Effect of quercetin, caffeic acid and caffeic acid phenylethyl ester, solubilized in non-ionic surfactants, on histamine release in vivo and in vitro

A practical hindrance in using many therapeutic agents is their limited solubility in aqueous matrixes. This is usually overcome by incorporating the active compounds in a matrix, with the aid of a non-ionic surfactant. Three water-insoluble natural polyphenols with inherent biological activity, quercetin (CAS 117-39-5), caffeic acid and caffeic acid phenylethyl ester, were solubilized in water, with the aid of Tween 80 (an esterified and polyethoxylated derivative of sorbitan), Solutol HS15 (a polyethoxylated derivative of 12-hydroxy-stearic acid), Cremophor RH40 (a ricinoleic acid derivative) or Cremophor EL and the effect of the solubilized polyphenols on histamine release was studied in vitro (mast cells) and in vivo in the rat. In vivo Cremophor EL alone increased, and Tween 80 decreased histamine plasma levels. All four groups injected with solubilized quercetin exhibited a decrease in their plasma histamine levels. Caffeic acid solubilized in Cremophor RH40 decreased histamine levels, too. In vitro Tween 80 increased histamine release in a dose-dependent mode. Quercetin in vitro inhibited histamine release in all solubilizers used. It is concluded that the ability of the studied polyphenols to release histamine is not only depending on the condition of the storage vesicles in the mast cells, but also on the surfactant used to solubilize them.     

咖啡酸对慢性应激大鼠的抗抑郁作用

目的探讨咖啡酸对慢性应激大鼠的抗抑郁作用。方法采用各种慢性不可预见轻微刺激建立大鼠抑郁模型。21 d后,ig给予大鼠咖啡酸10,30和50 mg.kg-1,连续21 d。通过旷场实验检测中央格停留时间、水平活动和垂直活动情况,通过强迫游泳实验检测大鼠静止不动行为百分比(PI);检测海马超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量。结果与正常对照组相比,模型组大鼠在旷场实验中央格停留时间增长,水平活动和垂直活动减少,强迫游泳静止不动状态增加,SOD活性显著降低,MDA含量显著升高(P<0.01)。与模型组相比,咖啡酸10～50 mg.kg-1组能够显著缩短停留时间(P<0.05)、增加垂直活动(P<0.01),但对水平活动无明显影响。模型组PI为(79.69±15.84)%,咖啡酸10～50 mg.kg-1组PI显著降低,分别为(16.00±2.11)%,(10.33±2.92)%和(7.33±2.63)%。与正常对照组相比,模型组SOD酶活性显著降低,MDA含量显著增加(P<0.01),与模型组相比,咖啡酸10～50 mg.kg-1能够显著增加SOD酶活性,分别为模型组的1.50,2.46和2.59倍(r=0.915,P<0.01);MDA含量显著降低,分别为模型组的18.64%,11.37%和6.35%(P<0.01),且呈剂量依赖性(r=0.982,P<0.01)。咖啡酸与舍曲林5 mg.kg-1的作用相似。结论咖啡酸对慢性应激大鼠有一定的抗抑郁作用。     

Inhibitory mechanism against oxidative stress of caffeic acid

The purpose of this article is to summarize the reported antioxidant activities of a naturally abundant bioactive phenolic acid, caffeic acid (CA, 3,4-dihydroxycinnamic acid), so that new avenues for future research involving CA can be explored. CA is abundantly found in coffee, fruits, vegetables, oils, and tea. CA is among the most potential and abundantly found in nature, hydroxycinnamic acids with the potential of antioxidant behavior. Reactive oxygen species produced as a result of endogenous processes can lead to pathophysiological disturbances in the human body. Foods containing phenolic substances are a potential source for free radical scavenging; these chemicals are known as antioxidants. This review is focused on CA’s structure, availability, and potential as an antioxidant along with its mode of action. A brief overview of the literature published about the prooxidant potential of caffeic acid as well as the future perspectives of caffeic acid research is described. CA can be effectively employed as a natural antioxidant in various food products such as oils.     

