Effect of Anacyclus pyrethrum on Pentylenetetrazole-Induced Kindling, Spatial Memory, Oxidative Stress and Rho-Kinase II Expression in Mice

Anacyclus pyrethrum (A. pyrethrum) has been reported to exhibit anticonvulsant activity. In the present study, the effect of hydro-alcoholic extract of A. pyrethrum root (HEAP) on pentylenetetrazole (PTZ) induced kindling, spatial memory, oxidative stress and rho kinase (ROCK II) was assessed. Male albino mice (25–30 g) were used in the study. PTZ (35 mg/kg, i.p. on alternate days) was injected to induce kindling and PTZ (70 mg/kg, i.p) challenge was given 7 days post-kindling. HEAP was administered orally daily in the doses of 100, 250 and 500 mg/kg along with PTZ injections during the kindling process and continued till PTZ challenge post kindling. Spatial memory was assessed using Morris water maze test. Oxidative stress parameters [malondialdehyde (MDA) and reduced glutathione (GSH)] and ROCK II expression were estimated in whole brain at the end of the study. Pre-treatment with HEAP (250 and 500 mg/kg) showed significant increase in the myoclonic jerk latency and delay in the development of kindling. A significant decrease in mortality was observed at higher doses of HEAP (250 and 500 mg/kg). Pre-treatment with HEAP significantly increased the number of platform crossings and decreased the escape latency, as opposed to the PTZ group, thus showing protection against memory deficit. HEAP pre-treatment also attenuated the oxidative stress induced by PTZ kindling. PTZ induced kindling increased the ROCK II expression whereas, HEAP pre-treatment attenuated the increase in ROCK II expression. To conclude, HEAP pre-treatment showed antiepileptic effect and also showed protection against cognitive impairment by decreasing oxidative stress and ROCK II expression in PTZ kindled mice.     

Protective Effect of Nerolidol Against Pentylenetetrazol-Induced Kindling,Oxidative Stress and Associated Behavioral Comorbidities in Mice

The present study was aimed to investigate the effect of nerolidol on the development of kindling and associate oxidative stress and behavioral comorbidities. Kindling was induced by repeated injections of a sub-convulsive dose of pentylenetetrazol (PTZ-35 mg/kg; i.p.), at an interval of 48?±?2 h for 43 days (21 injections). Nerolidol was administered daily in three doses (12.5, 25 and 50 mg/kg) along with alternate day PTZ injection. To access behavioral comorbidities, animals were subjected to tail suspension test (TST) and passive shock avoidance (PSA) test to evaluate the associated depression and memory impairment respectively on the last day of PTZ administration. Following behavioral assessment, neurotransmitter level and oxidative stress markers were evaluated in brain. The results showed that nerolidol significantly suppressed the progression of kindling. Also, nerolidol ameliorates the kindling associated depression and memory impairment as indicated by decreased immobility time and increased step down latency, respectively, as compared to vehicle control animals. Further, these behavioral observations were complimented with corresponding neurochemical and oxidative stress markers changes. In conclusion, the results of present study showed that nerolidol treatment has protective effect against PTZ-induced kindling and associated oxidative stress and behavioral comorbidities.     

Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment

Oxidative stress is a critical contributing factor to age-related neurodegenerative disorders. Therefore, the inhibition of oxidative damage, responsible for chronic detrimental neurodegeneration, is an important strategy for neuroprotective therapy. Withania somnifera (WS) extract has been reported to have potent antioxidant and free radical quenching properties in various disease conditions. The present study evaluated the hypothesis that WS extract would reduce oxidative stress-associated neurodegeneration after intracerebroventricular injection of streptozotocin (ICV-STZ) in rats. To test this hypothesis, male Wistar rats were pretreated with WS extract at doses of 100, 200, and 300 mg/kg body weight once daily for 3 weeks. On day 22nd, the rats were infused bilaterally with ICV-STZ injection (3 mg/kg body weight) in normal saline while sham group received only saline. Two weeks after the lesioning, STZ-infused rats showed cognitive impairment in the Morris water maze test. The rats were sacrificed after 3 weeks of the lesioning for the estimation of the contents of lipid peroxidation, reduced glutathione, and activities of glutathione reductase, glutathione peroxidase, and catalase. Pretreatment with WS extract attenuated behavioral, biochemical, and histological alterations significantly in dose-dependent manner in the hippocampus and cerebral cortex of ICV-STZ-infused rats. These results suggest that WS affords a beneficial effect on cognitive deficit by ameliorating oxidative damage induced by streptozotocin in a model of cognitive impairment.     

