Like Symptoms In Rats Research Articles

Neuroprotective effect of silymarin against 3‐nitropropionic acid‐induced Huntington’s like symptoms in rats

AbstractBackgroundNeuroprotective effect of silymarin against 3‐nitropropionic acid‐induced Huntington’s like symptoms in rats.MethodHuntington's disease (HD) is a chronic neurodegenerative and hyperkinetic movement disorder characterized by degeneration of GABAergic medium spiny neurons, mainly affecting striatum and cortex. 3‐nitropropionic acid (3‐NP) acts as a suitable animal model to induce HD like symptoms in rats. Therefore, the present study aimed to investigate the neuroprotective effect of silymarin against 3‐NP induced HD like symptoms in rats. Rats were administered 3‐NP (10 mg/kg; i.p) for 21 days, whereas silymarin (50, 100 and 200 mg/kg; p.o) was given once a day, 1 hour before the 3‐NP treatment for 21 days. Body weight and behavioral parameters (rotarod, open field test, and narrow beam walk activities) were assessed on 1st, 7th, 14th, and 21st days. On the 22nd day, the animals were sacrificed, and the rat striatum and cortex were isolated to perform biochemical parameters (lipid peroxidation; glutathione; superoxide dismutase; nitrite and catalase).ResultSystemic 3‐NP treatment significantly reduced body weight, motor‐coordination, and oxidative defense. Pretreatment with silymarin significantly attenuated the 3‐NP induced alterations in body weight, locomotor activities, and oxidative defense.ConclusionOur results revealed that in a 3‐NP model of HD, silymarin could underlie the possible neuroprotective effect, which may provide insight into the therapeutic potential of silymarin for HD.

Naringenin mitigates behavioral alterations and provides neuroprotection against 3-nitropropinoic acid-induced Huntington’s disease like symptoms in rats

ABSTRACT Background Naringenin is a powerful antioxidant and anti-inflammatory flavonoid which has been widely used as a therapeutic agent in various toxic models. However, few studies have clearly discussed the neuromodulatory effects of naringenin against different neurodegenerative disorders. Aim We investigated the neuroprotective efficacy of naringenin against 3-nitropropionic acid (3-NP)-induced neurobehavioral, biochemical and histopathological alterations in rats. Methods Albino Wistar rats were randomly divided into three experimental groups. Group 1, the vehicle administered group, received saline. Group 2 received 3-NP (20 mg/kg body weight, i.p.) for 4 consecutive days. Group 3 received naringenin (50 mg/kg body weight, p.o.) twice daily for a period of 4 days, 30 min before and 6 h after the 3-NP administration. On the 5th day, neurobehavioral experiments were performed to access the behavioral outcomes and the striatum tissue was used for analysis of the monoamine oxidase (MAO) activity and serotonin (5-HT) levels. In addition, astrocytes activation was observed by glial fibrillary acidic protein (GFAP) immunostaining. Results Our results showed that naringenin co-treatment provides neuroprotection against 3-NP-induced neurological disorders. Naringenin also increased the MAO activity and 5-HT levels in the striatum. Moreover, co-treatment with naringenin reduced the expression of GFAP protein in the striatal part and significantly attenuated the neuronal cell death. The findings of the present study suggest that naringenin provides neuroprotection and mitigates neurobehavioral alterations in experimental rats. Conclusion The results show that co-treatment with naringenin ameliorates 3-NP-induced HD-like symptoms in rats.

Neuroprotective effect of standardized extracts of three Lactuca sativa Linn. varieties against 3-NP induced Huntington’s disease like symptoms in rats