咖啡酸对氧化应激诱导的PC12细胞5-脂氧酶激活的抑制作用

目的探讨咖啡酸是否通过抑制氧化应激诱导的5-脂氧酶(5-LOX)激活而减轻细胞损伤。方法稳定转染绿荧光蛋白(GFP)-5-LOX的PC12细胞,预先给予咖啡酸0.001~10μmol.L-1和对照药MK886,30min后观察缺氧缺糖/恢复(OGD/R)及过氧化氢(H2O2)160μmol.L-1处理后的变化。MTT法和碘化丙啶染色法分析细胞存活率和死亡率;荧光显微镜观察OGD 2 h/R2 h和H2O2处理40 min时5-LOX的核膜移位;ELISA法测定OGD 2 h/R 3 h时5-LOX代谢产物的生成;DCF法检测OGD 2 h/R 0.5 h细胞内活性氧(ROS)的产生。结果 OGD 2 h/R 24 h GFP-5-LOX转染和GFP-转染PC12细胞的存活率分别为(63.1±6.6)%和(70.7±6.9)%;H2O2处理24 h细胞存活率分别为(62.5±7.7)%和(75.7±9.5)%。在GFP-5-LOX转染的PC12细胞中,咖啡酸和对照药MK886可使OGD/R细胞存活率从(63.1±6.6)%分别增加到(87.3±2.0)%和(89.9±6.3)%,细胞坏死率从(31.4±1.5)%降低到(10.1±2.0)%和(11.7±1.3)%(P<0.01);使H2O2处理细胞存活率从(62.51±7.65)%增加到(92.59±4.02)%和(75.31±6.60)%;使OGD/R细胞CysLTs的生成从261.1±33.7降低到108.5±16.7和(90.6±19.5)ng.g-1蛋白(P<0.01)。此外,咖啡酸抑制OGD/R诱导PC12细胞的ROS产生,IC50值为8.021μmol.L-1;抑制OGD/R诱导的GFP-5-LOX转染的PC12细胞5-LOX核膜移位,IC50值为0.974μmol.L-1;抑制H2O2诱导的GFP-5-LOX转染的PC12细胞5-LOX核膜移位,IC50值为0.501μmol.L-1;MK886无上述作用。结论咖啡酸可抑制氧化应激诱导的PC12细胞5-LOX激活,对缺血损伤的PC12细胞具有保护作用。     

Protective effect of caffeic acid phenethyl ester (CAPE) on fluoride-induced oxidative stress and apoptosis in rat endometrium

High fluoride intake may affect biological systems by increasing free radicals, which may enhance lipid peroxidation levels of the tissues, thus leading to oxidative damage. Caffeic acid phenethyl ester (CAPE), a component of honeybee propolis, protects tissues from reactive oxygen species mediated oxidative stress in ischemia-reperfusion and toxic injuries. Several studies suggest that supplementation with anti-oxidant can influence fluoride induced tissue damage. The aims of this study was to investigate the possible role of malondialdehyde (MDA) levels and activity of superoxide dismutase (SOD) and catalase (CAT), in the pathogenesis of fluoride-induced endometrial damage and to demonstrate the effect of CAPE, the potent antioxidant, in decreasing the toxicity. Twenty-four adult female rats were randomly divided into three experimental groups, as follows: control group, fluoride-treated group (F), and fluoride plus CAPE-treated group (F+CAPE). Fluoride was given orally as 30mg/L NaF solution in spring water daily for 45 days. CAPE was co-administered intraperitoneally (i.p.) with a dose of 10μM/(kgday) for 46 days. Extensive formation of DNA strand breaks, the typical biochemical feature of apoptosis, was detected with the use of the terminal deoxynucleotidyl transferase (TdT)-mediated d UTP-biotin nick and labeling (TUNEL) method. The activities of antioxidant enzymes such as SOD and CAT as well as the concentration of MDA, as an indicator of lipid peroxidation, were measured to evaluate oxidative stress in homogenates of the endometrium. Fluoride administration increased MDA levels (p<0.05), decreased SOD (p<0.05) and CAT (p<0.05) activities. CAPE co-administration with fluoride treatments caused significantly decreased MDA levels (p<0.05), increased SOD (p<0.05) and CAT (p<0.05) activities in endometrial tissue when compared with F alone. Diffuse apoptosis in glandular epithelium and stromal cells was found by TUNEL method in endometrial tissues of rats treated with fluoride. The severity of these lesions was reduced by administration of CAPE. In conclusion, our study demonstrated that MDA may play an important role in the pathogenesis of fluoride-induced oxidative endometrial damage. CAPE may have protective aspects in this process by its antioxidant and anti-inflammatory effect.     