Risperidone in Ultra Low Dose Protects Against Stress in the Rodent Cold Restraint Model by Modulating Stress Pathways

The present investigation evaluates the anti-stress activity of risperidone (RIS) in the cold restraint stress (CRS) model and related stress pathways. Rats were pretreated with RIS (0.1 and 1.0 mg/kg) for 21 days before subjecting to CRS. Ultra low dose of RIS (ULD; 0.1 mg/kg) in contrast to higher dose (1.0 mg/kg) significantly reduced stress in terms of ulcer index. ULD also reversed stress-induced increase in plasma corticosterone and norepinephrine levels used as markers for the function of hypothalamo-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) respectively. ULD caused dose and brain region (hippocampus, prefrontal cortex and striatum) specific changes to stress-induced perturbations of serotonin, dopamine and its metabolites indicating modulation of brain monoaminergic system (BMS). ULD did not show any extrapyramidal side effects. Thus, the anti-stress effect ULD is probably mediated through the HPA axis, SNS and BMS. The study indicates a potential use of ULD in stress disorders.     

Palm tocotrienol-rich fraction reduced plasma homocysteine and heart oxidative stress in rats fed with a high-methionine diet

Oxidative stress contributes to cardiovascular diseases. We aimed to study the effects of palm tocotrienol-rich fraction (TRF) on plasma homocysteine and cardiac oxidative stress in rats fed with a high-methionine diet. Forty-two male Wistar rats were divided into six groups. The first group was the control. Groups 2–6 were fed 1 % methionine diet for 10 weeks. From week 6 onward, folate (8 mg/kg diet) or palm TRF (30, 60 and 150 mg/kg diet) was added into the diet of groups 3, 4, 5 and 6. The rats were then killed. Palm TRF at 150 mg/kg and folate supplementation prevented the increase in plasma total homocysteine (4.14?±?0.33 and 4.30?±?0.26 vs 5.49?±?0.25 mmol/L, p?<?0.05) induced by a high-methionine diet. The increased heart thiobarbituric acid reactive substance in rats fed with high-methionine diet was also prevented by the supplementations of palm TRF (60 and 150 mg/kg) and folate. The high-methionine group had a lower glutathione peroxidase activity (49?±?3 vs 69?±?4 pmol/mg protein/min) than the control group. This reduction was reversed by palm TRF at 60 and 150 mg/kg diet (p?<?0.05), but not by folate. Catalase and superoxide dismutase activities were unaffected by both methionine and vitamin supplementations. In conclusion, palm TRF was comparable to folate in reducing high-methionine diet-induced hyperhomocysteinemia and oxidative stress in the rats’ hearts. However, palm TRF was more effective than folate in preserving the heart glutathione peroxidase enzyme activity.     

Influence of ferulic acid on circulatory prooxidant-antioxidant status during alcohol and PUFA induced toxicity.

In recent years, there has been an escalation in alcohol abuse and inevitably, alcohol related disorders are becoming an increasingly important cause of morbidity and mortality. Alcohol is known to induce a dose dependent increase in lipid peroxidation. Alcohol related disabilities are more pronounced when taken along with diet rich in polyunsaturated fatty acid (PUFA). The present work aims at analysing the protective role of ferulic acid (FA), a naturally occurring nutritional component on alcohol and PUFA induced oxidative stress. Two different doses of ferulic acid, 20 mg/kg body weight and 40 mg /kg body weight were used for the study. The results showed that the levels of oxidative markers; thiobarbituric acid reactive substances (TBARS), hydroperoxides (HP) and levels of copper (Cu) and ferritin were increased significantly in plasma of alcohol, thermally oxidised PUFA (DeltaPUFA) and alcohol + DeltaPUFA groups, which were decreased significantly on treatment with both the doses of ferulic acid. The activities of enzymic antioxidants viz. superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and non enzymic antioxidants like vitamin C, vitamin E, and reduced glutathione (GSH) and the levels of zinc (Zn) were significantly decreased in alcohol, DeltaPUFA and alcohol + DeltaPUFA groups which were improved significantly on treatment with both the doses of FA. The reduction in oxidative stress was more significant in 20 mg/kg body weight treatment groups compared to 40 mg/kg body weight. Thus from the results obtained, we conclude that FA effectively protects the system against alcohol and PUFA induced oxidative stress.     

