Bharat Institute of Technology

Meerut, India

Bharat Institute of Technology

Meerut, India
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Gupta S.,Bharat Institute of Technology | Sharma B.,Bharat Institute of Technology
European Journal of Pharmacology | Year: 2014

Sub-acute brain ischemia is a risk factor for the development of vascular dementia (VaD). Sub-acute brain ischemia induced VaD, participates in a negative role in impaired cognition. Imidazoline receptors are widely expressed in the central nervous system. But the role of I1-imidazoline and α2-adrenoceptors in VaD are still unknown. The present study has been designed to investigate the role of selective I1-imidazoline receptor modulator; moxonidine as well as α2-adrenoceptor modulator; clonidine in sub-acute brain ischemia induced VaD in mice (n=8). Permanent bilateral common carotid arteries ligation (2VO) technique was used to induce sub-acute brain ischemia in mice. Assessment of spatial learning and memory was done by using Morris water maze. Brain damage was assessed as percent infarct, using TTC staining of brain coronal sections. Oxidative stress was assessed by estimating brain malondialdehyde (MDA), catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD). Cholinergic status was assessed by brain acetylcholinesterase (AChE) activity. 2VO animals have shown significant reduction in learning and memory as well as brain CAT, GSH and SOD, with significant increase in brain infarct size, MDA and AChE activity. Whereas, administration of moxonidine and clonidine significantly attenuated 2VO induced learning and memory deficits, brain damage, brain oxidative stress and higher AChE activity. It may be concluded that 2VO induced sub-acute brain ischemia has elicited dementia, which was attenuated by moxonidine and clonidine. Thus, modulators of I1-imidazoline receptors may be explored further for their benefits in sub-acute brain ischemia induced vascular dementia. © 2013 Elsevier B.V.


Sharma B.,Bharat Institute of Technology | Sharma P.M.,Bharat Institute of Technology
Toxicology and Applied Pharmacology | Year: 2013

Arsenic toxicity has been reported to damage all the major organs including the brain and vasculature. Dementia including Alzheimer's disease (AD) and vascular dementia (VaD) are posing greater risk to the world population as it is now increasing at a faster rate. We have investigated the role of sodium butyrate, a selective histone deacetylase (HDAC) inhibitor and aminoguanidine, a selective inducible nitric oxide synthase (iNOS) inhibitor in pharmacological interdiction of arsenic toxicity induced vascular endothelial dysfunction and dementia in rats. Arsenic toxicity was done by administering arsenic drinking water to rats. Morris water-maze (MWM) test was used for assessment of learning and memory. Endothelial function was assessed using student physiograph. Oxidative stress (aortic superoxide anion, serum and brain thiobarbituric acid reactive species, brain glutathione) and nitric oxide levels (serum nitrite/nitrate) were also measured. Arsenic treated rats have shown impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate & brain GSH levels along with increase in serum & brain TBARS. Sodium butyrate as well as aminoguanidine significantly convalesce arsenic induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that arsenic induces endothelial dysfunction and dementia, whereas, sodium butyrate, a HDAC inhibitor as well as aminoguanidine, a selective iNOS inhibitor may be considered as potential agents for the management of arsenic induced endothelial dysfunction and dementia. © 2013 Elsevier Inc.


Kumar H.,Bharat Institute of Technology | Sharma B.,Amity University | Sharma B.,Conscience Research
Brain Research Bulletin | Year: 2016

Autism spectrum disorder (ASD) is a neurodevelopmental disorder, commonly characterized by altered social behavior, communication, biochemistry and pathological conditions. One percent of the worldwide population suffers from autism and males suffer more than females. NMDA receptors have the important role in neurodevelopment, neuropsychiatric and neurodegenerative disorders. This study has been designed to investigate the role of memantine, a NMDA receptor modulator, in prenatal valproic acid-induced autism in rats. Animals with prenatal valproic acid have shown the reduction in social interaction (three-chamber social behavior apparatus), spontaneous alternation (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (both in prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, prenatal valproic acid-treated animals have shown an increase in locomotion (actophotometer), anxiety (elevated plus maze), brain oxidative stress (thiobarbituric acid reactive species, glutathione, catalase), nitrosative stress (nitrite/nitrate), inflammation (both in brain and ileum myeloperoxidase activity), calcium and blood-brain barrier permeability. Treatment with memantine has significantly attenuated prenatal valproic acid-induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, memantine has also attenuated the prenatal valproic acid-induced increase in locomotion, anxiety, brain oxidative and nitrosative stress, inflammation, calcium and blood-brain barrier permeability. Thus, it may be concluded that prenatal valproic acid has induced autistic behavior, biochemistry and blood-brain barrier impairment in animals, which were significantly attenuated by memantine. NMDA receptor modulators like memantine should be explored further for the therapeutic benefits in autism. © 2016 Elsevier Inc.