Succinic acid monoethyl ester prevents oxidative stress in streptozotocin-nicotinamide-induced type2 diabetic rats

Succinic acid mono ethyl ester (EMS) was recently proposed as an insulinotropic tool in the treatment of non-insulin dependent diabetes mellitus. The aim of this study was to investigate the effect of EMS on oxidative stress in a streptozotocin (STZ)-nicotinamide induced type 2 diabetic model. The EMS was injected intraperitoneally at 8 micro mol/g body weight for 30 days. Plasma glucose, plasma insulin, thiobarbituricacid reactive substances (TBARS), hydroperoxides, superoxide dismutase (SOD), catalase (CAT), glutathione peroxide (Gpx), reduced glutathione (GSH), glutathione-S-transferase (GST), and vitamins C and E were assayed in liver and kidney. Treatment with EMS and metformin to diabetic rats resulted in a significant reduction in plasma glucose, TBARS, and hydroperoxides. In addition, the treated groups also showed a significant increase in the activities of plasma insulin, SOD, CAT, GPx, GST, GSH, vitamin C, and vitamin E in liver and kidney of STZ-nicotinamide-induced diabetic rats. Our result suggest that non glucidic nutrient, such as EMS as a potent antidiabetic, may optimalize antiperoxidative and antioxidants status by restoring the biochemical alterations found in STZ-nicotinamide-induced type 2 diabetes.     

Attenuation of beryllium induced hepatorenal dysfunction and oxidative stress in rodents by combined effect of gallic acid and piperine

We determined a minimum effective dose of gallic acid (3,4,5-trihydroxy benzoic acid; 50 mg/ kg, i.p.) and piperine (10 mg/kg, p.o.) through their therapeutic potential and further evaluated them individually and in combination against beryllium-induced biochemical alterations and oxidative stress consequences in female albino rats. The administration of beryllium altered blood biochemical variables by significantly depleting hemoglobin, albumin and urea, whereas it enhanced bilirubin and creatinine. The release of serum transaminase, lactate dehydrogenase and gamma-glutamyl transpeptidase was significantly greater, and was concomitant with a decrease in serum alkaline phosphatase. A significant increase in lipid peroxidation and a decrease in glutathione, superoxide dismutase and catalase in the liver and kidney was an indication of oxidative stress due to beryllium exposure. Individual administration of gallic acid and piperine moderately reversed the altered biochemical variables, whereas the combination of these was found to completely reverse the beryllium-induced biochemical alterations and oxidative stress consequences. We concluded that gallic acid exerts a synergistic effect when administered with piperine and provides a more pronounced therapeutic potential in reducing beryllium-induced hepatorenal dysfunction and oxidative stress consequences.     

Protective effects of caffeic acid phenethyl ester on doxorubicin-induced cardiotoxicity in rats

The prevention of doxorubicin (DXR)-induced cardiotoxicity may be helpful to improve future DXR therapy. The aim of this study was to investigate the cardio-protective effects of caffeic acid phenethyl ester (CAPE), an antioxidant agent, on DXR-induced cardiotoxicity. Rats were divided into three groups and treated with saline, DXR and DXR + CAPE. Rats were treated with CAPE (10 micromol x kg(-1) day(-1) i.p.) or saline starting 2 days before a single dose of DXR (20 mg x kg(-1) i.p.). Ten days later, haemodynamic measurements were performed and the hearts were excised for biochemical analyses and microscopic examination. The heart rate and mean blood pressure were higher and the pulse pressure was lower in the DXR group than in the other two groups. The administration of DXR alone resulted in higher myeloperoxidase activity, lipid peroxidation and protein carbonyl content than in the other groups. The activities of superoxide dismutase and catalase were higher in DXR and DXR + CAPE groups than in the saline group. Rats in the DXR + CAPE group had increased catalase activity in comparison with the DXR group and high glutathione peroxidase activity in comparison with the other two groups. There was severe disruption of mitochondrial fi ne structure in the electron microscopy of the DXR group. In contrast, myocardial microscopy appeared nearly normal in the DXR + CAPE group (as de fi ned at the electron microscopic level). In light of these in vivo haemodynamic, enzymatic and morphological results, we conclude that CAPE pretreatment significantly attenuated DXR-induced cardiac injury, possibly with its antioxidant effects.     

