Possible involvement of nitric oxide in antidepressant-like effect of silymarin in male mice

Abstract

Context: Silymarin (SM) is extracted from milk thistle Silybum marianum L. [Asteraceae (Compositae)] and known for antioxidative and anti-inflammatory effects.

Objective: The potential antidepressant-like effect of acute SM and possible involvement of nitric oxide (NO) were determined in male mice.

Material and methods: SM was administered orally (5, 10, 20, 50, 100, and 200?mg/kg; p.o.) 60?min before the tests. After assessment of locomotor activity, the immobility time was measured in forced swimming test (FST) and tail suspension test (TST). To assess the possible involvement of NO, a non-specific NO synthase inhibitor, l-NAME (10?mg/kg, i.p.), and a specific iNOS inhibitor, aminoguanidine (AG) (50?mg/kg, i.p.), were administered separately 30?min before SM (20 and 100?mg/kg).

Results: SM at its effective doses 10, 20, 50, and 100?mg/kg decreased the immobility time in a dose-dependent manner (p?<?0.01, p?<?0.05, p?<?0.05, and p?<?0.001, respectively) in FST. SM (10, 20, 50, and 100?mg/kg) also lowered the immobility measure dose dependently in TST (p?<?0.01, p?<?0.05, p?<?0.01, and p?<?0.001, respectively). In addition, 50% of maximum response (ED₅₀) of SM was around 10?mg/kg. The dose 100?mg/kg proved the most effective dose in both the tests. Further, this effect was not related to changes in locomotor activity. Moreover, l-NAME reversed the effect of SM (20 and 100?mg/kg) in FST and SM (100?mg/kg) in TST. However, AG did not influence this impact.

Conclusion: The antidepressant-like effect of SM is probably mediated at least in part through NO and SM may increase NO tune.     

Protective effect of HMG CoA reductase inhibitors against running wheel activity induced fatigue,anxiety like behavior,oxidative stress and mitochondrial dysfunction in mice

BackgroundChronic fatigue stress (CFS) is an important health problem with unknown causes and unsatisfactory prevention strategies, often characterized by long-lasting and debilitating fatigue, myalgia, impairment of neuro-cognitive functions along with other common symptoms. The present study has been designed to explore the protective effect of statins against running wheel activity induced fatigue anxiety.MethodsMale albino Laca mice (20–30 g) were subjected to swim stress induced fatigue in a running wheel activity apparatus. Atorvastatin (10, 20 mg/kg, po) and fluvastatin (5, 10 mg/kg, po) were administered daily for 21 days, one hour prior to the animals being subjected to running wheel activity test session of 6 min. Various behavioral tests (running wheel activity, locomotor activity and elevated plus maze test), biochemical parameters (lipid peroxidation, nitrite concentration, glutathione levels and catalase activity) and mitochondrial complex enzyme dysfunctions (complex I, II, III and IV) were subsequently assessed.ResultsAnimals exposed to 6 min test session on running wheel for 21 days showed a significant decrease in number of wheel rotations per 6 min indicating fatigue stress like behavior. Treatment with atorvastatin (10 and 20 mg/kg) and fluvastatin (10 mg/kg) for 21 days significantly improved the behavioral alterations [increased number of wheel rotations and locomotor activity, and anxiety like behavior (decreased number of entries and time spent in open arm)], oxidative defence and mitochondrial complex enzyme activities in brain.ConclusionPresent study suggests the protective role of statins against chronic fatigue induced behavioral, biochemical and mito-chondrial dysfunctions.     

重组人源性锰超氧化物歧化酶对小鼠紫外线辐射所致氧化应激的保护作用

目的研究重组人源性锰超氧化物歧化酶(rhMn-SOD)对小鼠经A波紫外线(UV-A)辐射所致氧化应激损伤的保护作用。方法60只♂昆明种小鼠随机分为空白对照组、损伤模型组、天然铜锌超氧化物歧化酶(Cu,Zn-SOD)组及3个剂量rhMn-SOD给药组。每天于辐射前1 h给药,辐照时间4 h,连续9 d,d 10处死动物。检测肝、脑匀浆及红细胞(RBC)溶血液的丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)及总超氧化物歧化酶(SOD)。结果UV-A模型组的肝脑匀浆的3个抗氧化指标与空白对照组比较具差异有显著性意义(P<0.01),rhMn-SOD预防性给药组肝脏各指标与UV-A模型组相比差异均有显著性意义(P<0.05),并有剂量依赖性关系,但各组的红细胞指标差异均无显著性意义(P>0.05)。结论该UV-A辐射模型主要造成肝、脑氧化损伤,对红细胞无明显影响;rhMn-SOD对肝脏具有较好的保护作用。     

