Attenuation of oxidative stress and neurotoxicity involved in the antidepressant-like effect of the MK-801(dizocilpine) in Bacillus Calmette-Guerin-induced depression in mice.

Background The emerging line of research suggests that neuro-inflammation and oxidative stress are linked to the development of depression-like behavior. The tryptophan metabolizing enzyme, indolamine 2,3-dioxygenase (IDO), serves as an important interface between chronic inflammation and depression. IDO is induced by pro-inflammatory cytokines and diverts tryptophan towards the kynurenine pathway, decreasing serotonin synthesis. Further, the metabolites of kynurenine pathway increase brain oxidative stress and also cause N-methyl-D-aspartate (NMDA) receptor-mediated exitotoxicity. The resulting oxidative damage and dysfunction in glutamatergic neurotransmission alters the network connectivity of the brain, which may be the further mechanism for emergence of depression-like symptoms. Methods A depression-like illness was induced in mice by injecting Bacillus Calmette-Guerin (BCG) suspended in isotonic saline at a dose of 107 CFU I.P. The mice were then divided into different groups and were administered MK-801 or normal saline for the next 21 days, after which a battery of behavior and biochemical tests were conducted to assess them. Results The BCG group had significantly reduced sucrose preference index and an increase in immobility time in forced swim test (FST) and Tail Suspension Test (TST) as compared to the saline group. There was also a significant increase in the brain MDA levels and a decline in the brain GSH levels. The hippocampal tissue from the BCG group had significantly more comet cells than the saline group. The NMDA receptor antagonist, MK-801, was able to reverse the BCG-induced depression-like behaviour. MK-801 also showed significant decrease in brain oxidative stress but failed to show significant protection against BCG-induced neurotoxicity observed in comet assay. Conclusions The NMDA receptor antagonist, MK-801, mitigated BCG-induced, depressive-like behavior in mice by improving the sucrose preference and decreasing the duration of immobility time in TST and FST. The overall improvement in depression-like behavior was accompanied by a reduction in brain oxidative stress and comet cells, thus suggesting the antioxidant and neuroprotective action of MK-801.

Cadmium level in brain correlates with memory impairment in F1 and F2 generation mice: improvement with quercetin.

The increased exposure to cadmium (Cd) through environmental pollutants, food and cigarette smoke is a concern worldwide. The association of Cd with impaired learning disabilities led us to hypothesise that cadmium levels in brain tissue could be dose-dependently related to the extent of memory impairment and oxidative stress. In this study, we proposed to study whether cadmium exposure to dams could alter the brain Cd levels, memory parameters, antioxidant enzymes in brain and their gene expression in the F1-F2 generation mice and whether quercetin could modulate this effect. Animals were administered Cd alone and in combination with quercetin for 7 days during their gestation period. Their newborn pups (F1 and F2 mice) were reared until adulthood and were tested for memory using Morris water maze and step-down latency test. The brain tissue of F1 mice was collected. Cd levels were estimated using the atomic absorption spectrophotometer. G-S-transferase (GST) and catalase (CAT) activity were measured and fold increase in their respective gene expression was observed using the RT-PCR method. Cd levels were significantly increased in the brain tissue of animals exposed to Cd but cotreatment with quercetin showed decreased levels in both generations. Memory impairment was observed in animals of F1 generation exposed to Cd and cotreatment with quercetin (100 mg/kg) reversed this effect. Cd exposure significantly enhanced both activity and expression of GST and CAT in the brain tissue of F1 generation mice and quercetin attenuated this effect. In F2 generation, results were variable. GST activity and expression increased with Cd and decreased with quercetin cotreatment. However, CAT activity showed no significant change despite a decrease in gene expression. Quercetin cotreatment enhanced activity as well gene expression in F2 generation. Our study insinuates that Cd levels could act as a predictor of memory impairment and altered enzyme activity and gene expression in brain tissue. Quercetin helped to reduce Cd levels in brain tissue of F1 and F2 generation and modulated the antioxidant system of the cell by affecting expression of antioxidant enzymes at the transcription level.