The Effect of Different Oral Doses of Hydroalcoholic Extract of Silymarin on the Blood Oxidative Stress Indicators in Streptozotocin Induced Diabetic Rats

The effect of oral administration of different doses of hydroalcoholic extract of silymarin on body weight, glucose concentration and indicators of oxidative stress superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) and malondialdehyde (MDA) was investigated in the present study. Fifty adult male Wistar rats were used. The animals were divided into five groups and oral route of administration was used in control group (0.9 %, NaCl), control group patients (0.9 %, NaCl), diabetic group (100 mg/kg, silymarin), diabetic group (125 mg/kg, silymarin), diabetic group (250 mg/kg, silymarin) for 14 days with gavage. Diabetes was induced by a single injection of streptozotocin (45 mg/kg, i.p.). Before and 3 days after injection, and at 7 and 14 days of treatment, the fasting glucose level and weight were measured. At the end of 14 days, animals were anesthetized with ether and blood samples were taken by heart puncture and were analyzed for oxidative stress indicators. The results showed that hydroalcoholic extract of silymarin can increase the average body weight and decrease glucose and, at the end of 14 days, decrease MDA level and increase the level of antioxidant enzymes (SOD, GPX, CAT) in red blood cells in a dose-dependent manner (P < 0.05). In conclusion, the hydroalcoholic extract of silymarin has an overall beneficial effect on body weight, glucose level and oxidative stress. Therefore, silymarin may reduce oxidative stress via increasing antioxidant enzyme activity.     

Effect of poly herbal formulation,EuMil, on neurochemical perturbations induced by chronic stress

EuMil, a polyherbal formulation consisting of standardised extracts of Withania somnifera (L) Dunal, Ocimum sanctum L, Asparagus racemosus Wilid and Emblica officinalis Gaertn., is used as an anti-stress agent to attenuate the various aspects of stress related disorders. In the present study, the neurochemical mechanisms underlying the anti-stress activity of EuMil were evaluated by measuring the rat brain monoamine neurotransmitter levels and tribulin activity. Chronic electroshock stress (14 days) significantly decreased the nor-adrenaline (NA) and dopamine (DA) levels in frontal Cortex, pons-medulla, hypothalamus, hippocampus and striatal, hypothalamal region, respectively, and increased the 5-hydroxytryptamine (5HT) level in frontal cortex, pons medulla, hypothalamus and hippocampus. Chronic stress, also increased the rat brain tribulin activity. EuMil (100 mg/kg, p.o., 14 days) treatment normalized the perturbed regional NA, DA, 5HT concentrations, induced by chronic stress. EuMil also significantly attenuated the stress-induced increase in the rat brain tribulin activity. The amelioration of chronic stress-induced neurochemical perturbations by EuMil explains the neurochemical mechanisms underlying the observed putative anti-stress activity of the product.     

Novel Ocimumoside A and B as anti-stress agents: modulation of brain monoamines and antioxidant systems in chronic unpredictable stress model in rats

Therapies targeting central stress mechanisms are fundamental for the development of successful treatment strategies. Ocimum sanctum (OS) is an Indian medicinal plant traditionally used for the treatment of various stress-related conditions. Previously, we have isolated and characterized three OS compounds; Ocimarin, Ocimumoside A and Ocimumoside B. However, their role in modulating chronic stress-induced central changes is unexplored. Thus, in the present study the efficacy of these OS compounds have been evaluated on the chronic unpredictable stress (CUS)-induced alterations in the monoaminergic and antioxidant systems in the frontal cortex, striatum and hippocampus, along with the changes in the plasma corticosterone levels. CUS (two different types of stressors daily for seven days) resulted in a significant elevation of plasma corticosterone level, which was reversed to control levels by pretreatment with Ocimumoside A and B (40 mg/kg p.o.), while Ocimarin showed no effect. The levels of NA, DA and 5-HT were significantly decreased in all the three brain regions by CUS, with a selective increase of DA metabolites. A significant decrease in the glutathione (GSH) content, the activities of superoxide dismutase and catalase with a significant increase in the glutathione peroxidase activity and lipid peroxidation was observed in all the three regions of the brain by CUS. The OS compounds alone did not cause any significant change in the baseline values of these parameters. However, Ocimumoside A and B (40 mg/kg body p.o.) attenuated these CUS-induced alterations with an efficacy similar to that of standard anti-stress (Panax quinquefolium; 100 mg/kg p.o.) and antioxidant (Melatonin; 20 mg/kg i.p.) drugs. While, Ocimarin failed to modulate these CUS-induced alterations. Therefore, this is the first report which identified the anti-stress activity of novel Ocimumoside A and B at the level of central monoamines and antioxidant properties, implicating their therapeutic importance in the prevention of stress-related disorders.     