Possible GABAergic mechanism in the neuroprotective effect of gabapentin and lamotrigine against 3-nitropropionic acid induced neurotoxicity

Huntington's disease is a progressive neurodegenerative disorder that gradually reduces memory, cognitive skills and normal movements of affected individuals. Systemic administration of 3-Nitropropionic acid induces selective striatal lesions in rodents and non-human primates. Therefore, the present study has been designed to elucidate the comparative mechanistic profile of gabapentin, lamotrigine and their interactions with GABAergic modulators against 3-Nitropropionic acid induced neurotoxicity. Systemic 3-Nitropropionic acid (10 mg/kg) administration for 14 days significantly reduced body weight, locomotor activity, grip strength, oxidative defense (LPO, nitrite, SOD and catalase) and impaired mitochondrial complex enzyme (I, II, IV and MTT assay) activities in the striatum. 3-Nitropropionic acid treatment also increased TNF-α level in the striatum. Gabapentin (50 and 100 mg/kg) and lamotrigine (10, 20 and 40 mg/kg) treatments significantly restored behavioural, oxidative defense and mitochondrial complex enzyme activities and proinflammatory markers (TNF-α) as compared to 3-Nitropropionic acid treated group. Systemic picrotoxin (1 mg/kg) pretreatment with sub effective dose of gabapentin (50 mg/kg) or lamotrigine (20mg/kg) significantly attenuated their protective effect. Further, GABA (50 mg/kg) and/or muscimol (0.05 mg/kg) pretreatment with sub effective dose gabapentin (50 mg/kg) and lamotrigine (20 mg/kg) significantly potentiated their protective effects which were significant as compared to their effect alone. The results of the present study suggest that a GABAergic mechanism is involved in the protective effect of gabapentin and lamotrigine against 3-Nitropropionic acid induced neurotoxicity.     

Possible nitric oxide modulation in protective effect of FK-506 against 3-nitropropionic acid-induced behavioral,oxidative, neurochemical,and mitochondrial alterations in rat brain

FK-506 is an immunosuppressant being widely used for allograft rejection cases in the present clinical scenario. Recently, the neuroprotective effect of FK-506 has also been reported against a number of neurodegenerative diseases in rodents. This study was designed to explore the possible protective effect of FK-506 and its interaction with nitric-oxide modulators against 3-nitropropionic acid (3-NP)-induced behavioural, biochemical, neurochemical, and mitochondrial alterations in striatum, cortex, and hippocampus regions of the brain. Systemic administration of 3-nitropropionic acid produces Huntington-like symptoms in rats. 3-NP (10?mg/kg) treatment for 14 days impaired locomotor activity, grip strength, and body weight. 3-NP treatment significantly raised malondialdehyde, nitrite concentration, depleted antioxidant enzymes (SOD and catalase), and levels of bioamines (dopamine and norepinephrine) in striatum, cortex, and hippocampus areas of rat brain. Significant alterations in mitochondrial enzyme complexes (I, II, and IV) activities and mitochondrial redox activity have also been altered significantly by 3-NP. Pretreatment with FK-506 (0.5, 1, and 2?mg/kg) significantly reversed these behavioral, biochemical, and cellular alterations. L-arginine treatment with a subeffective dose FK-506 (1?mg/kg) reversed the protective effect of FK-506. However, L-NAME pretreatment with FK-506 (1?mg/kg) potentiated the protective effect of FK-506. The present study shows that FK-506 attenuates 3-NP-induced neurotoxicity and nitric-oxide modulation might be involved in its protective action.     