ABSTRACT Objectives The study was aimed to evaluate the efficacy of three commonly consumed Lactuca sativa (LS) Linn. varieties viz., Grand rapid, Lollo rosso and Iceberg (Asteraceae) against 3-NP induced HD like symptoms in rats. Methods Ethanol extracts of leaves of three LS varieties were prepared, and standardized on the basis of quercetin content using HPLC. These extracts (100 and 200 mg kg, p.o. for 20 days) were evaluated for their neuroprotective effect against 3-NP (10 mg/kg, i.p. for 14 days) induced neurotoxicity in male Wistar rats. The extract that exhibited maximum activity was successively fractionated using hexane, ethyl acetate, n-butanol and aqueous in increasing order of polarity. These fractions were also evaluated (dose equivalent to the dose of the extract of LS variety exhibiting maximum activity) for their neuroprotective effect. The protective effect of extracts and fractions was evaluated using different behavioral (rota rod, actophotometer, beam walk and Morris water maze) and biochemical (malondialdehyde, nitrite, superoxide dismutase, catalase and reduced glutathione) parameters. Results 3-NP elicit marked deterioration in motor coordination, locomotor activity and memory in comparison to control group. Standardized ethanol extract of grand rapid (200 mg/kg) exhibited maximum activity amongst the three tested varieties. Therefore, its fractions were also evaluated, and n-butanol fraction (40 mg/kg) exhibited maximum attenuation of 3-NP induced HD like symptoms which was evident from improved behavioral and biochemical parameters. Discussion The results exhibit that LS (Grand rapid variety) prophylaxis mitigated 3-NP induced neurotoxicity and HD like symptoms in rats due to its potent antioxidant potential.

Exploring the beneficial effects and possible mechanisms of repeated episodes of whole-body hypoxic perconditioning in rat model of preeclampsia

ABSTRACT Aim The study explored the beneficial effects of repeated episodes of whole body hypoxic perconditioning (WHPC) on preeclampsia (PE)-like symptoms in rats. Material and Methods PE was induced by administration of L-NAME (75 mg/kg) and WHPC was performed by exposing rats to low O2 (8%) and normal O2 of 10 min each in four alternate cycles. Results L-NAME induced PE like symptoms in rats along with a decrease in the cystathionine-β-synthase (CBS) activity in the placental tissue, plasma levels of H2S and NO metabolites in pregnant rats. Two (GD9, GD14) and three episodes (GD9, GD14 and GD18) of WHPC improved PE-like symptoms with an increase in CBS activity and H2S levels. CBS inhibitor, amino-oxyacetic acid abolished the beneficial effects of three episodes of WHPC; while H2S donor, 4-methylbenzenecarbothioamide, 4-MBC attenuated PE-like symptoms. Conclusion WHPC attenuates L-NAME-induced PE-like symptoms due to increase in CBS activity and H2S-production.

Piperine mitigates behavioral impairments and provides neuroprotection against 3-nitropropinoic acid-induced Huntington disease-like symptoms

ABSTRACT Background: Piperine (PIP) is a powerful anti-oxidant and anti-inflammatory alkaloid which has been widely used in the treatment of various pathological conditions. However, few studies have clearly discussed the protective effects and potential mechanism of PIP in different neurological diseases. The aim of this study was to investigate the neuroprotective effect of PIP against 3-nitropropioninc acid (3-NP) induced neurobehavioral, biochemical and histopathological alterations in animals. Methods: Adult male Wistar rats were randomly divided into three groups. Group 1, the vehicle administered control group, received normal saline (p.o.). Group 2 received 3-NP (20 mg/kg.b.wt., i.p.) for 4 consecutive days. Group 3 received PIP (10 mg/kg.b.wt., p.o.) twice daily for a period of 4 days, 30 min before and 6 h after the 3-NP injection. Upon termination of treatment schedule, behavioral experiments were performed to access the behavioral outcomes. The brain striatal tissue was used for the estimation of monoamine oxidase activity and serotonin level. In addition, astrocytes activation was observed by GFAP immunostaining. Results: Our results showed that 3-NP induced behavioral impairments are attenuated by PIP co-treatment. Next, the extent of neuronal loss and astrocytes activation was reduced in the striatal brain region in PIP treated rats. Finally, it was observed that PIP alleviated the behavioral, biochemical, immunohistochemical and histological alterations. Conclusion: The results of the current study reveal the neuroprotective competency of PIP against Huntington disease like symptoms in rats.