Alteration in cognitive behaviour, brain antioxidant enzyme activity and their gene expression in F1 generation mice, following Cd exposure during the late gestation period: modulation by quercetin.

We investigated whether in-utero Cd(II) chloride exposure of the dams between 14th to 21st day of gestation affects memory and learning, oxidative stress, antioxidant enzyme activity and their gene expression in brain of the pups in their adulthood. In the Morris water maze, cadmium (Cd) exposure impaired spatial memory which was reversed following co-treatment with quercetin (100 mg/kg). In the passive avoidance paradigm, retention memory was adversely affected but was significantly reversed by co treatment with quercetin (25, 50, 100 mg/kg). The malondialdehyde and catalase (CAT) levels and glutathione-S-transferase (GST) activity were increased significantly in Cd-treated group, but were reversed by quercetin (all doses). The gene expression for CAT and GST in brain tissue of Cd treated animals also increased many folds as compared to the control, and this effect was decreased on co-treatment with quercetin (all doses), thus matching with the respective enzyme activities. Quercetin (25 mg/kg) when co-treated with Cd caused a decrease in GST activity compared to control, which points towards a complex interplay with oxidative free radicals and promoters and transcription factors. Thus, Cd exposure during late gestation causes impaired spatial and retention memory in the next generation which may be due to alteration of activity as well as gene expression of the antioxidant enzymes, CAT and GST. Quercetin may offer some protection of memory impairment probably by modulating these effects.

Anticonvulsant and Antioxidant Effects of Musa sapientum Stem Extract on Acute and Chronic Experimental Models of Epilepsy.

BACKGROUND: Musa sapientum (banana) plant extract has been shown to possess antioxidant activity in previous studies. Neuronal injury resulting from oxidative stress is an important factor involved in pathogenesis of epilepsy. OBJECTIVE: The present study aimed to evaluate the anticonvulsant activity of M. sapientum stem extract (MSSE) in acute and chronic experimental models in mice and its effects on various markers of oxidative stress in the brain of pentylenetetrazole (PTZ)-kindled animals. MATERIAL AND METHODS: Maximal electroshock seizures (MES) and PTZ-induced convulsion models were used for acute studies. For the chronic study, the effect of MSSE on the development of kindling was studied. For the evaluation of the effects of MSSE on oxidative stress in brain, malondialdehyde (MDA) and reduced glutathione (GSH) levels were estimated in the brains of the kindled animals. RESULTS: MSSE significantly increased the latency to onset of myoclonic jerks and the duration of clonic convulsions following PTZ administration. The MSSE pretreated group showed significantly reduced mean seizure score on PTZ-induced kindling. There was a significant increase in the brain MDA levels and decrease in GSH levels in response to PTZ-induced kindling. On MSSE pretreatment, there was a significant decrease in the MDA levels in the brains, though the increase in the GSH levels was not significant. CONCLUSION: The results from this study suggest the presence of significant anticonvulsant activity in MSSE, in both acute and chronic PTZ-induced seizure models, which could be due to its antioxidant activity, as is reflected by the change in oxidative stress markers in brain. SUMMARY: Evaluation of the anticonvulsant activity of Musa sapientum and its effects on various markers of oxidative stress in the brain has not been done previously to the best of our knowledgeM. sapientum stem extract (MSSE) significantly increased the latency to onset of myoclonic jerks and the duration of clonic convulsions in the experimental modelsThe MSSE pretreated group showed significantly reduced mean seizure score on pentylenetetrazole (PTZ)-induced kindlingThere was significant increase in the brain malondialdehyde (MDA) levels and decrease in glutathione (GSH) levels in response to PTZ-induced kindlingOn MSSE pretreatment, there was a significant decrease in the MDA levels in the brain, though the increase in the GSH levels was not significant. Abbreviations Used: MSSE: Musa sapientum stem extract, PTZ: Pentylenetetrazole, MES: Maximal electroshock seizures, MDA: Malondialdehyde, GSH: Glutathione, SOD: Superoxide dismutase, THLE: Tonic hindlimb extension.

Anti-anxiety and Anti-depressant Like Effects of Murraya koenigii in Experimental Models of Anxiety and Depression.