Involvement of glutamate, oxidative stress and inducible nitric oxide synthase in the convulsant activity of ciprofloxacin in mice

This study investigated the potential convulsive activity of ciprofloxacin in mice and the possible mechanism(s) of this activity. Intraperitoneal (i.p.) administration of ciprofloxacin into mice resulted in convulsive seizures in a dose-dependent manner. The clonic median convulsant dose (CD(50)) of ciprofloxacin in mice was increased by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine, not changed by pretreatment with 7-nitroindazole and decreased by pretreatment with L-arginine and fenbufen. The increase in nitric oxide (NO) production and malondialdehyde (MDA) level as well as the decrease in intracellular reduced glutathione (GSH) level and glutathione peroxidase (GSH-Px) activity induced by the estimated clonic CD(50) of ciprofloxacin in mice brain was inhibited by pretreatment with dizocilpine, alpha-lipoic acid or aminoguanidine. These biochemical alterations were not changed by pretreatment with 7-nitroindazole but enhanced by pretreatment with L-arginine. The elevation induced by the clonic CD(50) of ciprofloxacin in brain glutamate level was not changed by pretreatment with MK-801, alpha-lipoic acid, aminoguanidine or L-arginine. Combined treatment of mice with fenbufen and ciprofloxacin produced elevation of brain NO production and glutamate and MDA levels as well as inhibition of brain intracellular GSH level and GSH-Px activity. In addition, i.p. administration of the clonic CD(50) of ciprofloxacin produced an increase in inducible but not in neuronal NO synthase mRNA and protein expressions in mice brain. These results suggest that elevation of brain glutamate levels with consequent oxidative stress and increase in the expression and activity of brain inducible NO synthase may play a pivotal role in ciprofloxacin-induced convulsive seizures.     

Protective effect of betulinic acid against intracerebroventricular streptozotocin induced cognitive impairment and neuronal damage in rats: Possible neurotransmitters and neuroinflammatory mechanism

Background

The purpose of the study was to explore the therapeutic potential of Betulinic acid (BA) in streptozotocin (STZ) induced memory damage in experimental rats.

Oral administration of Cr(VI) induced oxidative stress, DNA damage and apoptotic cell death in mice

Potassium dichromate (Cr(VI)) was given orally to Swiss mice for 1 and 5 days with the dose of 25, 50 and 100 mg/kg body weight per day, respectively. Oxidative stress including the level of reactive oxygen species (ROS), the extent of lipid peroxidation and the activity of antioxidant enzymes in liver and kidney was determined. DNA damage in peripheral blood lymphocytes was determined by single-cell gel electrophoresis (comet assay). Apoptotic cell death in liver was detected using transmission electron microscopy and TUNEL assay. The results indicated that administration of Cr(VI) had caused a significant increase of ROS level in liver both after 1 and 5 days of exposure, accompanied with a dose-dependent decrease in superoxide dismutase (SOD) and catalase (CAT) activities. The malondialdehyde (MDA) content in liver was not changed as compared to the control animals. In contrast to the liver, no significant changes were observed in kidney on ROS, SOD, CAT and MDA as compared to the control animals. Dose- and time-dependent effects were observed on DNA damage after 1 and 5 days treatment. Significant difference was observed on the number of TUNEL positive liver cells between the control and Cr(VI) treatment groups. The apoptotic cells were also identified by characteristic ultrastructural features. The results obtained from the present study showed that Cr(VI) given orally to mice could induce dose- and time-dependent effects on DNA damage, hepatic oxidative stress and hepatocytes apoptosis. No significant oxidative stress observed in kidney in the study may suggest that the way of Cr(VI) exposure is an important factor affecting its toxicity.     

Neuroprotective effect of carvedilol, an adrenergic antagonist against colchicine induced cognitive impairment and oxidative damage in rat

Cognitive impairment and weak intellectual capacity is a gradually progressive neurodegenerative problem. Growing evidences indicate that oxidants and antioxidant defenses interact in a vicious cycle, which plays a critical role in the pathogenesis of cognitive dysfunction. The present study was carried out to elucidate the neuroprotective effect of carvedilol against the colchicine-induced cognitive impairment and oxidative damage in rats. Colchicine (15 µg/5 µl), a microtubule disrupting agent when administered intracerebroventricularly in rats resulted in poor memory retention in both Morris water maze, elevated plus maze task paradigms and caused marked oxidative stress as indicated by significant increase in malondialdehyde, nitrite levels, depletion of SOD, catalase, glutathione-S-transferase activity and reduced glutathione levels. It also caused a significant decrease in the acetylcholinesterase activity. Chronic administration of carvedilol (2.5 and 5.0 mg/kg; p.o.) for a period of 25 days, starting 4 days prior to colchicine administration resulted in an improvement in memory retention, attenuation of oxidative damage and restoration of acetylcholinesterase activity. Present study demonstrates a neuroprotective effect of carvedilol against colchicine-induced cognitive impairment and associated oxidative damage.     