Anti-hyperglycemic effect of Swertia chirata root extract on indinavir treated rats

Background: Indinavir belongs to class of protease inhibitors which is widely used for the treatment of AIDS. Treatment with Indinavir may induce diabetic like symptoms and prolonged treatment leads to diabetes mellitus. Aim and Objectives: To study the anti-hyperglycemic effect of Swertia chirata root extract on indinavir treated rats. Materials and Methods: Swiss albino Wister rats were divided into seven groups of seven animals each. Group I (control) received normal saline (oral), Group II received Indinavir 216 mg/kg (oral), Group III received S. chirata root extract 500 mg/kg (oral), Group IV received pioglitazone 4 mg/kg (oral), Group V received metformin 180 mg/kg (oral), Group VI received pioglitazone 4 mg/kg (oral) along with S. chirata root extract 500 mg/kg (oral), and Group VII received metformin 180 mg/kg (oral) along with S. chirata root extract 500 mg/kg (oral). All the groups (Except control) were treated with indinavir 216 mg/kg (oral) for 15 days. Moreover, the treatment with extract and standard drug is carried out from day 8 to day 15. The biochemical estimations - such as serum glucose, Insulin, and lipid levels - were carried on day 15. Statistical analysis is performed using one-way analysis of variance followed by Bonferroni’s multiple comparison test. Results: The group treated with indinavir (216 mg/kg) showed significant (P < 0.05) increase in biochemical parameters compared to the other groups. This shows that indinavir is capable of producing diabetic like symptoms in rats. The group treated with S. chirata root extract (500 mg/kg) decreases glucose and insulin levels and also improves lipid levels which are almost similar to the effect produced by the standard drug metformin and pioglitazone. Conclusion: The treatment with indinavir produces elevated glucose, insulin, and lipid levels. The groups treated with S. chirata root extract showed improved glucose, insulin and lipid profile in Indinavir treated rats.

Sertraline and venlafaxine improves motor performance and neurobehavioral deficit in quinolinic acid induced Huntington's like symptoms in rats: Possible neurotransmitters modulation.

Huntington Disease is autosomal, fatal and progressive neurodegenerative disorder for which clinically available drugs offer only symptomatic relief. Emerging strides have indicated that antidepressants improve motor performance, restore neurotransmitters level, ameliorates striatal atrophy, increases BDNF level and may enhance neurogenesis. Therefore, we investigated sertraline and venlafaxine, clinically available drugs for depression with numerous neuroprotective properties, for their beneficial effects, if any, in quinolinic acid induced Huntington's like symptoms in rats. Rats were administered quinolinic acid (QA) (200 nmol/2μl saline) intrastriatal bilaterally on 0day. Sertraline and venlafaxine (10 and 20mg/kg, po) each were administered for 21days once a day. Motor performance was assessed using rotarod test, grip strength test, narrow beam walk test on weekly basis. On day 22, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH and Nitrite), neuroinflammation (TNF-α, IL-1β and IL-6) and neurochemical analysis (GABA, glutamate, norepinephrine, dopamine, serotonin, DOPAC, HVA and 5-HIAA). QA treatment significantly altered body weight, motor performance, oxidative defense (increased LPO, nitrite and decreased GSH), pro-inflammatory cytokines levels (TNF-α, IL-6 and IL-1β), neurochemical level (GABA, glutamate, nor-epinephrine, dopamine, serotonin, HVA, DOPAC, 5-HIAA). Sertraline and venlafaxine at selected doses significantly attenuated QA induced alterations in striatum. The present study suggests that modulation of monoamines level, normalization of GABA and glutamatergic signaling, anti-oxidant and anti-inflammatory properties could underlie the neuroprotective effect of sertraline and venlafaxine in QA induced Huntington's like symptoms.

Beneficial effect of antidepressants against rotenone induced Parkinsonism like symptoms in rats

