Testicular protective effects of ellagic acid on monosodium glutamate-induced testicular structural alterations in male rats

ABSTRACT

Ellagic acid (EA) has significant protective and antioxidant effects on several tissues. Monosodium glutamate (MG) is known as a flavor promoter that reversibly influences the male reproductive system. This study aims to assess the ameliorative effect of EA on oxidative stress and testicular damage induced by MG. In total, 48 male rats were included in this study and separated into six groups: control, EA (20 mg/kg), MG (low dose) (17.5 mg/kg), MG (high dose) (60 mg/kg), MG (low dose) combined with EA, and MG (high dose) combined with EA. Testicular antioxidant biomarkers [superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GRx), catalase (CAT), myeloperoxidase (MPO), and xanthine oxidase (XO)] were examined. Testes were examined and scored for histological variation as an indicator of testicular damage following administration of MG alone or in combination with EA. Serum testosterone, inhibin B, 8-hydroxydeoxyguanosine (as a marker of DNA damage), and transmission electron microscope sections of the testis were evaluated, and a comet assay was performed. Results showed that administration of EA combined with MG significantly elevated the levels of enzymatic antioxidants and decreased lipid peroxidation compared with MG treatment alone. EA elevated testosterone hormone levels and thus enhanced male reproductive capacity. It is clear from the data that EA inhibits histological and ultrastructure testicular damage and improves the redox state in male rats.     

The effects of combined alpha-tocopherol, ascorbic acid, and selenium against cadmium toxicity in rat intestine.

In this study, the effects of combined antioxidants treatment against cadmium toxicity were investigated microscopically, immunohistochemically, and biochemically in small intestine of Sprague Dawley rats. The rats were subdivided into four groups as intact control, cadmium was administrated, and both control and cadmium groups treated with ascorbic acid, alpha-tocopherol, and selenium. Metallothionein expression was localized in the base of intestinal glands in control rats and similar expression was observed with antioxidants treatment. In cadmium-administrated rats, metallothionein expression was detected in surface epithelium, longitudinal muscle layer, meissner, and myenteric plexuses, but not in the base of intestinal gland. On the other hand, in the rats treated with antioxidants and cadmium, immunreactivity increased in the surface epithelium and in the base of intestinal glands according to cadmium-administrated rats but not changed in the plexuses and longitudinal muscle layer. Biochemically, lipid peroxidation levels increased and glutathione levels decreased significantly in intestine of the cadmium group compared to the control. Treatment with antioxidants in cadmium-administrated rats led to a decrease in lipid peroxidation levels and a significant increase in glutathione levels. As a result, the combination of ascorbic acid, alpha-tocopherol, and selenium shows a protective effect against cadmium toxicity in small intestine.     

糖尿病大鼠睾丸病理变化及脂质过氧化和一氧化氮的改变

目的:研究糖尿病睾丸的病理变化及其发生机制。方法:用光镜及透射电镜观察四氧嘧啶诱导的糖尿病1个月大鼠睾丸的形态学改变,并测定睾丸组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、一氧化氮合酶(NOS)的活性及一氧化氮(NO)、丙二醛(MDA)含量。结果:光镜下主要表现为睾丸曲细精管萎缩及生精阻滞;透射电镜下主要见到支持细胞线粒体与内质网扩张、胞浆内内含物形成;睾丸组织的SOD、GSH-PX活性实验组低于对照组,NOS活性及NO、MDA含量实验组高于对照组。结论:糖尿病大鼠睾丸病变主要为支持细胞受损及生精障碍,其可能与脂质过氧化作用及NO所致的损伤有关。     

Dexamethasone mediated downregulation of PGC-1α and visfatin regulates testosterone synthesis and antioxidant system in mouse testis