Parachlorophenylalanine exacerbates oxidative stress induced by gentamicin in rats

The present work studies the effect of parachlorophenylalanine (PCPA, 200 mg/kg intraperitoneally/48 hr for 7 days) on the oxidative stress and nephropathy induced by gentamicin (80 mg/kg intraperitoneally/daily for 7 days) in Wistar rats. The effect of PCPA on lipid peroxidation products and reduced glutathione content in renal and brain tissue, as well as on 5HT content in brain was assessed. Catalase and superoxide dismutase activities were determined in brain tissue. Blood urea nitrogen and creatinine in plasma and total protein content in urine were also measured. Gentamicin caused significant increases in proteinuria, non-protein nitrogen compounds and lipid peroxidation markers, together with decreases in both reduced glutathione content in renal and brain tissue and enzymatic activities in brain homogenates. PCPA harnessed the effect of gentamicin in the brain and the kidney, while PCPA alone induced brain oxidative stress. These results support the prooxidant action of PCPA in brain tissue and its capacity to exacerbate the oxidative stress and renal dysfunction induced by gentamicin, as well as the possible antioxidant property of serotonin.     

Design,synthesis and pharmacological evaluation of caffeic acid phenethyl ester acylation as multifunctional neuroprotective agents against oxidative stress injury

4-Acylated or 3,4-diacylated caffeic acid phenethyl ester (CAPE) was prepared as prodrug to improve its stability and lipid solubility. Their neuroprotective activities were assessed by H2O2 model and 6-OHDA model. The results showed that target compounds displayed positive abilities to protect PC12 nerve cells from oxidative stress injury, superior to that of CAPE. Additionally, target compounds showed high blood-brain barrier permeability.     

Effects of caffeic acid phenethyl ester on glycerol-induced acute renal failure in rats

1. Free radicals and nitric oxide (NO) play a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). The aim of the present study was to investigate the effects of caffeic acid phenethyl ester (CAPE), an anti-oxidant, on the myoglobinuric ARF induced by intramuscular hypertonic glycerol injection. 2. Thirty rats were divided equally into three groups. Rats in group 1 were given saline and those in groups 2 and 3 were injected with glycerol (10 mL/kg, i.m.). Concomitant and 24 h after glycerol injection, CAPE (10 micromol/kg, i.p.) was administered to group 3 rats. Forty-eight hours after glycerol injection, blood samples and kidney tissues of rats were taken under anaesthesia. 3. Plasma concentrations of urea, creatinine, malondialdehyde (MDA) and NO were determined, as were superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities and MDA levels in kidney tissues. Kidney morphology was also investigated. 4. In the group receiving CAPE, although SOD enzyme activity was found to be increased, we failed to find any protective effect of CAPE on other parameters investigated. Moreover, although CAPE significantly decreased NO levels, it increased plasma concentrations of urea and MDA. 5. We suggest that the effect of CAPE in decreasing NO concentrations may further increase the renal ischaemia in this model. Thus, CAPE may have a worsening rather than beneficial effect under these conditions in this model of ARF.     