Parkinson’s disease is a second most common age-related neurodegenerative disorder characterized by the loss of DA neurons of SNpc region of the midbrain. Neurotransmitter dysfunction is involved in the pathogenesis of PD. Antidepressants like venlafaxine and sertraline expected to improve Parkinsonism like symptoms by modulating the levels of various neurotransmitters. The neuroprotective role of antidepressants is well explored in various CNS disorders. Therefore, this study was designed to explore and compare the mechanistic role of different antidepressants (venlafaxine and sertraline) against rotenone induced Parkinsonism like symptoms in rats. Rats were administrated with rotenone (1.5mg/kg/day; s.c.) daily for a period of 28 days. Venlafaxine (10 and 20mg/kg; p.o.), sertraline (10 and 20mg/kg; p.o.) and Levodopa combination with Carbidopa (10mg/kg; p.o.) were administered daily starting from 7th day one hour prior to rotenone administration. Behavioral parameters (body weight, rotarod, grip strength, narrow beam walk and open field) were assessed on weekly basis. On 28th day, animals were sacrificed and striatum were isolated for biochemical (LPO, GSH and nitrite), neuroinflammatory (TNF-α, IL-1β and IL-6), neurochemical (DA, NE, 5-HT, GABA, Glutamate, DOPAC, HVA and 5-HIAA) and mitochondrial complex-I estimation. Rotenone administration significantly reduced body weight, motor coordination, oxidative defense, increased pro-inflammatory mediators and decreased level of catecholamines. Pre-treatment with venlafaxine and sertraline significantly attenuated the alteration in behavioral, oxidative stress, neuroinflammatory, mitochondrial and catecholamines level in striatum. The study provides a hope that these drugs could be used as adjuvant therapy in the management and treatment of PD.

Combined effect of hydrogen sulphide donor and losartan in experimental diabetic nephropathy in rats.

BackgroundDiabetic nephropathy (DN) is one of the complex complications of Diabetes Mellitus (DM). The present study has been designed to examine protective role of hydrogen Sulphide (H2S) donor against streptozotocin (STZ) -induced behavioral, oxidative abnormalities and its DN like symptoms in rats.MethodsFor the induction of DN single intraperitoneal administration of STZ (45 mg/kg) was given till third week. Behavioral parameters were measured on 1st, 7th, 21st and 42nd days and biochemical parameters were performed on 42nd day. All the drug treatments [NaHS (10 & 30 μmol/kg i.p), DL-propargylglycine (10 mg/kg i.p), standard drug- Losartan (5 mg/kg p.o)] were given for 3 weeks staring from 21st day after the STZ injection.ResultsThree weeks treatment with sodium hydrosulphide (NaHS) (10 and 30 μmol/kg i.p,) significantly attenuated the behavioral and biochemical abnormalities in STZ-treated animals. DL-propargylglycine (10 mg/kg i.p) pretreatment with sub-effective dose of NaHS (30 μmol/kg i.p) significantly reversed the protective effect of NaHS. However, combination of both NaHS (30 μmol/kg i.p) and standard drug losartan (5 mg/kg p.o) potentiated their effects as compared to their effect alone.ConclusionThe results of the present study suggest that H2S treatment showed significant improvement in behavioral and biochemical abnormalities induced by STZ administration. Thus H2S represents a target of treatment to prevent the progression of complications by DN.

Protective Effect of Spermidine Against Excitotoxic Neuronal Death Induced by Quinolinic Acid in Rats: Possible Neurotransmitters and Neuroinflammatory Mechanism.

Huntington disease is hyperkinetic movement disorder characterized by selective and immense degradation of GABAergic medium spiny neurons in striatum. Quinolinic acid (QA)-induced neurotoxicity involves a cascade of events such as excitotoxicity, ATP depletion, oxidative stress, neuroinflammation, as well as selective GABAergic neuronal loss. Therefore, we investigated spermidine, an endogenous molecule with free radical scavenging, anti-inflammatory, and N-methyl-D-aspartate receptor antagonistic properties, for its beneficial potential if any, in QA-induced Huntington's like symptoms in rats. Rats were administered with QA (200 nmol/2 µl saline) bilaterally on 0 day. Spermidine (5 and 10 mg/kg, p.o.) was administered for 21 days once a day. Behavioral parameters (body weight, locomotor activity, grip strength, and narrow beam walk) observations were done on 1st, 7th, 14th, and 21st day after QA treatment. On 21st day, animals were sacrificed and rat striatum was isolated for biochemical (LPO, GSH, Nitrite), neuroinflammation (TNF-α, IL-1β, and IL-6), and neurochemical analysis (GABA, glutamate, dopamine, norepinephrine, serotonin, DOPAC, HVA, 5-HIAA, adenosine, adenine, hypoxanthine, and inosine). QA treatment significantly altered body weight, locomotor activity, motor coordination, oxidative defense (increased LPO, nitrite, and decreased GSH), pro-inflammatory levels (TNF-α, IL-6 and IL-1β), GABA, glutamate, catecholamines level (norepinephrine, dopamine, and serotonin and their metabolites), and purines level (adenosine, inosine, and hypoxanthine). Spermidine (5 and 10 mg/kg, p.o.) significantly attenuated these alterations in body weight, motor impairments, oxidative stress, neuroinflammatory markers, GABA, glutamate, catecholamines, adenosine, and their metabolites levels in striatum. The neuroprotective effect of spermidine against QA-induced excitotoxic cell death is attributed to its antioxidant, N-methyl-D-aspartate receptor antagonistic, anti-inflammatory properties, and prevention of neurotransmitters alteration in striatum.