Dexamethasone, a synthetic glucocorticoid has been used as an immunosuppressive and anti-inflammatory and affects reproduction. It has been suggested that testicular steroidogenesis involves PGC-1α and visfatin as key regulators. Previous studies have shown that dexamethasone down-regulates PGC-1α and visfatin expression in muscle and mammary epithelial cells respectively. However, the effect of dexamethasone on testicular visfatin and PGC-1α expressions has not been investigated. The aims of the present study were to investigate the effect of dexamethasone, on the expression of PGC-1α, visfatin and antioxidant enzymes activities in mouse testis. The results of the present study showed that dexamethasone treatment significantly decreased the expression of visfatin and PGC-1α in mice testis, along with significant decreased in testicular antioxidant enzymes activates. Further, dexamethasone treatment also significantly increased the testicular lipid peroxidation and decreased testosterone synthesis. The dexamethasone induced changes in PGC-1α and visfatin in the testis were significantly correlated with changes in serum testosterone concentrations and antioxidant enzymes activities. Thus, dexamethasone induced testicular toxicity may involve the PGC-1α and visfatin as important molecules to exhibit its effects.     

Prevention of cisplatin-induced nephrotoxicity by glucosides of ascorbic acid and alpha-tocopherol

BACKGROUND: Cisplatin is one of the most widely used cytotoxic therapeutic agents for the treatment of cancer. This drug, at effective higher doses, causes many physiological adverse effects such as nephrotoxicity and genotoxicity. The toxicity of the drug has been attributed to the induction of oxidative free radicals. METHODS: Following intraperitoneal administration of cisplatin and ascorbic acid monoglucoside (AsAG) or alpha-tocopherol monoglucoside (TMG), investigations were conducted on levels of serum urea and creatinine, peroxidation of lipids in renal tissues, renal antioxidants and histopathology of renal tissue. RESULTS: Administration of cisplatin to mice induced a marked renal failure, characterized by significant increase in serum urea and creatinine levels in addition to severe alterations in renal tissue architecture. Cisplatin also induced oxidative stress as indicated by increased lipid peroxidation and decreased levels of reduced glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase in renal tissues. Administration of AsAG or TMG markedly reduced the cisplatin-induced higher plasma creatinine and urea levels and counteracted the deleterious effects of cisplatin on oxidative stress markers and protected the tissues from the cisplatin-induced lipid peroxidation. CONCLUSION: These results indicated that AsAG or TMG has a protective effect against cisplatin-induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of AsAG or TMG in human application for protecting against drug-induced nephrotoxicity.     

Low dose of 2,3,7,8 tetrachlorodibenzo-p-dioxin induces testicular oxidative stress in adult rats under the influence of corticosterone

2,3,7,8 Tetrachlorodibenzo-p-dioxin (TCDD), an endocrine disruptor, causes testicular toxicity by increasing the production of reactive oxygen species (ROS). Glucocorticoids have been reported to influence TCDD action in vitro. Stress, characterized by increased glucocorticoid levels, has been found to suppress the testicular function. The present experiments were set up to analyse the effects of a low dose of TCDD on the rat testis under the influence of increased corticosterone levels. TCDD (1 ng/kg b.w./day) and corticosterone (3 mg/kg b.w./day) were administered alone or together to adult male rats for 15 days. Corticosterone administration raised the levels of serum corticosterone and decreased the levels of serum testosterone significantly. In the testicular mitochondrial- and microsomal-rich fractions, corticosterone administration increased the levels of lipid peroxidation and hydrogen peroxide and decreased the activities of antioxidant enzymes like superoxide dismutase and catalase significantly. TCDD administration to rats treated with corticosterone decreased the levels of serum testosterone as compared to rats treated with corticosterone alone. The levels of lipid peroxidation and hydrogen peroxide increased and the activities of superoxide dismutase and catalase were decreased significantly in mitochondrial- and microsomal fractions of the testis of treated rats as compared to those treated with corticosterone alone. It is concluded that stress may enhance the effects of TCDD on the testis.     