Propofol, an anesthetic possessing neuroprotective action against oxidative stress, promotes the process of cell death induced by H2O2 in rat thymocytes

Propofol (2,6-diisopropylphenol) is a general anesthetic possessing a neuroprotective action against oxidative stress produced by H₂O₂. H₂O₂ induces an exposure of phosphatidylserine on outer surface of cell membranes, resulting in change in membrane phospholipid arrangement, in rat thymocytes. Since propofol is highly lipophilic, the agent is presumed to interact with membrane lipids and hence to modify the cell vulnerability to H₂O₂. Therefore, to test the possibility, we have examined the effect of propofol on rat thymocytes simultaneously incubated with H₂O₂. Although propofol (up to 30 μM) alone did not significantly affect the cell viability, the agent at 10 μM started to increase the population of dead cells in the presence of 3 mM H₂O₂ and the significant increase was observed at 30 μM. Propofol at clinically relevant concentrations (10–30 μM) facilitated the process of cell death induced by H₂O₂ in rat thymocytes. However, propofol protected rat brain neurons against the oxidative stress induced by H₂O₂ under same experimental condition. Therefore, the action of propofol may be dependent on the type of cells.     

Influence of nitric oxide agents in the dorsal hippocampus of mice on anxiogenic-like effect induced by histamine

Histaminergic receptors and neuronal nitric oxide synthase (nNOS) are co-expressed at high levels in the hippocampal neurons and alter anxiety-like behaviors in rodents. Since the dorsal hippocampus may be involved in modulation of anxiety-like behaviors, the aim of the present study was to assess whether the nitric oxide (NO) system in the dorsal hippocampus affects anxiety-like behaviors induced by histaminergic agents in mice. The effects of the NO precursor, L-arginine and NOS inhibitor, L-nitro-amino-methyl-ester (L-NAME) on histamine, pyrilamine and ranitidine responses in elevated plus maze (E.P.M.) in mice were investigated. Intra-CA1 microinjection of histamine (9 μg/mouse) or H1 receptor antagonist, pyrilamine (3, 6 and 9 μg/mouse), but not H2 receptor antagonist, ranitidine decreased the percentage of open arm time (%OAT) and open arm entries (%OAE), without affecting locomotor activity, suggesting an anxiogenic-like response. Both L-arginine (0.4 and 0.8 μg/mouse) and L-NAME (40 ng/mouse) when injected into the dorsal hippocampus induced anxiety-like behaviors, but the drugs reversed the anxiogenic response induced by the effective dose of histamine (9 μg/mouse) or pyrilamine (9 μg/mouse). Our results also indicated that intra-CA1 administration of L-arginine and L-NAME, in the presence or absence of ranitidine, exerted an anxiogenic effect. The results may indicate a modulatory role for NO in the dorsal hippocampus in the anxiogenic-like response induced by histamine or pyrilamine.     

Protective effect against brain tissues oxidative damage as a possible mechanism for beneficial effects of L-arginine on lipopolysaccharide induced memory impairment in rats

L-Arginine (LA) and nitric oxide (NO) have been suggested to have some effects on learning, memory, brain tissues oxidative damage, and neuroinflammation. In this study, protective effect against brain tissues oxidative damage as a possible mechanism for beneficial effects of LA on lipopolysaccharide (LPS) induced memory impairment was investigated. The rats were grouped into and treated by (1) control (saline), (2) LPS (1?mg/kg, IP), (3) LA (200?mg/kg) – LPS (4) LA. In passive avoidance (PA) test, LPS administration shortened the latency to enter the dark compartment in LPS group compared to control (p?p?p?p?p?p?p?p?p?p?p?相似文献   