P.5.d.005 Role of cannabinoid CB2 receptor in Parkinson's disease

Parkinson’s disease is a second most common age-related neurodegenerative disorder characterized by the loss of DA neurons of SNpc region of the midbrain. Neurotransmitter dysfunction is involved in the pathogenesis of PD. Antidepressants like venlafaxine and sertraline expected to improve Parkinsonism like symptoms by modulating the levels of various neurotransmitters. The neuroprotective role of antidepressants is well explored in various CNS disorders. Therefore, this study was designed to explore and compare the mechanistic role of different antidepressants (venlafaxine and sertraline) against rotenone induced Parkinsonism like symptoms in rats. Rats were administrated with rotenone (1.5 mg/kg/day; s.c.) daily for a period of 28 days. Venlafaxine (10 and 20 mg/kg; p.o.), sertraline (10 and 20 mg/kg; p.o.) and Levodopa combination with Carbidopa (10 mg/kg; p.o.) were administered daily starting from 7th day one hour prior to rotenone administration. Behavioral parameters (body weight, rotarod, grip strength, narrow beam walk and open field) were assessed on weekly basis. On 28th day, animals were sacrificed and striatum were isolated for biochemical (LPO, GSH and nitrite), neuroinflammatory (TNF-α, IL-1β and IL-6), neurochemical (DA, NE, 5-HT, GABA, Glutamate, DOPAC, HVA and 5-HIAA) and mitochondrial complex-I estimation. Rotenone administration significantly reduced body weight, motor coordination, oxidative defense, increased pro-inflammatory mediators and decreased level of catecholamines. Pre-treatment with venlafaxine and sertraline significantly attenuated the alteration in behavioral, oxidative stress, neuroinflammatory, mitochondrial and catecholamines level in striatum. The study provides a hope that these drugs could be used as adjuvant therapy in the management and treatment of PD.

Protective effect of quercetin against acetic acid induced inflammatory bowel disease (IBD) like symptoms in rats: Possible morphological and biochemical alterations

BackgroundInflammatory bowel disease (IBD) is characterized by most common symptoms such as rectal bleeding. Lack of specific, curative treatments tempted us to evaluate the therapeutic efficacy of quercetin against acetic acid induced IBD like symptoms. MethodsAnimals were randomly divided into five groups (n=6): naive, control, sulphasalazine and quercetin, and were pretreated for three days. Colitis was induced by intra-rectal administration of 3% acetic acid. ResultsPretreatment with sulphasalazine or quercetin significantly attenuated the biochemical and morphological alterations in the colon induced by acetic acid in rats. ConclusionsThe findings of the study suggest the possible role of quercetin as therapeutics in IBD.