Expression of visfatin in alloxan-induced diabetic rat testis

Diabetes mellitus is a potential epidemic all over the world and causes dysfunction of reproductive activity. Visfatin, one of the adipokines, is present in various tissues including the testis. Our hypothesis was the level of testicular visfatin is affected in diabetic condition. The aim of the present study was to investigate the expression and localization of visfatin in the diabetic rat testis. No similar studies have been performed in diabetic rat testis with reference to visfatin. Overnight fasted adult male Wistar rats were made diabetic by the administration of alloxan (150 mg/kg i.p., in 0.9% saline). Blood glucose levels were tested on five days after alloxan treatment, rats with high blood glucose levels (>250 mg/dL) were considered as diabetic. Immunolocalization and Western blotting analysis of visfatin were performed. Correlation of visfatin expression was made in relation to body weight, testis weight, glucose concentration and serum testosterone level. Expression of visfatin was observed in Leydig cells, spermatocytes and sperm in control as well as in the diabetic group. Mild immunostaining of visfatin was observed in affected seminiferous tubules of alloxan-induced diabetic rat testis. Western blot analysis showed decreased expression of testicular visfatin in diabetic rats. The expression of visfatin showed a positive correlation with serum testosterone levels, body and testis weight, while a negative correlation was observed with blood glucose levels. This study showed involvement of visfatin in diabetic associated impairment of testicular activity.     

Effect of monensin on the enzymes of oxidative stress, thiamine pyrophosphatase and DNA integrity in rat testicular cells in vitro.

Monensin, a sodium specific ionophore was evaluated for its in vitro effects on rat testis by studying changes at biochemical parameters as well as at the DNA level. It was observed that monensin produced marked alterations in the activities of various enzymes associated with the testicular functions. The significant inhibition of different enzymes of oxidative defense system points toward the generation of reactive oxygen species (ROS) by monensin treatment. The significant depletion of reduced glutathione and elevation in the level of lipid peroxidation further support the above findings. The significant inhibition of the activities of lactate dehydrogenase and adenosine triphosphatase shows the interference of monensin with the normal energy supply in spermatogenesis. Moreover, the significant increase in the activities of acid phosphatase and thiamine pyrophosphatase demonstrates the interference of monensin with the Golgi-lysosomal complex of the rat testis. Induced DNA fragmentation indicates towards the impact of monensin on the DNA integrity and apoptosis. Further studies are needed to understand the important molecular mechanisms responsible for these effects.     

Impact of ellagic acid on adriamycin-induced testicular histopathological lesions,apoptosis, lipid peroxidation and sperm damages

The aim of the present study was to investigate whether ellagic acid (EA) has protective effect on adriamycin (ADR)-induced testicular and spermatozoal toxicity associated with the oxidative stress in male rats. Thirthy-two healthy 8-week-old male Sprague–Dawley rats were equally divided into four groups. The first (EA) group was treated with EA (2 mg/kg/every other day) by gavage. The second (ADR) group received ADR (2 mg/kg/once a week) intraperitoneally, while the combination of ADR and EA was given to the third (ADR + EA) group. The forth (control) group was treated with placebo. At the end of the 8-week treatment period, reproductive organ weights, epididymal sperm parameters, histopathological changes and apoptosis via Bax and Bcl-2 proteins, testicular tissue lipid peroxidation, and antioxidant enzyme activities, were investigated. ADR administration was determined to cause significant decreases in reproductive organ weights, epididymal sperm concentration and motility, plasma testosterone concentration, diameter of seminiferous tubules, germinal cell layer thickness, Johnsen's testicular score and Bcl-2 positive antiapoptotic cell rate, wherease it caused significant increases in level of lipid peroxidation and glutathione, catalase activity, abnormal sperm rates and Bax positive apoptotic cell rates along with degeneration, necrosis, immature germ cells, congestion and atrophy in testicular tissue when compared with the control group. EA administration to ADR-treated rats provided significant improvements in ADR-induced disturbed oxidant/antioxidant balance, decreased testosterone concentration, testicular apoptosis and mild improvements in the histopathological view of the testicular tissue. However, EA failed to improve decreased reproductive organ weights and deteriorated sperm parameters due to ADR administration. It is concluded that while ADR has direct or indirect (lipid peroxidation) negative effects on sperm structure and testicular apoptosis in rats, EA has protective effects on ADR-induced testicular lipid peroxidation and apoptosis.     