BACKGROUND: Presence of free radical scavenging activity in Murrayakoenigii, commonly known as Curry leaves, has been shown in previous studies. Oxidative stress plays an important role in the development of various neurobehavioral disorders including anxiety and depression. AIM: The present study aimed to evaluate the effects of Murraya koenigii in animal models of depression and anxiety. MATERIALS AND METHODS: The effect of incremental doses of Murraya koenigii aqueous leaf extract was evaluated on spontaneous motor activity (SMA), open arm incursions in elevated plus maze, and despair behaviour in forced swim (FST) and tail suspension (TST) tests as compared to control groups in Swiss albino mice. RESULTS: Murraya koenigii 300 mg/kg, p.o. (MK300) and 400 mg/kg, p.o. (MK400) reduced the SMA count from 754 ± 64.9 to 540 ± 29 and 295 ± 34 respectively, which was statistically significant. MK300 and MK400 reduced significantly the open arm count from 29 ± 8.6 to 16 ± 7 and 10 ± 3.9, respectively. On FST, MK400 reduced the duration of immobility from 145.5 ± 29 to 91 ± 17.3, which was statistically significant. On TST, MK produced a dose-dependent decrease in the duration of immobility; however, it was statistically significant only with MK400. CONCLUSION: Murraya koenigii aqueous leaf extract reduced the despair behavior in experimental animal models, suggesting an anti-depressant like activity. Murraya koenigii extract also reduced spontaneous locomotor activity in a dose-dependent manner suggesting a sedative and/or anxiolytic effect though there wasn't any anxiolytic effect in the elevated plus maze test.

Effects of Musa sapientum stem extract on experimental models of anxiety.

OBJECTIVE: The Musa sapientum (banana) plant extract has shown antioxidant activity in previous studies. Oxidative stress is one of the important factors implicated in the pathogenesis of anxiety disorders. The present study aimed to evaluate the anxiolytic activity of aqueous extract of M. sapientum stem (MSSE) in experimental models in mice. MATERIAL AND METHODS: Elevated Plus Maze method and locomotor monitoring by photoactometer were used. Animals were divided into five different groups (n=6/group). The vehicle, standard and the experimental groups were given distilled water (10 ml/kg), diazepam (1 mg /kg intraperitoneally) and incremental doses of 25, 50 and 100 mg/kg of MSSE, respectively, prior to the experiment. The standard group received diazepam. RESULTS: The number of open arm entries and the duration of time spent in the open arms in the MSSE-treated groups increased significantly in a dose-dependent manner as compared to that of control group. The duration of time spent in closed arms in the MSSE-treated groups decreased significantly in a dose-dependent manner as compared to that of the control group. MSSE also decreased the locomotor activity significantly at all three test doses. CONCLUSION: The results of this study suggest an anxiolytic activity for MSSE, which make it a potential natural compound for treatment of anxiety disorders.

Effect of Musa sapientum Stem Extract on Animal Models of Depression.