Neuroprotective activity of L-theanine on 3-nitropropionic acid-induced neurotoxicity in rat striatum

The present study has been designed to investigate the protective effect of L-theanine against 3-nitropropionic acid (3-NP)-induced Huntington's disease (HD)-like symptoms in rats. The present experimental protocol design includes systemic 3-NP acid (10 mg/kg intraperitonially) treatment for 14 d. L-theanine (100 and 200 mg/kg) was given orally, once a day, 1 h before 3-NP acid treatment for 14 d. Body weight and behavioral parameters (Morris water maze, open field test (OFT), forced swim test (FST) and rotarod activity) were assessed on 1st, 5th, 10th and 15th day post-3-NP acid administration. Malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels and mitochondrial enzyme complex. Succinate dehydrogenase (SDH) were measured on the 15th day in the striatum. Systemic 3-NP acid treatment significantly reduced body weight, locomotor activity and oxidative defense. The mitochondrial enzyme activity was also significantly impaired in the striatum region in 3-NP acid-treated animals. L-theanine (100 and 200 mg/kg b.wt.) treatment significantly attenuated the impairment in behavioral, biochemical and mitochondrial enzyme activities as compared to the 3-NP acid-treated group. The results of the present study suggest that pretreatment with L-theanine significantly attenuated 3-NP induced oxidative stress and restored the decreased SOD, GSH, CAT and SDH activity. It also decreased the neuronal damage as evidenced by histopathological analysis of striatum. Based on the above study, it has been proved that L-theanine has neuroprotective activity against 3-NP induced neurotoxicity.

Water associated zero maze: a novel rat test for long term traumatic re-experiencing

Often, freezing and startle behaviors in the context of a previously experienced stress are taken as an indication of post-traumatic stress disorder (PTSD)-like symptoms in rats. However, PTSD is characterized by large individual variations of symptoms. In order to take into consideration the complex and long term distinctive variations in effects of trauma exposure additional behavioral measures are required. The current study used a novel behavioral test, the water associated zero maze (WAZM). This test was planned to enable a formation of an association between the context of the maze and an underwater trauma (UWT) or swim stress in order to examine the impact of exposure to the context which immediately precedes a stressful or a traumatic experience on rat's complex behavior. Rats were exposed to the WAZM and immediately after to an UWT or short swim. One month later rats were re-exposed to the context of the WAZM while their behavior was video recorded. Furthermore, c-Fos expression in the amygdala was measured 90 min after this exposure. The results of the current study indicate that the WAZM can be used to discern behavioral changes measured a long time after the actual traumatic or stressful events. Furthermore, the behavioral changes detected were accompanied by changes of c-Fos expression in the amygdala of exposed rats. We suggest that the WAZM can be used to model traumatic memories re-experiencing in rodent models of human stress-related pathologies such as PTSD.

Targeting oxidative stress attenuates trinitrobenzene sulphonic acid induced inflammatory bowel disease like symptoms in rats: role of quercetin.

Objective:This study was aimed to investigate the beneficial effects of quercetin (QCT) against trinitrobenzene sulfonic acid (TNBS) induced clinical, morphological, and biochemical alterations in rats.Materials and Methods:Colitis in rats was induced by administration of TNBS (25 mg dissolved in 0.25 ml of 30% ethanol) 8 cm into the rectum of the rat using a catheter. The animals were divided into six experimental groups (n = 6); naive (saline only without TNBS administration), control (saline + TNBS), standard (sulfasalazine 25 mg/kg + TNBS), QCT (25) (QCT 25 mg/kg + TNBS), QCT (50) (QCT 50 mg/kg + TNBS), QCT (100) (QCT 100 mg/kg + TNBS). Sulfasalazine (25 mg/kg) and QCT (25, 50 and 100 mg/kg) were administered per oral for 11 days and the colonic damage was evaluated in terms of macroscopical (body weight, stool consistency, rectal bleeding, and ulcer index) and biochemical parameters (myeloperoxidase activity, lipid peroxidation, nitrite, and glutathione).Results:Treatment with QCT (50, 100 mg/kg) for 10 days following TNBS administration significantly attenuated the clinical, morphological, and biochemical alterations induced by TNBS, whereas it was found to be not effective at its lower dose (25 mg/kg) throughout the experimental protocol.Conclusion:QCT attenuates the clinical, morphological and biochemical alterations induced by TNBS possibly via its antioxidant mechanism.