Inducible nitric oxide synthase is not essential for the development of fibrosis and liver damage induced by CCl4 in mice

The aim of the present work was to investigate the role of inducible nitric oxide (NO) synthase (iNOS) in CCl(4)-induced cirrhosis by utilizing iNOS knock out mice (iNOS(-/-)). Cirrhosis was produced by i.p. administration of CCl(4) (1 ml kg(-1) of body weight) dissolved in olive oil three times a week for 3 months to iNOS(-/-) or iNOS(+/+) (wild type) mice; appropriate olive oil controls were performed. Nitrite plus nitrate levels were lower in iNOS(-/-) compared with iNOS(+/+) mice, but CCl(4) did not produce a significant effect in any mice. Reduced (GSH) glutathione was increased in iNOS(-/-) mice receiving vehicle and in both groups receiving CCl(4); lipid peroxidation increased significantly in iNOS(+/+) but not in iNOS(-/-) mice. Bilirubins, alanine aminotransferase and collagen (measured as the hepatic hydroxyproline content) were increased significantly by the chronic intoxication with CCl(4) in both iNOS(-/-) and iNOS(+/+) mice; importantly there was no difference between these groups. This study clearly suggests that NO derived from iNOS does not participate in cholestasis, necrosis or fibrosis induced by CCl(4) in the mice. The present results are in disagreement with several studies indicating a beneficial or detrimental effect of this molecule utilizing different experimental approaches and in agreement with some studies indicating that NO does not affect liver damage in some models. It must be pointed out that this is the first report in iNOS knock out mice utilizing the chronic model of intoxication with CCl(4); thus, comparisons with other models or approaches are difficult to reconcile.     

Protective effect of Vitamin D3 against lead induced hepatotoxicity,oxidative stress,immunosuppressive and calcium homeostasis disorders in rat

Lead (Pb) is an extremely poisonous, non-essential trace element and toxicity develops in humans following frequent exposure to the heavy metal in polluted environmental and occupational settings. Pb induces hepatic damage through the depletion of the antioxidant system, enhancing cellular oxidative stress and stimulation of proinflammatory cytokines. Although the antioxidant and anti-inflammatory actions of vitamin D₃ (VD₃) are well-established, a minority of studies measured the protective actions of VD₃ against Pb toxicity. Therefore, this work studied the effects of vitamin VD₃ therapy on the fundamental molecular basis underlying hepatic injury induced by chronic Pb toxicity. Twenty-four adult male rats were distributed equally into the negative controls (NC), positive controls (PC) and VD3 groups. While both the PC and VD3 groups received Pb-acetate in drinking water (1000 mg/L) for four weeks, the latter group also received intramuscular VD3 injections (1000 IU/kg; 3 days/week) simultaneously with Pb. The liver enzymes together with the serum and hepatic tissue Pb concentrations increased markedly in the PC group compared with the NC group. Pb toxicity also drastically induced hepatocyte apoptosis/necrosis, increased the hepatic tissue concentrations of malondialdehyde and the pro-inflammatory cytokines (TGF-β, IL-4 & TNF-α) as well as reduced the anti-oxidative enzymes (GSH, GPx & CAT) and the anti-inflammatory cytokine, IL-10, compared with the NC group. Pb also significantly decreased the serum concentrations of VD3 and Ca²⁺. Additionally, the hepatic expressions of VD receptor, Cyp24a1 enzyme, L-type Ca²⁺-channel, calbindin-D_28k & -D_29k, calmodulin and calmodulin-dependent protein kinase II were significantly upregulated, whereas the VD binding protein, CYP2R1 enzyme and T-type Ca²⁺-channel were markedly inhibited at the gene and protein levels following Pb intoxication. VD3 alleviated the hepatic damage, inhibited the oxidative stress and pro-inflammatory molecules as well as upregulated the anti-oxidant and anti-inflammatory markers and restored the expression of the VD/Ca²+ regulatory molecules compared with the PC group. VD3 supplementation discloses promising protective effects against Pb-induced hepatic damage, through its anti-inflammatory and antioxidant actions as well as by modulating the hepatocyte calcium homeostatic molecules.     