Tinospora cordifolia attenuates oxidative stress and distorted carbohydrate metabolism in experimentally induced type 2 diabetes in rats

Diabetes is a chronic metabolic disorder affecting a vast number of people worldwide. Oxidative stress is the causative agent amplifying diabetic complications in various organs by generating noxious amount of free radicals. A huge interest always exists in exploring nutraceuticals from plant materials to replace synthetic drugs in order to overcome their adverse effects and also for economic reasons. The anti-diabetic efficiency of a medicinal plant, Tinospora cordifolia (TC) was studied in experimentally induced type 2 diabetes in Sprague-Dawley rats. Diabetes was induced by a combination of high fat diet (HFD) for a period of 10 weeks followed by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg of body weight). Oral treatment of TC (100 and 200 mg/kg body weight) for 14 days regulated blood glucose, provoked insulin secretion and also suppressed oxidative stress marker, thiobarbituric acid reactive substances (TBARS), formation and restored cellular defence anti-oxidant markers including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH), in liver. Treatment with TC (100 and 200 mg/kg) also inhibited glucose 6-phosphatase and fructose 1,6-diphosphatase (p < 0.001); and restored glycogen content in liver (p < 0.005), which was also studied by histopathological staining with periodic acid-Schiff stain. In conclusion, the traditional plant Tinospora cordifolia mediates its anti-diabetic potential through mitigating oxidative stress, promoting insulin secretion and also by inhibiting gluconeogenesis and glycogenolysis, thereby regulating blood glucose.     

Effects of melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism

1. The present study was designed to investigate the effects of high-dose melatonin on lipid peroxidation and anti-oxidant enzyme activity in rats with experimentally induced hyperthyroidism. 2. Twenty-four albino male rats, weighing 240-260 g, were randomly allotted into one of three experimental groups (control, hyperthyroid and hyperthyroid + melatonin treatment), with each group containing eight animals. Hyperthyroidism was induced by a daily with i.p. injection of 200 microg l-thyroxine for 30 days. In addition to l-thyroxin treatment, rats in the hyperthyroid + melatonin treatment group were also given daily i.p. injections of 10 mg/kg melatonin on the last 10 days of l-thyroxine treatment. Control animals received injections of an equivalent volume of saline solution. Rats received the last injection 24 h before being killed. 3. At the end of the experiment, rats in all three groups were fasted for 12 h and killed by cardiac puncture under ether anaesthesia. Blood samples were taken for the determination of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels and concentrations of tri-iodothyronine (T(3)) and thyroxine (T(4)). 4. It was found that MDA and SOD levels and concentrations of T(3) and T(4) were higher and the GSH level was lower in rats with hyperthyroidism compared with controls. Melatonin treatment decreased the elevated MDA and SOD levels and increased the lowered GSH level to control levels in rats with hyperthyroidism, but did not ameliorate the concentrations of T(3) and T(4). 5. It was concluded that high-dose melatonin treatment may decrease the hyperthyroidism-induced disturbances of lipid peroxidation and anti-oxidant enzyme activity and oxidative damage.     

Effects of salvianolic acid a on oxidative stress and liver injury induced by carbon tetrachloride in rats

In the present study, we investigated the hepatoprotective effects of salvianolic acid A, a novel antioxidant, against oxidative stress and acute liver injury induced by carbon tetrachloride (CCl(4)) in rats, and the mechanisms underlying its protective effects. Administration of CCl(4) to rats caused severe hepatic damage, as demonstrated by the significant increase in the levels of serum alanine aminotransferase, aspartate aminotransferase and classic histological changes including hepatocyte necrosis or apoptosis, haemorrhage, fatty degeneration, etc. Co-treatment with salvianolic acid A (20 mg/kg, intraperitoneally), a water-soluble extract from a Chinese traditional drug, Radix Salvia miltiorrhiza, significantly decreased CCl(4)-induced hepatotoxicity. Salvianolic acid A not only decreased serum alanine aminotransferase, aspartate aminotransferas levels and ameliorated histopathological manifestations in CCl(4)-treated rats, but also reduced oxidative stress, as evidenced by decreased reactive oxygen species production and malondialdehyde concentrations in the liver tissues, combined with elevated hepatic superoxide dismutase activity and gluthathione content. In addition, salvianolic acid A treatment remarkably reduced intrahepatic tumour necrosis factor-alpha concentrations and caspase-3 activities as compared with the CCl(4)-treated rats. The results suggested that treatment with salvianolic acid A provides a potent protective effect against acute hepatic damage caused by CCl(4) in rats, which may mainly be related to its antioxidative effect.     