Singha P.,Bharat Institute of Technology | Sharma B.,Amity University
Current Neurovascular Research | Year: 2016

Hypertension has been reported to induce cognitive decline and dementia of vascular origin. Serotonin- norepinephrine reuptake transporters take part in the control of inflammation, cognitive functions, motivational acts and deterioration of neurons. This study was carried out to examine the effect of venlafaxine; a specific serotonin-norepinephrine reuptake inhibitor (SNRI), in two-kidney-one-clip-2K1C (renovascular hypertension) provoked vascular dementia (VaD) in albino rats. 2K1C technique was performed to provoke renovascular-hypertension in adult male albino Wistar rats. Learning and memory were assessed by using the elevated plus maze and Morris water maze. Mean arterial blood pressure- MABP, as well as endothelial function, were assessed by means of BIOPAC system. Serum nitrosative stress (nitrite/ nitrate), aortic superoxide anion, brain oxidative stress, inflammation, cholinergic dysfunction and brain damage (2,3,5- Triphenylterazolium chloride staining) were also assessed. 2K1C has increased MABP, endothelial dysfunction as well as learning and memory impairments. 2K1C method has increased serum nitrosative stress (reduced nitrite/nitrate level), oxidative stress (increased brain thiobarbituric acid reactive species and aortic superoxide anion content along with decreased levels of brain superoxide dismutase, glutathione, and catalase), brain inflammation (increased myeloperoxidase), cholinergic dysfunction (increased acetylcholinesterase activity) and brain damage. Treatment with venlafaxine considerably attenuated renovascular-hypertension induced cognition impairment, endothelial dysfunction, serum nitrosative stress, brain and aortic oxidative stress, cholinergic function, inflammation as well as cerebral damage. The finding of this study indicates that specific modulation of the serotonin-norepinephrine transporter perhaps regarded as potential interventions for the management of renovascular hypertension provoked VaD. © 2016 Bentham Science Publishers.


Singh P.,Bharat Institute of Technology | Sharma B.,Amity University | Sharma B.,Conscience Research
Current Neurovascular Research | Year: 2016

Chronic cerebral hypoperfusion (CCH) is a general pathophysiological condition occurring in vascular dementia (VaD) associated with negative impact on cognitive functions. Ryanodine as well as cysteinyl leukotriene-1 receptors (RyRs and CysLT1Rs) are extensively present in the central nervous system, where they participate in regulation of cognition, motivation, inflammation and neurodegeneration. The purpose of this study is to examine the role of ruthenium red; a selective RyR blocker as well as montelukast; a specific CysLT1 antagonist in CCH induced VaD in mice. Two vessel occlusion (2VO) or permanent ligation of bilateral common carotid arteries technique was used to induce CCH in mice. Animals with bilateral carotid arteries occlusion have revealed impaired learning and memory (Morris water maze), cholinergic dysfunction (increased acetylcholinesterase activity) as well as increased brain oxidative stress (reduction in brain superoxide dismutase, glutathione and catalase with an increase in thiobarbituric acid reactive substance level), with increased brain infarct size (2,3,5-triphenylterazolium chloride staining). While, administration of ruthenium red and montelukast considerably attenuated CCH induced cognitive impairments, cholinergic dysfunction, brain oxidative stress as well as brain damage. The results suggest that bilateral carotid arteries occlusion induced CCH has brought out VaD, which was attenuated by treatment with ruthenium red and montelukast. Therefore, modulation of RyRs as well as CysLT1 receptors may provide help in conditions involving CCH such as cognitive impairment and VaD. © 2016 Bentham Science Publishers.


Sharma B.,Punjabi University | Sharma B.,Bharat Institute of Technology | Singh N.,Punjabi University
Pharmacology Biochemistry and Behavior | Year: 2013

Cognitive disorders are likely to increase over the coming years (5-10). Vascular dementia (VaD) has heterogeneous pathology and is a challenge for clinicians. Current Alzheimer's disease drugs have had limited clinical efficacy in treating VaD and none have been approved by major regulatory authorities specifically for this disease. Role of iNOS and NADPH-oxidase has been reported in various pathological conditions but there role in hypertension (Hypt) induced VaD is still unclear. This research work investigates the salutiferous effect of aminoguanidine (AG), an iNOS inhibitor and 4′-hydroxy-3′- methoxyacetophenone (HMAP), a NADPH oxidase inhibitor in Hypt induced VaD in rats. Deoxycorticosterone acetate-salt (DOCA-S) hypertension has been used for development of VaD in rats. Morris water-maze was used for testing learning and memory. Vascular system assessment was done by testing endothelial function. Mean arterial blood pressure (MABP), oxidative stress [aortic superoxide anion, serum and brain thiobarbituric acid reactive species (TBARS) and brain glutathione (GSH)], nitric oxide levels (serum nitrite/nitrate) and cholinergic activity (brain acetyl cholinesterase activity-AChE) were also measured. DOCA-S treated rats have shown increased MABP with impairment of endothelial function, learning and memory, reduction in serum nitrite/nitrate & brain GSH levels along with increase in serum & brain TBARS, and brain AChE activity. AG as well as HMAP significantly convalesce Hypt induced impairment of learning, memory, endothelial function, and alterations in various biochemical parameters. It may be concluded that AG, an iNOS inhibitor and HMAP, a NADPH-oxidase inhibitor may be considered as potential agents for the management of Hypt induced VaD. © 2012 Elsevier Inc.