Protective effect of ellagic acid against cyclosporine A-induced histopathological,ultrastructural changes,oxidative stress,and cytogenotoxicity in albino rats

Cyclosporine A (CsA) is an immunosuppressor agent, which is most frequently used in transplant surgeries and in the treatment of autoimmune diseases. This study was undertaken to investigate the protective effects of ellagic acid (EA) against CsA-induced testicular histopathology and ultrastructure changes, oxidative stress, and cytogenotoxicity in male albino rats. Rats were divided into six groups; the first group was used as a control, the second group received a subcutaneous injection of slightly alkaline solution, the third group received olive oil orally, the fourth group was injected subcutaneously with EA at a dose of 10 mg/kg b. wt./day, the fifth group was treated with CsA as oral solution at a dose of 15 mg/kg b. wt for 30 days, and the sixth group was treated with CsA simultaneously with EA. Treatment with EA simultaneously with CsA resulted in significant protection. The positive control animals taking CsA alone showed marked histopathological, ultrastructure, and genetic manifestations accompanied by an elevated content of lipid peroxidation and marked reduction of catalase (CAT), peroxidase (Px) activity, and glutathione concentration in the homogenate of testis tissues. The toxic side effects in testis and bone marrow tissues were greatly ablated with a significant reduction in lipid peroxidation level and elevation in CAT and Px activities and glutathione concentration when using EA. Thus, EA may be used in combination with CsA to improve the histopathological, oxidative stress, and cytogenotoxicity parameters of testicular toxicity induced by CsA due to its antioxidant effects.     

Effect of pretreatment of salt, copper and temperature on ultraviolet-B-induced antioxidants in diazotrophic cyanobacterium Anabaena doliolum

Effect of salt, copper, and temperature pretreatments on the UV-B-induced oxidative damage, measured in terms of peroxide and MDA (lipid peroxidation) contents, was studied in the diazotrophic cyanobacterium Anabaena doliolum. To understand the survival strategy enzymatic (superoxide dismutase, catalase, glutathione reductase, and ascorbate peroxidase) and non-enzymatic (glutathione, ascorbate, alpha-tocopherol and carotenoid) antioxidants were studied. Among the various pretreatments salt was found to decrease and copper and temperature pretreatments increased the deleterious effects of UV-B. This study is the first to demonstrate that physical stress (high temperature) enhanced the damaging effect of UV-B more profoundly than chemical stresses (salt and copper).     

Time course of oxidative damage in different brain regions following transient cerebral ischemia in gerbils.

The time course of oxidative damage in different brain regions was investigated in the gerbil model of transient cerebral ischemia. Animals were subjected to both common carotid arteries occlusion for 5 min. After the end of ischemia and at different reperfusion times (2, 6, 12, 24, 48, 72, 96 h and 7 days), markers of lipid peroxidation, reduced and oxidized glutathione levels, glutathione peroxidase, glutathione reductase, manganese-dependent superoxide dismutase (MnSOD) and copper/zinc containing SOD (Cu/ZnSOD) activities were measured in hippocampus, cortex and striatum. Oxidative damage in hippocampus was maximal at late stages after ischemia (48-96 h) coincident with a significant impairment in glutathione homeostasis. MnSOD increased in hippocampus at 24, 48 and 72 h after ischemia, coincident with the marked reduction in the activity of glutathione-related enzymes. The late disturbance in oxidant-antioxidant balance corresponds with the time course of delayed neuronal loss in the hippocampal CA1 sector. Cerebral cortex showed early changes in oxidative damage with no significant impairment in antioxidant capacity. Striatal lipid peroxidation significantly increased as early as 2 h after ischemia and persisted until 48 h with respect to the sham-operated group. These results contribute significant information on the timing and factors that influence free radical formation following ischemic brain injury, an essential step in determining effective antioxidant intervention.     