Effect of caffeic acid and rofecoxib and their combination against intrastriatal quinolinic acid induced oxidative damage, mitochondrial and histological alterations in rats

Oxidative stress has long been implicated in the neurotoxic effects of glutamate acting through N-methyl-D-aspartate (NMDA) receptors. Therefore, present study has been designed to explore the effect of rofecoxib and caffeic acid on the involvement of oxidative stress, mitochondrial dysfunction and neuronal linked with NMDA receptor-mediated excitotoxicity. Caffeic acid, is a well-known antioxidant flavanoid, implicate anti-inflammatory and immunomodulatory like actions. The present study is an attempt to investigate the antioxidant-like effect of caffeic acid and rofecoxib and their combination against QA-induced oxidative damage, mitochondrial dysfunction and histological alterations. Intrastriatal injection of quinolinic acid (300 nmol) significantly increased oxidative stress (raised lipid peroxidation, nitrite concentration, depleted SOD and catalase), altered mitochondrial complex enzyme activities and histological alteration in the ex vivo striatum. Caffeic acid (5 and 10 mg/kg, p.o.) and rofecoxib (10 and 20 mg/kg, p.o.) treatment for 21 days significantly attenuated oxidative damage and impairment in mitochondrial activities of complex enzymes in the ex vivo striatum. Further, combination of sub effective doses of rofecoxib (10 mg/kg, p.o.) and caffeic acid (5 mg/kg, p.o.) potentiated their protective effect which was significant as compared to their effect per se. The present study suggests the therapeutic effect of caffeic acid and rofecoxib combination against QA-induced ex vivo oxidative damage, mitochondrial and histological alterations in rats.     

咖啡酸对慢性铝过负荷致大鼠脑损伤的保护作用

目的探讨5-LO抑制剂咖啡酸对慢性铝过负荷致大鼠脑损伤的保护作用。方法灌胃给予大鼠葡萄糖酸铝(Al3+200mg.kg-1),1d1次,每周5d,持续20wk,建立慢性铝过负荷致大鼠脑损伤、神经元退变动物模型;5-LO抑制剂咖啡酸(30、10mg.kg-1)分别在每次大鼠铝给予1h后灌胃。以大鼠空间学习记忆能力改变、海马病理形态学变化以及脑组织MAO-B、AChE、SOD活性和MDA含量变化为观察指标。结果铝过负荷明显导致大鼠空间学习记忆能力下降、海马神经元损伤、脑组织MDA含量明显升高、MAO-B和AChE活性明显升高、SOD活性明显降低。给予咖啡酸能明显改善慢性铝过负荷大鼠的学习记忆能力障碍,明显减轻铝过负荷大鼠海马神经细胞的损伤,明显阻遏铝过负荷大鼠海马MDA含量的增加、AChE和MAO-B活性升高以及SOD活性的降低。结论5-LO抑制剂咖啡酸对慢性铝过负荷大鼠脑脑损伤、神经元退变有明显的保护作用。     

The protective effect of caffeic acid phenethyl ester against cyclosporine A-induced cardiotoxicity in rats

Cyclosporine A (CsA) is the immunosuppressor, which is most frequently used in transplant surgery and in the treatment of autoimmune diseases. Oxidative stress has been considered as one of the possible mechanisms of CsA-induced cardiotoxicity. The present investigation examines the ability of caffeic acid phenethyl ester (CAPE), which is an active component of propolis extracts, as a natural antioxidant to protect against CsA-induced oxidative stress and cardiotoxicity. CsA cardiotoxicity was induced by subcutaneous injection of CsA at a dose of 15 mg/kg/body weight daily for 21 days in rats. Cardiotoxicity was evaluated by morphological and biochemical studies. CsA treated rats showed degenerative changes with cardiac fibrosis localized around the fibers. These latters were disorganised and the network was disappeared. The ROS production was increased whereas cytochrome-c-oxidase decreased. The expression and levels of matrix metalloproteinase 2 (MMP2) were increased whereas those of its inhibitor were downregulated. CAPE subcutaneous administration (15 micromol/kg/day) improved cardiac cytoarchitecture, decreased the levels and the expression of MMP2, and increased those of TIMP2 proteins. Moreover, it increased cytochrome-c-oxidase activity and decreased ROS production. These results suggest that CAPE could have protective effect against CsA-induced cardiotoxicity.     