BACKGROUND: Musa sapientum, the banana plant, has shown to possess antioxidant activity in previous studies. Oxidative stress has been linked to the pathogenesis of major depressive disorder (MDD) with evidence of increased serum levels of oxidative stress biomarkers in MDD patients. OBJECTIVE: The present study aimed to evaluate the antidepressant activity of M. sapientum stem extract (MSSE) in experimental models in mice. MATERIALS AND METHODS: Forced swim test (FST) and tail suspension test (TST) were carried out in five different groups (n = 6/group) of mice. The vehicle, standard drug, and the three test groups were orally administered distilled water (10 mL/kg), fluoxetine (25 mg/kg), and incremental doses of 25, 50, and 100 mg of MSSE, respectively, 45 min prior to the experiment. RESULTS: On FST, the duration of immobility in control group, which was 161.5 ± 6.78 (in seconds, mean ± standard error of mean [SEM]), decreased to 149.33 ± 2.70 (25 mg/kg MSSE), 120.17 ± 8.35 (50 mg/kg MSSE), and 45.17 ± 4.11 (100 mg/kg MSSE) in the treated groups. On TST, the duration of immobility in control group, which was 173.83 ± 12.65 (mean ± SEM), decreased to 163.17 ± 6.91 (25 mg/kg MSSE), 139.0 ± 5.9 (50 mg/kg MSSE), and 124.0 ± 4.42 (100 mg/kg MSSE) in the treated groups. The difference in the duration of immobility was statistically significant at middle and higher doses, i.e. 50 and 100 mg/kg MSSE (P < 0.05) respectively, when compared with the control group in both the tests. CONCLUSION: A significant antidepressant-like activity was found in MSSE, which could be a potential natural compound for use in depression. SUMMARY: The five groups - vehicle, standard drug, and the three test groups were administered distilled water (10 mL/kg), fluoxetine (25 mg/kg), and incremental doses of 25, 50, and 100 mg of Musa sapientum stem extract (MSSE), respectivelyThe duration of immobility decreased in the treated groups as compared to the control group on both, forced swim and tail suspension, testsThe difference in the duration of immobility was statistically significant at middle and higher doses, i.e., 50 and 100 mg/kg MSSE (P < 0.05), when compared with the control group in both the tests. Abbreviations Used: MDD: Major depressive disorder; MSSE: Musa sapientum stem extract; FST: Forced swim test; TST: Tail suspension test; GSH: Glutathione, MDA: Malondialdehyde; SOD: Superoxide dismutase.

Comparison of fluoxetine and 1-methyl-L-tryptophan in treatment of depression-like illness in Bacillus Calmette-Guerin-induced inflammatory model of depression in mice.

BACKGROUND: The inflammatory response system has been implicated in the pathophysiology of major depression. The pro-inflammatory cytokines like interferon-γ induce the enzyme indoleamine-2,3-dioxygenase (IDO) of the kynurenine pathway of tryptophan metabolism. The induction of IDO reduces the availability of tryptophan for serotonin synthesis. Furthermore, the metabolites of kynurenine pathway have neurotoxic property, which along with decreased serotonin may account for depression-like illness. METHODS: The aim of this study was to compare the effects of treatment with fluoxetine and 1-methyl-L-tryptophan (1-MT) on Bacillus Calmette-Guerin (BCG)-induced inflammatory model of depression in mice. Behavioral tests included locomotor activity, forced swim test (FST) and tail suspension test (TST). Oxidative stress was assessed by examining the levels of thiobarbituric acid reactive species (TBARS) and non-protein thiols (NP-SH) in homogenized whole brain samples. Comet assays were performed to assess neurotoxicity. RESULTS: The results of this study demonstrate that BCG treatment resulted in an increase in duration of immobility in FST and TST as compared to the saline group. Further, it produced a significant increase in the brain TBARS levels and decrease in the brain NP-SH levels. The hippocampal tissue from BCG group had significantly more comet cells than the saline group. 1-MT and fluoxetine were able to reverse the BCG-induced depression-like behavior and the derangement in oxidative stress parameters. Fluoxetine and 1-MT also reversed the BCG-induced neurotoxicity in such mice. CONCLUSIONS: 1-Methyl-L-tryptophan exhibits antidepressant-like effect comparable to that of fluoxetine in treating BCG-induced depression-like behavior in mice.

Effect of Low Level Subchronic Microwave Radiation on Rat Brain.

OBJECTIVE: The present study was designed to investigate the effects of subchronic low level microwave radiation (MWR) on cognitive function, heat shock protein 70 (HSP70) level and DNA damage in brain of Fischer rats. METHODS: Experiments were performed on male Fischer rats exposed to microwave radiation for 90 days at three different frequencies: 900, 1800, and 2450 MHz. Animals were divided into 4 groups: Group I: Sham exposed, Group II: animals exposed to microwave radiation at 900 MHz and specific absorption rate (SAR) 5.953 × 10-4 W/kg, Group III: animals exposed to 1800 MHz at SAR 5.835 × 10-4 W/kg and Group IV: animals exposed to 2450 MHz at SAR 6.672 × 10-4 W/kg. All the animals were tested for cognitive function using elevated plus maze and Morris water maze at the end of the exposure period and subsequently sacrificed to collect brain tissues. HSP70 levels were estimated by ELISA and DNA damage was assessed using alkaline comet assay. RESULTS: Microwave exposure at 900-2450 MHz with SAR values as mentioned above lead to decline in cognitive function, increase in HSP70 level and DNA damage in brain. CONCLUSION: The results of the present study suggest that low level microwave exposure at frequencies 900, 1800, and 2450 MHz may lead to hazardous effects on brain.

Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin.

Cadmium (Cd) is a known pollutant present in the environment at low levels and is reported to affect reproduction in many ways. The present study was undertaken to explore the effect of Cd in F1 generation mice on cognitive parameters, and to further investigate whether quercetin could modulate these effects. In this study, female lactating mice were exposed to cadmium for seven days just after delivery. The new born pups in their adulthood were tested for learning and memory parameters by passive avoidance task and Morris water maze (MWM) test. It was observed that pups exposed to Cd showed significant impairment of memory in step down latency test, which was reversed by quercetin (100 mg/kg). In MWM test for spatial memory, animals exposed to Cd exhibited increased escape latency, which was reversed by quercetin (50 mg/kg) significantly. Quercetin alone (50 and 100 mg/kg) also demonstrated improved spatial memory, and showed improved retention memory in the passive avoidance paradigm at dose 50 mg/kg. On testing oxidative stress parameters, we observed significantly increased malondialdehyde (MDA) levels in brain tissue of Cd-treated mice. Moreover, co-treatment with quercetin (50 mg/kg) and Cd significantly reduced these MDA levels. The other doses (25 and 100 mg/kg) also showed reduction in MDA levels as compared to the group exposed to Cd alone, though the difference was not statistically significant. Hence, this study highlights the possibility of cognitive impairment in adulthood if there is Cd exposure during lactation and oxidative stress could possibly attribute to this effect.

Quercetin Modulates the Effects of Chromium Exposure on Learning, Memory and Antioxidant Enzyme Activity in F1 Generation Mice.

In the present study, we investigated whether chromium (Cr) administered to the dams (F0) during lactation period could affect memory and oxidative stress in F1 generation mice in their adulthood and whether quercetin could modulate these effects. Morris water maze (MWM) was used to test for spatial memory. Passive avoidance task and elevated plus maze were used to test for acquisition and retention memory. Oxidative stress was evaluated by measuring glutathione-S-transferase (GST), catalase activity and malonaldehyde (MDA) levels in the brain tissue. The results of MWM showed that the animals in the Cr-treated group compared to control have better spatial memory that was further enhanced when Cr was administered along with quercetin (50 mg/kg). The elevated plus maze test also showed the Cr-treated group to improve acquisition as well as retention memory compared to control. Co-treatment with quercetin (all doses) also exhibited enhanced acquisition and retention memory compared to control. The passive avoidance task demonstrated no significant improvement in memory in the Cr-treated mice but co-treatment with quercetin (100 mg/kg) showed improved acquisition memory compared to control which was significantly better than the animals treated with chromium alone. GST activity was significantly increased in the Cr-treated animals, and this was further increased in groups treated with Cr and quercetin (all doses). Chromium when administered alone and in combination with quercetin (all doses) significantly reduced MDA levels. However, Cr treatment did not show significant change in catalase activity. Nevertheless, co-treatment with quercetin (25 and 50 mg/kg) resulted in significant decrease in catalase activity. Thus, our study demonstrates that Cr exposure during lactation could be beneficial for pups with respect to augmentation of cognitive function and reduction of oxidative stress. Quercetin could probably enhance this effect to some extent.

CYP2D6*2 Polymorphism as a Predictor of Failed Outpatient Tramadol Therapy in Postherpetic Neuralgia Patients.