Minocycline modulates neuroprotective effect of hesperidin against quinolinic acid induced Huntington's disease like symptoms in rats: Behavioral, biochemical, cellular and histological evidences

Emerging evidences indicate hesperidin, a citrus flavanone, attenuates neurodegenerative processes and related complications. Besides its anti-oxidant properties, the other probable mechanisms which underpin its neuroprotective potential are still not clear. In light of emerging role of flavonoids in modulating oxidative stress and neuro-inflammation, the study has been designed to explore the possible neuroprotective effect of hesperidin and its combination with minocycline (microglial inhibitor), against quinolinic acid (QA) induced Huntington's disease (HD) like symptoms in rats. Unilateral intrastriatal administration of QA (300nmol/4µl) significantly reduced body weight, impaired behavior (locomotor activity, beam balance and memory performance), caused oxidative damage (increased lipid peroxidation, nitrite concentration, depleted super oxide dismutase and reduced glutathione), demonstrated mitochondrial dysfunction (decreased Complex-I, II, III, and IV activities), increased striatal lesion volume and altered the levels of TNF-α, caspase-3 as well as BDNF expression, as compared to sham group. Meanwhile, chronic hesperidin (100mg/kg, p.o.) and minocycline (25mg/kg, p.o.) treatment for 21 days significantly attenuated the behavioral, biochemical and cellular alterations as compared to QA treated (control) animals, whereas hesperidin (50mg/kg, p.o.) treatment was found to be non-significant. However, treatment of hesperidin (50mg/kg) in combination with minocycline (25mg/kg) potentiated their neuroprotective effect, which was significant as compared to their effects per se in QA treated animals. Taken altogether, the results of the present study suggest a possible interplay of microglial modulation and anti-oxidant effect in neuroprotective potential of hesperidin against QA induced HD like symptoms in rats.

Attenuation of proinflammatory cytokines and apoptotic process by verapamil and diltiazem against quinolinic acid induced Huntington like alterations in rats

Huntington disease is a neurodegenerative disease with complex pathophysiology. Recently, role of neuroinflammation and interplay between various other cellular cascades have been suggested to be involved in pathophysiology of Huntington disease. Involvement of calcium overload mediated oxidative damage and excitotoxicity have been suggested to play a central role in quinolinic acid induced Huntington like symptoms. The present study has been carried out to investigate the neuroprotective effect of calcium channel blockers (verapamil and diltiazem) against quinolinic acid induced dysfunction in motor, biochemical and neuroinflammatory signaling in rats. Intrastriatal quinolinic acid administration leads to significant motor [locomotor (72% reduction), rotarod (55% reduction), balance beam walk performance] dysfunction coupled with the marked oxidative damage and increased neuroinflammatory markers [TNF-α (140%), IL-6 (115%), caspase-3(75%)] levels in striatum as compared to the sham treatment. Verapamil (10 and 20mg/kg), diltiazem (10 and 20mg/kg) drug treatment for 21days resulted in a significant improvement in the motor function (improvement in locomotor activity, rotarod and balance beam walk performance). Further, verapamil (10 and 20mg/kg), diltiazem (10 and 20mg/kg) treatment significantly attenuated oxidative damage, level of proinflammatory mediators (TNF-α IL-6 and caspase-3) in quinolinic acid treated animals. Results of the present study demonstrate that protective effect of these calcium channel blockers (verapamil, diltiazem) might be due to their inhibitory action on different neuroinflammatory pathways against quinolinic acid induced Huntington disease like symptoms in rats.

Protective effect of montelukast against quinolinic acid/malonic acid induced neurotoxicity: possible behavioral, biochemical, mitochondrial and tumor necrosis factor-α level alterations in rats