DNA damage and oxidative stress induced by CeO2 nanoparticles in human dermal fibroblasts: Evidence of a clastogenic effect as a mechanism of genotoxicity

Abstract

The broad range of applications of cerium oxide (CeO₂) nanoparticles (nano-CeO₂) has attracted industrial interest, resulting in greater exposures to humans and environmental systems in the coming years. Their health effects and potential biological impacts need to be determined for risk assessment. The aims of this study were to gain insights into the molecular mechanisms underlying the genotoxic effects of nano-CeO₂ in relation with their physicochemical properties. Primary human dermal fibroblasts were exposed to environmentally relevant doses of nano-CeO₂ (mean diameter, 7?nm; dose range, 6?×?10^?5–6?×?10^?3?g/l corresponding to a concentration range of 0.22–22?µM) and DNA damages at the chromosome level were evaluated by genetic toxicology tests and compared to that induced in cells exposed to micro-CeO₂ particles (mean diameter, 320?nm) under the same conditions. For this purpose, cytokinesis-blocked micronucleus assay in association with immunofluorescence staining of centromere protein A in micronuclei were used to distinguish between induction of structural or numerical chromosome changes (i.e. clastogenicity or aneuploidy). The results provide the first evidence of a genotoxic effect of nano-CeO₂, (while not significant with micro-CeO₂) by a clastogenic mechanism. The implication of oxidative mechanisms in this genotoxic effect was investigated by (i) assessing the impact of catalase, a hydrogen peroxide inhibitor, and (ii) by measuring lipid peroxidation and glutathione status and their reversal by application of N-acetylcysteine, a precusor of glutathione synthesis in cells. The data are consistent with the implication of free radical-related mechanisms in the nano-CeO₂-induced clastogenic effect, that can be modulated by inhibition of cellular hydrogen peroxide release.     

Role of oxidative stress and nitric oxide in the protective effects of α-lipoic acid and aminoguanidine against isoniazid–rifampicin-induced hepatotoxicity in rats

Despite the great efficacy of isoniazid (INH) and rifampicin (RIF) combination, in the treatment of tuberculosis, hepatotoxicity is the most common serious complication. The potential protective effect of α-lipoic acid and aminoguanidine; against combination-induced hepatotoxicity was investigated in the present study. Administration of INH–RIF combination (50 mg/kg each for 14 days) resulted in an elevation of serum hepatic marker enzymes and a significant increase in lipid profile parameters. Combinations treatment increased lipid peroxidation products, decreased glutathione content, superoxide dismutase, catalase and myeloperoxidase activities. Furthermore, liver total nitrite level was significantly increased in INH–RIF treated rats. Co-administration of either α-lipoic acid or aminoguanidine significantly ameliorate combination-induced alterations in hepatic marker enzymes. These effects were directly linked to a greater decrease in the combination-induced elevation in lipid peroxidation products and total nitrite levels. Furthermore, co-administration of α-lipoic acid and aminoguanidine restore superoxide dismutase, catalase and myeloperoxidase activities and maintained the imbalance in the glutathione level. Additionally, such beneficial effect of α-lipoic acid was linked to a marked lipid-lowering effect. Histopathological examination revealed preservation of liver integrity of the protected groups compared to combination-treated rats alone.     

Neuroprotective effect of Manasamitra vatakam against aluminium induced cognitive impairment and oxidative damage in the cortex and hippocampus of rat brain

Manasamitra vatakam (MMV) has long been used as a traditional medicine in India for the treatment of psychosomatic diseases, anxiety neurosis, and stress. The present study was designed to examine the neuroprotective effect of MMV against aluminum (Al)-induced memory impairment and oxidative damage in rats. Neurotoxicity was induced by the administration of Al [100?mg/kg body weight (b.w.) per oral (p.o.)/day] to Wistar albino rats for 90 days. Al administration induced neurotoxicity as well as oxidative stress by affecting the active avoidance and memory impairment, as well as altering antioxidants, such as HSP70 protein, superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase, and acetylcholinesterase. It was observed that the administration of MMV (100?mg/kg b.w./p.o./day) along with AlCl₃ improves memory performance and antioxidant activity against Al-induced neurotoxicity in rats. In conclusion, these data suggest that MMV can prevent brain damage from Al-induced neurotoxicity in rats and thus can be used as a neuroprotective agent.     