Human cytochrome P4502D6 (CYP2D6) gene is highly polymorphic, leading to wide interindividual ethnic differences in CYP2D6-mediated drug metabolism. Its activity ranges from complete deficiency to excessive activity, potentially causing toxicity of the medication or therapeutic failure with recommended drug dosages. The aim of the study was to find the association of CYP2D6*2 polymorphisms with demographic characters (age, sex, and weight), pain intensity scales [numerical rating scale (NRS) sleep, global perceived effect (GPE)], and adverse drug effects in postherpetic neuralgia (PHN) patients receiving tramadol. The study comprised 246 patients [including 123 nonresponders (NRs) and 123 responders (Rs)] with PHN undergoing analgesic treatment at the pain clinic, Out Patient Department, University College of Medical Sciences, Guru Teg Bahadur Hospital, Delhi, India. Patients with any history of diabetes mellitus, human immunodeficiency virus, malignancy, hematological or liver disease, psychiatric illness, alcohol abuse, and tramadol sensitivity were excluded from the study. The NRSs of (resting and movement), NRS-sleep, and GPE were evaluated by the treating physician. Adverse drug effects during the time of the study were recorded. All samples were analyzed for CYP2D6*2 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism method. The genotype distribution did not vary significantly among genders [NR (P = 0.723); R (P = 0.947)] and different age groups in NRs (P = 0.763) and Rs (P = 0.268). Clinically, statistically significant (P < 0.001) results were obtained in both the groups when compared with baseline in the NRS-sleep and GPE scores, whereas no association was found between NRS-sleep and GPE scores when compared with CYP2D6*2 genotype (P > 0.05). In addition, CYP2D6*2 genotype was not related to the adverse effects of analgesic therapy. The overall results suggested that CYP2D6*2 polymorphism plays no role in the PHN patients receiving tramadol treatment. The CYP2D6*2 polymorphism may not be a predictor of treatment outcome of patients with respect to PHN-receiving tramadol.

Suvorexant: The first orexin receptor antagonist to treat insomnia.

Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, have often been associated with adverse effects, such as, day-time somnolence, amnesia, confusion, and gait disturbance, apart from the risk of dependence on chronic use. Suvorexant has not shown these adverse effects because of its unique mechanism of action. It also appears to be suitable as a chronic therapy for insomnia, because of minimal physical dependence. The availability of this new drug as an effective and safe alternative is an important and welcome development in insomnia management.

Cognitive impairment and neurogenotoxic effects in rats exposed to low-intensity microwave radiation.

The health hazard of microwave radiation (MWR) has become a recent subject of interest as a result of the enormous increase in mobile phone usage. The present study aimed to investigate the effects of chronic low-intensity microwave exposure on cognitive function, heat shock protein 70 (HSP70), and DNA damage in rat brain. Experiments were performed on male Fischer rats exposed to MWR for 180 days at 3 different frequencies, namely, 900, 1800 MHz, and 2450 MHz. Animals were divided into 4 groups: group I: sham exposed; group II: exposed to MWR at 900 MHz, specific absorption rate (SAR) 5.953 × 10(-4) W/kg; group III: exposed to 1800 MHz, SAR 5.835 × 10(-4) W/kg; and group IV: exposed to 2450 MHz, SAR 6.672 × 10(-4) W/kg. All the rats were tested for cognitive function at the end of the exposure period and were subsequently sacrificed to collect brain. Level of HSP70 was estimated by enzyme-linked immunotarget assay and DNA damage was assessed using alkaline comet assay in all the groups. The results showed declined cognitive function, elevated HSP70 level, and DNA damage in the brain of microwave-exposed animals. The results indicated that, chronic low-intensity microwave exposure in the frequency range of 900 to 2450 MHz may cause hazardous effects on the brain.

Effect of Cinnamomum zeylanicum extract on scopolamine-induced cognitive impairment and oxidative stress in rats.