The present study has been designed to explore the protective effect of montelukast (leukotriene receptor antagonist) against intrastriatal quinolinic acid (QA; 300 nmol) and malonic acid (MA; 6 μmol) induced Huntington's like symptoms in rats. Quinolinic acid has been reported to induce excitotoxicity by stimulating the N-methyl- d-aspartate receptor, causing calcium overload which in turn leads to the neurodegeneration. On the other hand, MA, being a reversible inhibitor of mitochondrial enzyme complex-II, leads to energy crisis and free radical generation. Recent studies have reported the therapeutic potential of leukotriene receptor antagonists in different neurodegenerative disorders. However, their exact role is yet to be established. The present study accordingly, is an attempt to investigate the effect of montelukast against QA and MA induced behavioral, biochemical and molecular alterations in rat striatum. Oxidative stress, mitochondrial enzyme complex and tumor necrosis factor-alpha (TNF-α) were evaluated on day 21st and 14th post intrastriatal QA and MA treatment, respectively. Findings of the present study demonstrate significant alteration in the locomotor activity and motor coordination as well as oxidative burden (increased lipid peroxidation, nitrite concentration and decreased endogenous antioxidants), mitochondrial enzyme complex (I, II and IV) activities and TNF-α level, in both intrastriatal QA and MA treated animals. Further, montelukast (0.4, 0.8 mg/kg p.o.) treatment for 21 and 14 days respectively, attenuated the behavioral alterations, oxidative stress, mitochondrial dysfunction and TNF-α level in these models of Huntington's disease in a significant manner. In conclusion, the present study emphasizes the neuroprotective potential of montelukast in the therapeutic management of Huntington like symptoms.

Protective effect of lycopene against 3-nitropropionic acid-induced Huntington's-like symptoms in rats

The present study has been designed to investigate the involvement of the nitric oxide mechanism in the protective effect of lycopene against 3-nitropropionic acid-induced Huntington's disease-like symptoms in rats. The present experimental protocol design includes systemic 3-nitropropionic acid (10 mg/kg i.p) treatment for 14 days. Lycopene (2.5, 5 and 10 mg/kg) was given orally, once a day, 1 hour before 3-nitropropionic acid treatment for 14 days. Body weight and behavioral parameters (locomotor and rotarod activity) were assessed on 1st, 5th, 10th and 15th day post-3-nitropropionic acid administration. Malondialdehyde, nitrite concentration, superoxide dismutase and catalase levels were measured on the 15th day in the striatum, cortex and hippocampus. Mitochondrial enzyme complexes were also assessed in these brain areas. Systemic 3-nitropropionic acid treatment significantly reduced body weight, locomotor activity and oxidative defense. The mitochondrial enzyme activities were also significantly impaired in the examined brain regions in 3-nitropropionic acid-treated animals. Lycopene (2.5, 5 and 10 mg/kg) treatment significantly attenuated the impairment in behavioral, biochemical and mitochondrial enzyme activities as compared to the 3-nitropropionic acid treated group. L-arginine (50 mg/kg) pretreatment with a sub-effective dose of lycopene (5 mg/kg) significantly attenuated the protective effect of lycopene. Furthermore, L-NAME (10 mg/kg) pretreatment with a sub-effective dose of lycopene (5 mg/kg) for 14 days significantly potentiated the protective effect. The results of the present study suggest that the nitric oxide modulation is involved in the protective effect of lycopene against 3-NP-induced behavioral, biochemical and cellular alterations in rats.

Protective effect of hesperidin and naringin against 3-nitropropionic acid induced Huntington's like symptoms in rats: Possible role of nitric oxide

3-Nitropropionic acid (3-NP) is a well known experimental model to study Huntington's disease (HD) and associated neuropsychiatric problems. Present study has been designed to explore the protective effects of hesperidin, naringin, and their nitric oxide mechanism (if any) against 3-nitropropionic acid induced neurotoxicity in rats. Systemic 3-nitropropionic acid (10 mg/kg) treatment for 14 days in rats significantly induced HD like symptoms in rats as indicated by reduced locomotor activity, body weight, grip strength, oxidative defense and mitochondrial complex enzymes (complex-I, -II, and -IV) activities in striatum. Naringin and hesperidin pretreatment significantly attenuated behavioral alterations, oxidative stress and mitochondrial enzymes complex dysfunction in 3-NP treated group. l-Arginine (50 mg/kg) pretreatment with lower dose of hesperidin (50 mg/kg) and naringin (50 mg/kg) significantly attenuated the protective effect of hesperidin and naringin respectively. Whereas l-NAME (10 mg/kg), a non-selective NOS inhibitor pretreatment with hesperidin (50 mg/kg) and naringin (50 mg/kg) significantly potentiated their protective effect which was significant as compared to their effect per se. Study highlights the therapeutic potential of hesperidin and naringin against Huntington's like conditions and further indicates that these drugs might act through nitric oxide mechanism.