Correlation of testicular toxicity and oxidative stress induced by chlorpyrifos in rats

Effect of chlorpyrifos pesticide on testicular oxidative damage was studied in Sprague-Dawley rats at varying doses. At lower doses (5 and 10 mg/kg body weight/30 days), reduction in plasma levels of testosterone and follicular stimulating hormone (FSH) and luteinizing hormone (LH) along with significant shrinkage of seminiferous tubules and drastic changes in germ cells were seen. But these adverse changes of testes were restored with the revival of serum testosterone and FSH and LH at higher doses (20 and 30 mg/kg body weight/30 days). Similarly, levels of testicular lipid peroxidation and diene conjugates were elevated whereas activities of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase), steroidogenic (Δ(5), 3β-HSD and Δ(5), 17β-HSD) enzymes and angiotensinogen-converting enzyme and glutathione content including lipid-protein content of testes were decreased at low doses. But at higher doses, reductions in level of lipid peroxidation (as revealed by malondialdehyde [MDA] value) and conjugated dienes were found and on the contrary, revivals of testicular antiperoxidative/antioxidant enzymes defense systems, angiotensinogen-converting enzyme (ACE), steroidogenic enzymes, lipid-protein and antioxidant glutathione content were observed. Therefore, the present study indicated from the results that chlorpyrifos had a dual effect at both doses on oxidative stress changes, but at higher doses, the cells were triggering its natural defense mechanism to combat the insult of lower doses of chlorpyrifos and became operative possibly through corrective measure of antioxidant enzymes defense system and pituitary gonadotropins hormones feedback mechanisms on testes.     

Treatment with dehydroepiandrosterone prevents oxidative stress induced by 3-nitropropionic acid in synaptosomes

This study evaluates the antioxidative effect of dehydroepiandrosterone (DHEA) treatment on 3-nitropropionic acid (3-NPA)-induced oxidative stress in striatal and brain cortex synaptosomes. The oxidative derangement was confirmed by a high level of lipid peroxidation products and protein carbonyls, as well as by an enhanced superoxide dismutase activity (p < 0.001). These changes were partially prevented by DHEA. Moreover, 3-NPA induced a drop in succinate dehydrogenase activity, while DHEA treatment restored the succinate dehydrogenase activity. These results show that DHEA reduces oxidative stress in synaptosomes isolated from the brain of 3-NPA-treated rats, and they suggest this neurosteroid may protect mitochondrial and maintain synaptic integrity against damage induced by this acid.     

Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats

Metabolic syndrome and oxidative stress are common complications of type 2 diabetes mellitus. The present study was designed to determine whether resveratrol, a widely used nutritional supplement, can improve insulin sensitivity, metabolic complication as well as hepatic oxidative stress in fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four groups with 8 animals each. Fructose-fed insulin resistant group (Dia) animals were fed 65% fructose (Research diet, USA) for a period of 8 weeks, whereas control group (Con) animals were fed 65% cornstarch (Research Diet, USA). Resveratrol, 10 mg/kg/day (Dia+Resv) or metformin 300 mg/kg/day (Dia+Met) were administered orally to the 65% fructose-fed rats for 8 weeks. At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels. Significant (p<0.05) increase in hepatic TBARS and conjugated dienes, and significant (p<0.05) decrease in hepatic SOD and vitamin C was observed in Dia group compared to Con group. Administration of metformin or resveratrol significantly (p<0.05) normalized all the altered metabolic parameters. However, a marked insulin sensitizing action was only observed in the Dia+Resv group. Similarly, while metformin administration failed to normalize the increased TBARS levels and decreased SOD activity, resveratrol showed a more promising effect of all oxidative stress parameters measured in the present study. Attenuation of hepatic oxidative stress in fructose-fed rat liver after resveratrol administration was associated with significant (p<0.05) increase in nuclear level of NRF2 compared with other groups. The present study demonstrates that resveratrol is more effective than metformin in improving insulin sensitivity, and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.