Studies on the protective effects of betaine against oxidative damage during experimentally induced restraint stress in Wistar albino rats

Stress can be defined as physical and psychological modifications that disrupt the homeostasis and the balance of organisms. Stress is known as one of the most important reasons of several diseases. In the present study, the anti-stress effect of betaine was evaluated with reference to its antioxidant property. Wistar albino rats were divided into four groups such as control, betaine, restraint stress (6 h/day for 30 days), and betaine + restraint stress. The oxidative damage was assessed by measuring the protein and corticosterone in plasma, lipid peroxidation, non-enzymic (reduced glutathione), and enzymic antioxidants (glutathione peroxidase, glutathione-S-transferase, catalase, and superoxide dismutase) in the lymphoid organs of thymus and spleen. Followed by the induction of restraint stress, the non-enzymic and enzymic antioxidants were significantly decreased with concomitant increase observed in the levels of corticosterone and lipid peroxidation. Oral pretreatment with betaine (250 mg/kg body weight daily for a period of 30 days) significantly (P < 0.001) prevented the restraint stress-induced alterations in the levels of protein and corticosterone in plasma of experimental groups of rats. It counteracted the restraint stress-induced lipid peroxidation and maintained the antioxidant defense system in the lymphoid tissues at near normal. The findings suggest that betaine possesses significant anti-stress activity, which may be due to its antioxidant property.     

Streptozotocin may provide protection against subsequent oxidative stress of endotoxin or streptozotocin in rats

Endotoxin lipopolysaccharide (LPS) and streptozotocin-induced diabetes are known to cause oxidative stress in vivo. There is some evidence that a sublethal dose of LPS provides protection against subsequent oxidative stress. Because of its wide use as a diabetogenic agent, this study was undertaken to determine if streptozotocin can likewise provide a protective effect against further oxidative stress in rats. Female Sprague–Dawley rats were given streptozotocin (50 mg/kg intraperitoneally once) prior to exposure to either bacterial endotoxin from Salmonella abortus equii (5 mg/kg intraperitoneally) or three additional daily doses of streptozotocin (50 mg/kg intraperitoneally). One week after LPS or streptozotocin treatments, oxidative stress was determined by measuring changes in antioxidant activity (glutathione peroxidase, glutathione reductase, superoxide dismutase, catalase, glutathione S-transferase, and γ-glutamyltranspeptidase) and in concentrations of glutathione, nitrite, and thiobarbituric acid reactants in liver, kidney, intestine, and spleen. High levels of some antioxidants in the LPS-control and streptozotocin-control rats, in contrast to normal levels found in diabetes + LPS and multidose-streptozotocin rats, suggest that streptozotocin, like LPS, may confer a protective effect against subsequent oxidative stress. © 1998 John Wiley & Sons, Inc. J Biochem Toxicol 12: 143–149, 1998     

Embelin Attenuates Intracerebroventricular Streptozotocin-Induced Behavioral,Biochemical, and Neurochemical Abnormalities in Rats