OBJECTIVE: Cinnamomum zeylanicum (CZ) is commonly known as cinnamon in traditional system of medicine having antibacterial, antioxidant, antidiabetic, hypolipidemic, and other activities. The present study was designed to assess the effect of extract of CZ bark on cognitive performance of scopolamine (SCOP)-treated rats and on associated altered oxidative stress markers in the brain of rats. METHODS: The extract was administered orally in three doses (100, 200, and 400 mg/kg) for a period of 21 days. SCOP was administered in the dose of 1.0 mg/kg intraperitoneally. The Morris water maze and passive avoidance step-down tasks were performed to assess cognitive functions. At the end of the study, oxidative stress parameters namely, malondialdehyde (MDA) and reduced glutathione (GSH) were also analyzed in the brain tissue of rats. RESULTS: SCOP-treated group showed significantly impaired acquisition and retention of memory as compared to the saline- and vehicle-treated groups. Pretreatment with CZ extract (200 and 400 mg/kg) for 21 days significantly reversed SCOP-induced amnesia as evidenced by increased step-down latency in passive avoidance and decreased latency in Morris water maze test compared to the SCOP-treated group. SCOP administration also caused the increase of MDA and reduction of GSH levels. Pretreatment with CZ extract (200 and 400 mg/kg) resulted in a significant decrease in MDA levels and increase in GSH levels as compared to the SCOP-treated animals. DISCUSSION: The results suggest that CZ can induce cognitive improvement in SCOP-treated rats and this effect can be attributed to a certain extent to decreased oxidative stress.

Effect of ovarian sex hormones on non-steroidal anti-inflammatory drug-induced gastric lesions in female rats.

OBJECTIVE: The objective of the following study is to investigate the effect of ovarian sex hormones on gastric ulcer in female rats. MATERIALS AND METHODS: Female rats were treated daily with estrogen (0.05 and 0.1 mg/kg), progesterone (2.0 and 5.0 mg/kg), combined estrogen (0.05 mg/kg) and progesterone (2.0 mg/kg), ranitidine (30 mg/kg) or vehicle for 7 days. Ulcers were induced with aspirin on 7th day. Four hours later, animals were sacrificed and stomach were removed for macroscopic and biochemical examination. RESULTS: Estrogen in 0.05 and 0.1 doses showed 32% and 18% of ulcer inhibition, respectively, progesterone 09% and 14% inhibition in 2.0 and 5.0 mg/kg doses, respectively, whereas combined estrogen and progesterone showed 23% and ranitidine showed 60% inhibition. However, the inhibition attained and the stomach malondialdehyde and glutathione levels in sex hormone treated groups were not statistically significant when compared to control group. CONCLUSION: At the tested doses, these ovarian sex hormones neither worsen nor protect against aspirin-induced gastric lesions in female rats.

Anticonvulsant activity of Aloe vera leaf extract in acute and chronic models of epilepsy in mice.

OBJECTIVES: The effect of Aloe vera in epilepsy has not yet been explored. This study was done to explore the effect of aqueous extract of Aloe vera leaf powder on three acute and one chronic model of epilepsy. METHODS: In acute study, aqueous extract of Aloe vera leaf (extract) powder was administered in doses 100, 200 and 400 mg/kg p.o. Dose of 400 mg/kg of Aloe vera leaf extract was chosen for chronic administration. Oxidative stress parameters viz. malondialdehyde (MDA) and reduced glutathione (GSH) were also estimated in brain of kindled animals. KEY FINDINGS: In acute study, Aloe vera leaf (extract) powder in a dose-dependent manner significantly decreased duration of tonic hind limb extension in maximal electroshock seizure model, increased seizure threshold current in increasing current electroshock seizure model, and increased latency to onset and decreased duration of clonic convulsion in pentylenetetrazole (PTZ) model as compared with control group. In chronic study, Aloe vera leaf (extract) powder prevented progression of kindling in PTZ-kindled mice. Aloe vera leaf (extract) powder 400 mg/kg p.o. also reduced brain levels of MDA and increased GSH levels as compared to the PTZ-kindled non-treated group. CONCLUSIONS: The results of study showed that Aloe vera leaf (extract) powder possessed significant anticonvulsant and anti-oxidant activity.

Augmented primary humoral immune response and decreased cell-mediated immunity by Murraya koenigii in rats.