Oxidative stress induced by fluoride in adult mice and their suckling pups.

To assess renal and liver damages in pregnant and lactating mice as well as in their suckling pups, Wistar female mice were given 500 ppm NaF (226 ppm F-) in drinking water from the 15th day of pregnancy until day 14 after delivery. All mice were sacrificed on day 14 after parturition. In the present work, we evaluated the effects of sodium fluoride on histopathological aspects of kidney, antioxidant status, lipid peroxidation levels and on the expression of four stress proteins (namely, the cytosolic heat shock proteins: HSP72, 73, 90 and the reticulum-associated GRP94). Histological studies have shown many abnormalities in mothers and their pups. Biochemical results showed that lipid peroxidation increased in NaF-treated mice, as evidenced by high kidney and liver thiobarbituric acid reactive substance (TBARS) levels. Alteration of the antioxidant system was confirmed by the significant decline of serum total antioxidant status and of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in red blood cells. Besides, fluoride treatment induced a decrease in serum levels of non-enzymatic antioxidants such as uric acid and of some oligoelements: zinc and copper, known to be cofactors of superoxide dismutase (SOD-Cu-Zn). Compared to control group, the 72kDa protein was found to be overexpressed in kidney of 14-day-old mice only. HSP90 expression in liver appeared moderately inhibited in mothers, but decreased significantly in their pups. No significant changes were detected in the expression of 94kDa protein in both liver and kidney. Results showed that fluoride given to dams led to an oxidative stress in mothers as well as in offspring able to induce enhanced lipid peroxidation levels and protein conformational changes, as suggested by stress protein (HSP, GRP) expression changes.     

Cadmium-induced hepatotoxicity in rats and the protective effect of naringenin

This experiment pertains to the protective role of naringenin against cadmium (Cd)-induced oxidative stress in the liver of rats. Cadmium is a major environmental pollutant and is known for its wide toxic manifestations. Naringenin is a naturally occurring citrus flavonone which has been reported to have a wide range of pharmacological properties. In the present investigation cadmium (5 mg/kg) was administered orally for 4 weeks to induce hepatotoxicity. Liver damage induced by cadmium was clearly shown by the increased activities of serum hepatic marker enzymes namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma glutamyl transferase (GGT) and serum total bilirubin (TB) along with the increased level of lipid peroxidation indices (thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides) and protein carbonyl contents in liver. The toxic effect of cadmium was also indicated by significantly decreased levels of enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione S-transferase (GST)) and non-enzymatic antioxidants (reduced glutathione (GSH), vitamin C and vitamin E). Administration of naringenin at a dose of (50 mg/kg) significantly reversed the activities of serum hepatic marker enzymes to their near-normal levels when compared to Cd-treated rats. In addition, naringenin significantly reduced lipid peroxidation and restored the levels of antioxidant defense in the liver. The histopathological studies in the liver of rats also showed that naringenin (50 mg/kg) markedly reduced the toxicity of cadmium and preserved the normal histological architecture of the tissue. The present study suggested that naringenin may be beneficial in ameliorating the cadmium-induced oxidative damage in the liver of rats.     