Embelin, the main active constituent of Embelia ribes, has been reported to possess various pharmacological actions, including anti-inflammatory, antioxidant, anticonvulsant, and neuroprotective. The present study was designed to investigate neuroprotective mechanisms and therapeutic potential of embelin against intracerebroventricular streptozotocin (ICV-STZ)-induced experimental sporadic dementia in rats. STZ was infused bilaterally at the dose of (3 mg/kg/1 μl/1 min) ICV on day first and third. Spatial and non-spatial memory was evaluated using Morris water maze and object recognition task in rats. Embelin (2.5, 5, and 10 mg/kg, i.p.) was administrated for 14 days from seventh day onwards after first ICV-STZ infusion in rats. On day 22, rats were sacrificed and hippocampal brain regions were used to identify biochemical, neurochemical, and neuroinflammatory alterations. STZ-infused rats showed significant learning and memory deficit which was associated with an increase in oxidative stress (lipid peroxidation and nitrite), compromised antioxidant defense (reduced glutathione), neurotransmitter alterations (AChE, dopamine, noradrenaline, 5-hydroxytryptamine, gama amino butyric acid, and glutamate), and elevation in neuroinflammatory cytokine (IL-1 β, IL-6, and TNF-α) levels. Embelin dose dependently attenuated STZ-induced cognitive deficit and biochemical alterations and restored hippocampal neurochemical levels. The observed protective effect might be attributed to the antioxidant and anti-inflammatory potential of embelin and its ability to restore hippocampal neurochemistry. Thus, the outcomes of the current study suggest therapeutic potential of embelin in cognitive disorders such as sporadic Alzheimer’s disease (SAD).     

Induction of oxidative stress and histopathological changes by sub-chronic doses of triazophos

The effect of triazophos (O, O-diethyl O-1-phenyl-1 H-1, 2, 4-triazol-3-yl phosphorothioate), a widely used insecticide was studied on the induction of oxidative stress and histological alterations at sub-chronic doses in male albino rats. Oral administration of triazophos at concentrations of 1.64, 3.2 and 8.2 mg/kg body wt for 30 days produced dose as well as time-dependent increase in the lipid peroxidation (determined by malondialdehyde levels) and glutathione-S-transferase (GST) activity in serum with aconcomitant decrease in ferric reducing ability of plasma (FRAP) and blood glutathione (GSH) content. Histopathological examination of liver of triazophos-treated rats showed significant and progressive degenerative changes as compared to control, which could be due to induction of oxidative stress. However, no significant histopathological changes were observed in spleen, kidney and brain at either dose of triazophos with respect to control. These results indicated that oral administration of triazophos was associated with enhanced lipid peroxidation and compromised antioxidant defence in rats in dose and time-dependent manner. Thus the present study demonstrated for the first time the role of oxidative stress as the important mechanism involved in the stimulation of hepatic histoarchitectural alterations at sub-chronic doses of triazophos in rats.     

Effect of Chronic N-Acetyl Cysteine Administration on Oxidative Status in the Presence and Absence of Induced Oxidative Stress in Rat Striatum

Antioxidants have possible therapeutic value in neurodegenerative disorders, although they may have pro-oxidant effects under certain conditions. Glutathione (GSH) is a key free radical scavenger. N-acetylcysteine (NAC) bolsters GSH and intracellular cysteine and also has effective free radical scavenger properties. The effects of chronic NAC administration (50 mg/kg/day, 500 mg/kg/day, 1500 mg/kg/day × 21 days) on cellular markers of oxidative status was studied in striatum of healthy male Sprague-Dawley rats as well as in animals with apparent striatal oxidative stress following chronic haloperidol treatment (1.5 mg/kg/day × 3 weeks). In non-haloperidol treated animals, NAC 50 and 500 mg/kg did not affect oxidative status, although NAC 1,500 mg/kg significantly increased striatal superoxide levels, decreased lipid peroxidation and increased consumption of reduced glutathione (GSH). Haloperidol alone evoked a significant increase in superoxide and lipid peroxidation. All NAC doses blocked haloperidol induced increases in superoxide levels, while NAC 500 mg/kg and 1,500 mg/kg prevented haloperidol-associated lipid peroxidation levels and also increased the GSSG/GSH ratio. NAC may protect against conditions of striatal oxidative stress, although possible pro-oxidative actions at high doses in otherwise healthy individuals, e.g. to offset worsening of neurodegenerative illness, should be viewed with caution.     