BACKGROUND: Murraya koenigii (Rutaceae) (curry patta: Hindi) of the family Rutaceae is used in the traditional Indian system of medicine for its immunomodulatory properties. The essential oil of the leaves of M. koenigii possesses antimicrobial, antifungal, and pesticidal activities and is used for the treatment of amebiasis, diabetes, and hepatitis. The present study was performed to evaluate the effect of M. koenigii on humoral and cell-mediated immune responses in rats. METHODS: Aqueous extract of M. koenigii leaves was administered orally in a dose of 350 mg/kg. Cell-mediated immunity was assessed by measuring foot pad thickness following sensitization by injection of keyhole limpet hemocyanin and subsequent challenge by the same. Humoral immunity was assessed by measurement of hemagglutination titer to sheep red blood cells (SRBCs). RESULTS: In the humoral immune response, the administration of M. koenigii [350 mg/kg per os (p.o.)] from day 1 to day 7 after sensitization with SRBC on day 0 caused a significant increase in the primary anti-SRBC titer. However, the secondary immune response was decreased significantly (p<0.05) as shown by a decrease in secondary anti-SRBC titer measured on day 11 following a booster dose of antigen on day 8. In the delayed-type hypersensitivity test, M. koenigii (350 mg/kg, p.o.), when administered for 14 days, produced a significant (p<0.05) decrease in foot pad thickness when compared with the control group. CONCLUSIONS: Thus, these results suggest that oral administration of M. koenigii augments primary humoral immune response and decreases cell-mediated immunity.

Possible role of oxidative stress and brain derived neurotrophic factor in triazophos induced cognitive impairment in rats.

Triazophos, O,O-diethyl-1-H-1,2,4-triazol-3-yl phosphorothioate, (TZ) is an organophosphate pesticide widely used as an insecticide in agriculture fields, however, its adverse effects on cognitive function remain unknown till date. The present study was designed to identify the effect of TZ on cognitive function in order to gain an insight into the molecular mechanism(s) probably involved in TZ induced toxicity. Wistar male albino rats were orally administered with TZ at 8.2 mg/kg bw daily for 30 days. Cognitive function was assessed by evaluating step down latency (SDL) in passive avoidance apparatus, transfer latency (TL) on elevated plus maze and escape latency (EL) using morris water maze. The biochemical changes, in terms of malondialdehyde (MDA), reduced glutathione (GSH) and brain derived neurotrophic factor (BDNF) levels were evaluated in hippocampi regions. Relative mRNA expression and protein expression of BDNF were also evaluated. The results demonstrated that rats treated with TZ showed significantly (p < 0.01) reduced SDL and prolonged TL and EL as compared to control group rats. Moreover, significantly low (p < 0.01) mRNA expression and protein levels (p < 0.001) of BDNF, increased MDA and reduced GSH levels were observed in TZ treated rats. The study concludes that chronic exposure to TZ significantly impairs the learning and memory which may be attributed to the significantly reduced mRNA and protein expression of BDNF in hippocampus. Moreover, BDNF is negatively correlated to MDA levels and positively correlated to GSH levels. Hence, it can be suggested that interplay between BDNF and oxidative stress plays an important role in mediating the toxic effects of TZ.

Effect of low level microwave radiation exposure on cognitive function and oxidative stress in rats.

Use of wireless communicating devices is increasing at an exponential rate in present time and is raising serious concerns about possible adverse effects of microwave (MW) radiation emitted from these devices on human health. The present study aimed to evaluate the effects of 900 MHz MW radiation exposure on cognitive function and oxidative stress in blood of Fischer rats. Animals were divided into two groups (6 animals/group): Group I (MW-exposed) and Group II (Sham-exposed). Animals were subjected to MW exposure (Frequency 900 MHz; specific absorption rate 8.4738 x 10(-5) W/kg) in Gigahertz transverse electromagnetic cell (GTEM) for 30 days (2 h/day, 5 days/week). Subsequently, cognitive function and oxidative stress parameters were examined for each group. Results showed significant impairment in cognitive function and increase in oxidative stress, as evidenced by the increase in levels of MDA (a marker of lipid peroxidation) and protein carbonyl (a marker of protein oxidation) and unaltered GSH content in blood. Thus, the study demonstrated that low level MW radiation had significant effect on cognitive function and was also capable of leading to oxidative stress.