in change in hyperglycemia-induced mitochondrial membrane potential (Δψ) was tested in cultured neonatal cardiomyocytes. Myocardial MDA content and ROS were significantly higher in diabetic rats than in controls, whereas GSH content and Mn-SOD activity were decreased in diabetic rats. Compared with controls, diabetic rats exhibited significant reduction in LV ejection fraction and fractional shortening, accompanied by decreases in ALDH2 activity and expression. NAC and α-LA attenuated these changes. Mitochondrial Δψ was decreased greatly with hyperglycemia treatment, and high glucose combined with ALDH2 inhibition with daidzin further decreased Δψ. The ALDH2 activity can be regulated by oxidative stress in the diabetic rat heart. ALDH2 inhibition may be associated with LV reduced contractility, and mitochondrial impairment aggravated by ALDH2 inhibition might reflect an underlying mechanism which causes cardiac dysfunction in diabetic rats.     

Caffeic acid phenethyl ester (CAPE) protects brain against oxidative stress and inflammation induced by diabetes in rats

Diabetic patients reveal significant disorders, such as nephropathy, cardiomyopathy, and neuropathy. As oxidative stress and inflammation seem to be implicated in the pathogenesis of diabetic brain, we aimed to investigate the effects of caffeic acid phenethyl ester (CAPE) on oxidative stress and inflammation in diabetic rat brain. Diabetes was induced by a single dose of streptozotocin (45 mg kg⁻¹, i.p.) injection into rats. Two days after streptozotocin treatment 10 μM kg⁻¹ day⁻¹ CAPE was administrated and continued for 60 days. Here, we demonstrate that CAPE significantly decreased the levels of nitric oxide and malondialdehyde induced by diabetes, and the activities of catalase, glutathione peroxidase, and xanthine oxidase in the brain. However, glutathione levels were increased by CAPE. The mRNA expressions of tumor necrosis factor (TNF)-α and interferon (IFN)-γ, and inducible nitric oxide synthase (iNOS) were remarkably enhanced in brain by diabetes. CAPE treatments significantly suppressed these inflammatory cytokines (about 70% for TNF-α, 26% for IFN-γ) and NOS (completely). Anti-inflammatory cytokine IL-10 mRNA expression was not affected by either diabetes or CAPE treatments. In conclusion, diabetes induces oxidative stress and inflammation in the brain, and these may be contributory mechanisms involved in this disorder. CAPE treatment may reverse the diabetic-induced oxidative stress in rat brains. Moreover, CAPE reduces the mRNA expressions of TNF-α and IFN-γ in diabetic brain; suggesting CAPE suppresses inflammation as well as oxidative stress occurred in the brain of diabetic patients.     

Advanced glycation end products and antioxidant status in nondiabetic and streptozotocin induced diabetic rats: effects of copper treatment

The effects of Cu(II) supplementation on glycemic parameters, advanced glycation end products (AGEs), antioxidant status (glutathione; GSH and total antioxidant capacity; TAOC) and lipid peroxidative damage (thiobarbituric acid-reactive substances, TBARS) were investigated in streptozotocin (STZ) induced diabetic rats. The study was carried out on Wistar albino rats grouped as control (n = 10), CuCl₂ treated (n = 9), STZ (n = 10) and STZ,CuCl₂ treated (n = 9). STZ was administered intraperitoneally at a single dose of 65 mg/kg and CuCl₂, 4 mg copper/kg, subcutaneously, every 2 days for 60 days. At the end of this period, glucose(mg/dl), Cu(μg/dl), TBARS(μmol/l), TAOC(mmol/l) were measured in plasma, GSH(mg/gHb) in erythrocytes and glycated hemoglobin (GHb)(%) in blood. Plasma AGE-peptides(%) were measured by HPLC flow system with spectrofluorimetric and spectrophotometric detectors connected on-line. Data were analyzed by the non-parametric Kruskal–Wallis and Mann–Whitney U test. In the STZ group glucose, GHb and AGE-peptide levels were all significantly higher than the control group (P < 0.01, P < 0.05, and P < 0.01, respectively). CuCl₂ treated group had significantly lower glucose but significantly higher GHb, TAOC and TBARS levels than the control group (P < 0.05, P < 0.001, P < 0.05 and P < 0.001, respectively). STZ,CuCl₂ treated group had significantly higher GHb, TAOC and TBARS levels compared with the control group (P < 0.001, P < 0.05 and P < 0.05, respectively); but only TAOC level was significantly higher than the STZ group (P < 0.01). This experimental study provides evidence that copper intake increases total antioxidant capacity in both nondiabetic and diabetic states. However despite the potentiated antioxidant defence, lipid peroxidation and glycation enhancing effects of CuCl₂ are evident under nondiabetic conditions.     

Effects of melatonin on oxidative stress and spatial memory impairment induced by acute ethanol treatment in rats

Melatonin has recently been suggested as an antioxidant that may protect neurons from oxidative stress. Acute ethanol administration produces both lipid peroxidation as an indicator of oxidative stress in the brain and impairs water-maze performance in spatial learning and memory tasks. The present study investigated the effect of melatonin against ethanol-induced oxidative stress and spatial memory impairment. The Morris water maze was used to evaluate the cognitive functions of rats. Thiobarbituric acid reactive substances (TBARS), which are the indicators of lipid peroxidation, and the activities of antioxidative enzymes (glutathione peroxidase and superoxide dismutase) were measured in the rat hippocampus and prefrontal cortex which form interconnected neural circuits for spatial memory. Acute administration of ethanol significantly increased TBARS levels in the hippocampus. Combined melatonin-ethanol treatment caused a significant increase in glutathione peroxidase activities and a significant decrease of TBARS in the rat hippocampus. In the prefrontal cortex, there was only a significant decrease of TBARS levels in the combined melatonin-ethanol receiving group as compared to the ethanol-treated group. Melatonin did not affect the impairment of spatial memory due to acute ethanol exposure, but melatonin alone had a positive effect on water maze performances. Our study demonstrated that melatonin decreased ethanol-induced lipid peroxidation and increased glutathione peroxidase activity in the rat hippocampus.     

The anti-hyperglycemic activity of the fruiting body of Cordyceps in diabetic rats induced by nicotinamide and streptozotocin

Little scientific evidence exists to support the numerous herbs used to improve diabetes-related metabolic disorders. Cordyceps, a Chinese herbal medicine with fruiting body and carcass, has been proposed to have multiple medicinal activities. The objective of this study was to investigate the effects of fruiting body and carcass of Cordyceps on hyperglycemia. Male Wistar rats administered with placebo (STZ group), 1 g of fruiting body (FB group), 1 g of carcass (CC group), or 1g of fruiting body plus carcass (CF group) of Cordyceps for four weeks (d1 to d28) were injected with nicotinamide (200 mg/kg) and streptozotocin (65 mg/kg) on d15. Animals fed with placebo and injected with saline acted as the controls (CON group). The results showed that water intake (d15 to d29), changes in fasting blood glucose concentration (d15 to d26), and serum concentrations of fructosamine (d29) were significantly greater in the STZ, CC and CF groups than in the CON and FB groups (one-way ANOVA, P < 0.05). The diabetic rats had significantly lower weight gain and higher blood glucose response in oral glucose tolerance test than the control rats; and these changes were significantly reduced by administrating the fruiting body of Cordyceps. Our results revealed that fruiting body, not carcass, of Cordyceps attenuated the diabetes-induced weight loss, polydipsia and hyperglycemia, and these improvements suggest that fruiting body of Cordyceps has a potential to be the functional food for diabetes.