Fenugreek seed powder mitigates cadmium-induced testicular damage and hepatotoxicity in male rats

Cadmium is a potential environmental and industrial pollutant affecting human tissues and organs including liver and testes. The protective role of fenugreek seed powder (FSP) was investigated in male rats subjected to cadmium-induced testicular injury and hepatic dysfunction. Testicular damage and hepatotoxicity were induced by oral administration of cadmium chloride (5 mg/kg body weight, once a day) for 7 weeks. FSP was given at 5% w/w in chow diet for 8 weeks, starting 1 week before cadmium administration. FSP intake significantly increased serum testosterone level and testis weight that were reduced by cadmium. FSP also compensated deficits in hepatic and testicular antioxidant defense system, interleukin-4 and nitric oxide levels, reduced serum liver function enzyme activities and suppressed lipid peroxidation in hepatic and testicular tissues resulted from cadmium administration. Additionally, FSP attenuated the cadmium-induced elevations in hepatic and testicular tumor necrosis factor-α and transforming growth factor-beta1 levels as well as cadmium deposition and hydroxyproline content. The protective effect afforded by FSP was mainly due its antioxidant, antifibrotic and anti-inflammatory effects. In conclusion, the results of the present work indicated that FSP may represent a promising medicinal herb to protect hepatic and testicular tissues from the detrimental effects of cadmium.     

Overexpression of human copper/zinc superoxide dismutase in transgenic mice attenuates oxidative stress caused by methylenedioxymethamphetamine (Ecstasy).

Administration of 3,4-methylenedioxymethamphetamine (4 x 20 mg/kg) to non-transgenic CD-1 mice caused marked depletion in dopamine, 3,4-dihydroxyphenylacetic acid and 5-hydroxytryptamine in the caudate-putamen. There were no significant changes in serotonergic markers in the hippocampus and frontal cortex. Homozygous and heterozygous copper/zinc superoxide dismutase transgenic mice show partial protection against the toxic effects of 3,4-methylenedioxymethamphetamine on striatal dopaminergic markers. In addition, 3,4-methylenedioxymethamphetamine injections caused marked decreases in copper/zinc superoxide dismutase activity in the frontal cortex, caudate-putamen and hippocampus of wild-type mice. Moreover, there were concomitant 3,4-methylenedioxymethamphetamine-induced decreases in catalase activity in the caudate-putamen and hippocampus, decreases in glutathione peroxidase activity in the frontal cortex as well as increases in lipid peroxidation in the frontal cortex, caudate-putamen, and hippocampus of wild-type mice. In contrast, administration of 3,4-methylenedioxymethamphetamine to homozygous superoxide dismutase transgenic mice caused no significant changes in antioxidant enzyme activities nor in lipid peroxidation. These results provide further substantiation of a role for oxygen-based radicals in 3,4-methylenedioxymethamphetamine-induced neurotoxicity. The present data also suggest that free radicals generated during 3,4-methylenedioxymethamphetamine administration may perturb antioxidant enzymes. Consequently, there might be further overproduction of free radicals with associated peroxidative damage to cell membranes and associated terminal degeneration.     

The fatty acid composition of red cells deficient in glucose-6-phosphate dehydrogenase and their susceptibility to lipid peroxidation

Summary Oxidant damage to red cell membranes could play a part in the pathogenesis of acute and chronic haemolysis in glucose-6-phosphate dehydrogenase deficiency. Therefore, we studied the substrate for red cell membrane lipid peroxidation, i.e. the content of various polyunsaturated fatty acids in ghosts, and the susceptibility of red cells to lipid peroxidation in normal subjects and in subjects deficient in glucose-6-phosphate dehydrogenase. The fatty acid composition of red cell membranes and plasma was analysed by capillary column gas chromatography. The sensitivity of red cells to lipid peroxidation was evaluated after hydrogen-peroxide-induced oxidant stress. The degree of lipid peroxidation was monitored by measuring the release of pentane and ethane formed during the breakdown of n-6 and n-3 fatty acids. The red cell sensitivity to lipid peroxidation was found to be higher in subjects with glucose-6-phosphate dehydrogenase deficiency than in normal subjects. In the former, saturated fatty acids, in particular palmitic and stearic acid, were found to be decreased, whereas the proportion of arachidonic acid showed a clear increase. Fatty acid analysis of plasma did not reveal significant abnormalities in enzyme-deficient patients, which could explain the alteration of membrane fatty acids. Our results suggest that the increased content of substrate for lipid peroxidation, particularly arachidonic acid, in red cell membranes of subjects deficient in glucose-6-phosphate dehydrogenase, should be considered in an evaluation of an enhanced sensitivity to red cell lipid peroxidation.Abbreviations G-6-PD Glucose-6-phosphate dehydrogenase - GSH Reduced glutathione - GSSG oxidized glutathione - MCV Mean corpuscular volume - MDA Malondialdehyde - RBC Red blood cells - TBA Thiobarbituric acid     