Protective effect of Piper betle leaf extract against cadmium-induced oxidative stress and hepatic dysfunction in rats

The present study was undertaken to examine the attenuative effect of Piper betle leaf extract (PBE) against cadmium (Cd) induced oxidative hepatic dysfunction in the liver of rats. Pre-oral supplementation of PBE (200 mg/kg BW) treated rats showed the protective efficacy against Cd induced hepatic oxidative stress. Oral administration of Cd (5 mg/kg BW) for four weeks to rats significantly (P > 0.05) elevated the level of serum hepatic markers such as serum aspartate transaminase (AST), serum alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (GGT), bilirubin (TBRNs), oxidative stress markers viz., thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH), protein carbonyls (PC) and conjugated dienes (CD) and significantly (P > 0.05) reduced the enzymatic antioxidants viz., superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PD) and non-enzymatic antioxidants Viz., reduced glutathione (GSH), total sulfhydryls (TSH), vitamin C and vitamin E in the liver. Pre-oral supplementation of PBE (200 mg/kg BW) in Cd intoxicated rats, the altered biochemical indices and pathological changes were recovered significantly (P > 0.05) which showed ameliorative effect of PBE against Cd induced hepatic oxidative stress. From the above findings, we suggested that the pre-administration of P. betle leaf extract exhibited remarkable protective effects against cadmium-induced oxidative hepatic injury in rats.     

Possible GABAergic Modulation in the Protective Effect of Zolpidem in Acute Hypoxic Stress-induced Behavior Alterations and Oxidative Damage

Hypoxia is an environmental stressor that is known to elicit alterations in both the autonomic nervous system and endocrine functions. The free radical or oxidative stress theory holds that oxidative reactions are mainly underlying neurodegenerative disorders. In fact among complex metabolic reactions occurring during hypoxia, many could be related to the formation of oxygen derived free radicals, causing a wide spectrum of cell damage. In present study, we investigated possible involvement of GABAergic mechanism in the protective effect of zolpidem against acute hypoxia-induced behavioral modification and biochemical alterations in mice. Mice were subjected to acute hypoxic stress for a period of 2 h. Acute hypoxic stress for 2 h caused significant impairment in locomotor activity, anxiety-like behavior, and antinocioceptive effect in mice. Biochemical analysis revealed a significant increased malondialdehyde, nitrite concentrations and depleted reduced glutathione and catalase levels. Pretreatment with zolpidem (5 and 10 mg/kg, i.p.) significantly improved locomotor activity, anti-anxiety effect, reduced tail flick latency and attenuated oxidative damage (reduced malondialdehyde, nitrite concentration, and restoration of reduced glutathione and catalase levels) as compared to stressed control (hypoxia) (P < 0.05). Besides, protective effect of zolpidem (5 mg/kg) was blocked significantly by picrotoxin (1.0 mg/kg) or flumazenil (2 mg/kg) and potentiated by muscimol (0.05 mg/kg) in hypoxic animals (P < 0.05). These effects were significant as compared to zolpidem (5 mg/kg) per se (P < 0.05). Present study suggest that the possible involvement of GABAergic modulation in the protective effect of zolpidem against hypoxic stress.     

The Protective Effect of Physalis peruviana L. Against Cadmium-Induced Neurotoxicity in Rats

The present study was carried out to investigate the protective effect of Physalis peruviana L. (family Solanaceae) against cadmium-induced neurotoxicity in rats. Adult male Wistar rats were randomly divided into four groups. Group 1 was used as control. Group 2 was intraperitoneally injected with 6.5 mg/kg bwt of cadmium chloride for 5 days. Group 3 was treated with 200 mg/kg bwt of methanolic extract of Physalis (MEPh). Group 4 was pretreated with MEPh 1 h before cadmium for 5 days. Cadmium treatment induced marked disturbances in neurochemical parameters as indicating by significant (p?p?p?p?p?2+, Cl^?, DA, 5-HT, and serotonin metabolite, 5-HIAA. These data indicated that Physalis has a beneficial effect in ameliorating the cadmium-induced oxidative neurotoxicity in the brain of rats.     