Protective effect of vineatrol against kainic acid induced seizures, oxidative stress and on the expression of heat shock proteins in rats.

The aim of the present study was to evaluate the effect of an antioxidant vineatrol against kainic acid-induced seizures, markers of oxidative stress and expression of heat shock protein in brain. In rats, kainic acid (10 mg/kg i.p.) induced long lasting seizures, associated behavioral symptoms and brain damage and significantly increased level of brain malondialdehyde (MDA) (283 +/- 42 nmol/g wet tissue) as compared to control (173.3 +/- 10.2 nmol/g wet tissue). Pretreatment (5 min) of vineatrol (10, 20 and 40 mg/kg i.p.) could not inhibit the convulsions though the latency was significantly increased with 20 and 40 mg/kg. However when the drug was administrated 5 min prior and repeated at 30 and 90 min after kainic acid there was significant reduction in incidence of convulsions. The brain MDA levels were also found to be significantly attenuated, however the glutathione levels were not different in control, kainic acid and vineatrol treated animals. Expression of heat shock protein (HSP) 72 was observed in the kainic acid per se group indicating neurotoxicity as compared to the control group and was reduced by vineatrol. The study suggests the potential use of vineatrol in status epilepticus.     

Ameliorative effect of lithium chloride against d-galactose induced behavioral and memory impairment,oxidative stress and alteration in serotonin function in rats

BackgroundAging is a phenomenon that all living organisms surely face. d-galactose (D-gal) has been used to develop an aging model of brain. Lithium (Li) has been proposed to have neuroprotective properties in relation to several neurological disorders. The goal of the current studyis to evaluate the effect of Lithium Chloride (LiCl) on D-gal induced neurological disorders and oxidative stress.MethodsRats were treated with D-gal at a dose of 300 mg/ml/kg and various doses of LiCl (20, 40 and 80 mg/ml/kg) for 14 days. After that behavioral analysis (Elevated plus maze (EPM); Light dark box test (LDT); Morris water maze (MWM); Forced swim test (FST)) were performed. Animals were decapitated after behavioral tests and brain samples were collected for biochemical (malondialdehyde (MDA); superoxide dismutase (SOD); catalase (CAT); glutathione peroxidase (GPx); acetylcholiesterase (AChE)) and neurochemical analysis (5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA)).ResultsThe results showed that administration of LiCl at all doses ameliorates D-gal induced, decreased time spent in the open arm and light box in EPM and LDT respectively, increased immobility in FST, increased latency escape in MWM, increased MDA levels, decreased antioxidant enzyme, increased AChE activity and decreased 5-HT metabolism.ConclusionsIn conclusion, the present study indicated that D-gal induced anxiety/depression like symptoms and memory impairment were ameliorated by LiCl (at all doses) possibly via its antioxidant effects and normalizing 5-HT function.     

Protective effect of taurine against potassium bromate‐induced hemoglobin oxidation,oxidative stress,and impairment of antioxidant defense system in blood

Potassium bromate (KBrO₃) is widely used as a food‐additive and is a major water disinfection by‐product. KBrO₃ causes severe toxicity in humans and experimental animals. Bromate is considered a probable human carcinogen and a complete carcinogen in animals. We have investigated the potential role of taurine in protecting against KBrO₃‐induced oxidative stress in rat blood. Animals were given taurine for 5 days prior to KBrO₃ and then sacrificed. Blood was collected and used to prepare hemolysates and plasma, which were then used for the analysis of several biochemical parameters. Administration of single oral dose of KBrO₃ alone induced hepato‐ and nephro‐toxicity as evident by elevated marker levels in plasma. Lipid peroxidation and protein oxidation were increased both in plasma and erythrocytes, suggesting the induction of oxidative stress. KBrO₃ increased methemoglobin, nitric oxide, and hydrogen peroxide levels. It also altered the activities of the major antioxidant enzymes and lowered the antioxidant power of blood. Administration of taurine, prior to treatment with KBrO₃, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. These results show that taurine is effective in mitigating the oxidative insult induced in rat blood by KBrO₃. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 304–313, 2016.