Oxidative stress in autism

Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased in this disease. Levels of major antioxidant serum proteins, namely transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein), are decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously acquired language skills in children with autism. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper metabolism in autism. The membrane phospholipids, the prime target of ROS, are also altered in autism. The levels of phosphatidylethanolamine (PE) are decreased, and phosphatidylserine (PS) levels are increased in the erythrocyte membrane of children with autism as compared to their unaffected siblings. Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental and genetic factors may increase vulnerability to oxidative stress in autism. Taken together, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed.     

Glutathione and ascorbic acid enhance recovery of Guinea pig spinal cord white matter following ischemia and acrolein exposure.

OBJECTIVE: We have shown that acrolein, a lipid peroxidation byproduct, can inflict significant damage in isolated spinal cord white matter following oxygen glucose deprivation (OGD). The mechanism of such acrolein-induced damage is unclear. The aim of this study was to examine whether glutathione (GSH) and ascorbic acid, two reactive oxygen species (ROS) scavengers, can alleviate functional and anatomical damage due to acrolein. METHODS: We used an OGD injury model with isolated guinea pig spinal cord white matter. Sucrose gap recording was used to monitor axonal impulse conduction, and a horseradish peroxidase exclusion test was employed to determine membrane integrity. The functional and anatomical parameters were compared in three groups: acrolein, acrolein/GSH and acrolein/ascorbic acid. RESULTS: We found that while GSH resulted in an 87% recovery of compound action potential conductance, ascorbic acid produced a 97% recovery, compared with a 69% recovery in an injured group without treatment. It is noted that GSH, and to a lesser extent ascorbic acid, preferentially enhanced functional recovery in smaller axons. CONCLUSION: Acrolein-induced neuronal damage is likely mediated by ROS. Furthermore, GSH and ascorbic acid are effective in suppressing acrolein and free radical-induced injury in spinal cord white matter.     

Protective effect of curcumin on cypermethrin-induced oxidative stress in Wistar rats

The aim of present study was to investigate the protective effect of curcumin on cypermethrin-induced changes in blood biochemical markers and tissue antioxidant enzyme in rats. Rats were divided into six groups of six each: group I used as control and II and III groups were used as vehicle control. While, groups IV, V and VI were orally treated with curcumin (100 mg/kg body weight), cypermethrin (25 mg/kg body weight) and cypermethrin plus curcumin, respectively for 28 days. Serum biochemical markers were measured in the serum, and the levels of lipid peroxidation and antioxidant enzyme activity were determined in the liver, kidney and brain. Cypermethrin administration caused elevated level of blood biochemical markers in serum and lipid peroxidation in liver, kidney and brain. While the activities of non-enzymatic and enzymatic antioxidants levels were decreased except superoxide dismutase in liver, kidney and brain tissues. The presence of curcumin with cypermethrin significantly decreased the blood biochemical markers and lipid peroxidation but significantly increased the reduced glutathione, catalase and glutathione peroxidase level and preserved the normal histological architecture of the liver, kidney and brain. Our results indicate that curcumin can be potent protective agent against cypermethrin-induced biochemical alterations and oxidative damage in rats.