Protection against paracetamol-induced hepatic injury by prazosin pre-treatment in CD-1 mice

A synergistic depletion of glutathione has been suggested to be one critical factor in the hepatic injury in mice induced by non-toxic doses of paracetamol (APAP) when co-administered with -adrenergic agonists. Prazosin (an -adrenergic antagonist) could confer hepatoprotection following a toxic APAP dose (530 mg/kg) by increasing glutathione levels and enhancing bioinactivation by glucuronidation and glutathione conjugation. The effect of prazosin pre-treatment on APAP-induced gluthathione depletion and bioinactivation in vivo was assessed. Prazosin (15 mg/kg) pre-treatment provided protection against APAP-induced hepatic injury as evidenced by a significant decrease in serum transaminase (ALT) levels after 5 h (p < 0.05). Interestingly, prazosin pre-treatment did not prevent the dramatic depletion of glutathione by high dose APAP and it had no effect on the quantity of the glutathione conjugate formed. However, prazosin pre-treatment caused a significant increase in recovery of the administered dose (530 mg/kg) as the glucuronide metabolite (p < 0.05). UDP-glucuronosyltransferase (UGT) is involved in the bioinactivation of APAP by glucuronidation and we showed that prazosin had no effect on microsomal UGT kinetics. Thus, prazosin had no effect on either APAP-mediated glutathione depletion or the extent of APAP-glutathione conjugate formation and may be affecting other mechanisms to reduce oxidative stress caused by a toxic dose of APAP.     

Combination of Omega-3 Fatty Acids,Lithium, and Aripiprazole Reduces Oxidative Stress in Brain of Mice with Mania

Manic episode in bipolar disorder (BD) was evaluated in the present study with supplementation of omega-3 fatty acids in combination with aripiprazole and lithium on methylphenidate (MPD)-induced manic mice model. Administration of MPD 5 mg/kg bw intraperitoneally (i.p.) caused increase in oxidative stress in mice brain. To retract this effect, supplementation of omega-3 fatty acids 1.5 ml/kg (p.o.), aripiprazole 1.5 mg/kg bw (i.p.), and lithium 50 mg/kg bw (p.o) were given to mice. Omega-3 fatty acids alone and in combination with aripiprazole- and lithium-treated groups significantly reduced the levels of superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation products (thiobarbituric acid reactive substances) in the brain. MPD treatment significantly decreased the reduced glutathione (GSH) level and glutathione peroxidase (GPx) activity, and they were restored by supplementation of omega-3 fatty acids with aripiprazole and lithium. There is no remarkable difference in the effect of creatine kinase (CK) activity between MPD-induced manic model and the treatment groups. Therefore, our results demonstrate that oxidative stress imbalance and mild insignificant CK alterations induced by administration of MPD can be restored back to normal physiological levels through omega-3 fatty acids combined with lithium and aripiprazole that attributes to effective prevention against mania in adult male Swiss albino mice.     

<Emphasis Type="Italic">Arbutus andrachne</Emphasis> L. Reverses Sleep Deprivation-Induced Memory Impairments in Rats

Sleep deprivation (SD) is associated with cognitive deficits. It was found to affect the hippocampus region of the brain by impairing memory formation. This impairment is suggested to be caused by elevation in oxidative stress in the body, including the brain during SD. It was hypothesized that the methanolic extract of the fruits of Arbutus andrachne L. (Ericaceae) will prevent chronic SD-induced impairment of hippocampal memory via its antioxidative properties. The methanolic extract of the fruits of A. andrachne was evaluated for its beneficial properties to reverse SD-induced cognitive impairment in rats. Animals were sleep deprived for 8 weeks using a multiple platform model. The extract was administered i.p. at three doses (50, 200, and 500 mg/kg). Behavioral studies were conducted to test the spatial learning and memory using radial arm water maze (RAWM). In addition, the hippocampus was dissected to analyze the following oxidative stress markers: glutathione (GSH), oxidized glutathione (GSSG), GSH/GSSG, glutathione peroxidase (GPx), and catalase. Chronic SD impaired short- and long-term memories (P < 0.05). Treatment of animals with A. andrachne fruit extract at all doses prevented long-term memory impairment induced by SD while such treatment prevented short-term memory impairment only at 200 and 500 mg/kg dose levels. Moreover, A. andrachne fruit extract normalized the reduction in the hippocampus GSH/GSSG ratio and activity of GPx, and catalase (P < 0.05) induced by chronic sleep deprivation. Chronic sleep deprivation impaired both short- and long-term memory formation, while methanolic extract of A. andrachne fruits reversed this impairment, probably through normalizing oxidative stress in the hippocampus.