Gupta S.,Bharat Institute of Technology | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research
Pharmacology Biochemistry and Behavior | Year: 2014

Huntington's disease (HD), a devastating neurodegenerative disorder, is characterized by progressive motor dysfunction, emotional disturbances, dementia, weight loss, depression. Melatonin receptors are widely expressed in the central nervous system. Vanilloids are also valuable as pharmacological tools for investigating neurobiology. This study investigates the utility of agomelatine, a dual agonist of MT1 and MT2 melatonin receptor as well as vanillin, a selective agonist of TRPV1 (vanilloid receptor) in 3-nitropropionic acid (3-NPA) induced experimental HD in rats. Locomotor activity (Actophotometer), motor coordination (Rota rod) and learning-memory (Morris water maze) were assessed. Brain striatum oxidative stress (lipid peroxidation-MDA, glutathione-GSH, superoxide dismutase-SOD and catalase-CAT), nitrosative stress (nitrite/nitrate) and mitochondrial enzyme complexes (I, II and IV) were also assessed. 3-NPA has induced weight loss, impaired locomotion, motor coordination as well as learning and memory. It has induced brain striatum oxidative as well as nitrosative stress, cholinergic dysfunction and impaired mitochondrial enzyme complexes (I, II and IV). Tetrabenazine (TBZ) was used as positive control. Treatment with agomelatine and vanillin and TBZ has significantly attenuated 3-NPA induced weight loss, impaired locomotion, motor coordination and learning-memory as well as biochemical impairments. Thus, agomelatine and vanillin exhibit protective effects against 3-NPA induced HD. It may be concluded that agomelatine and vanillin may provide benefits in HD. © 2014 Elsevier Inc.


Gupta S.,Neuropharmacology Laboratory | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research
European Journal of Pharmacology | Year: 2014

Huntingtons disease (HD), a devastating neurodegenerative disorder, is characterized by weight loss, impairment of motor function, cognitive dysfunction, neuropsychiatric disturbances and striatal damage. Phosphodiesterase-1 (PDE1) has been implicated in various neurological diseases. Mitochondrial potassium channels in the brain take part in neuroprotection. This study has been structured to investigate the role of vinpocetine, a selective PDE1 inhibitor as well as nicorandil, selective ATP sensitive potassium (KATP) channel opener in 3-nitropropionic acid (3-NP) induced HD symptoms in rats. Systemic administration of 3-NP significantly, reduced body weight, impaired locomotion, grip strength and impaired cognition. 3-NP elicited marked oxidative stress in the brain (enhanced malondialdehyde-MDA, reduced glutathione-GSH content, superoxide dismutase-SOD and catalase-CAT), elevated brain acetylcholinesterase activity and inflammation (myeloperoxidase-MPO), with marked nitrosative stress (nitrite/nitrate) in the brain. 3-NP has also induced mitochondrial dysfunction (impaired mitochondrial NADH dehydrogenase-complex I, succinate dehydrogenase-complex II and cytochrome oxidase-complex IV) activities in the striatum of the rat. Tetrabenazine was used as a positive control. Treatment with vinpocetine, nicorandil and tetrabenazine ameliorated 3-NP induced reduction in body weight, impaired locomotion, grip strength and impaired cognition. Treatment with these drugs reduced brain striatum oxidative (MDA, GSH, SOD and CAT) and nitrosative (nitrite/nitrate) stress, acetylcholinesterase activity, inflammation and mitochondrial dysfunctions. These results indicate that vinpocetine, a selective PDE1 inhibitor and nicorandil, a K ATP channel opener have attenuated 3-NP induced experimental HD. Hence, pharmacological modulation of PDE1 as well as KATP channels may be considered as potential research targets for mitigation of HD. © 2014 Elsevier B.V.


Gupta S.,Bharat Institute of Technology | Sharma B.,Bharat Institute of Technology | Sharma B.,Conscience Research
Brain Research Bulletin | Year: 2014

Huntington's disease (HD), a neurodegenerative disorder, is characterized by progressive motor dysfunction, emotional disturbances, dementia, weight loss and anxiety.The tremendous amount of research work is required to identify new pharmacological agents of therapeutic utility to combat this condition. This study investigates the effect of selective modulator of I1-imidazoline receptor (moxonidine) as well as nuclear factor kappa-B (NF-κB) (natrium diethyl dithio carbamate trihydrate-NDDCT) on 3-nitropropionic acid (3-NPA) induced experimental HD condition. 3-NPA was used to induce mitochondrial damage and associated HD symptoms in rats. Anxiety was assessed using Elevated plus maze-EPM and learning-memory was assessed using EPM and Morris water maze-MWM. Different biochemical estimations were used to assess brain striatum oxidative stress (lipid peroxide, superoxide dismutase and catalase), nitric oxide levels (nitrite/nitrate), cholinergic activity (brain striatum acetyl cholinesterase activity), and mitochondrial enzyme complex (I, II and IV) activities. 3-NPA has induced anxiety, impaired learning-memory with a reduction in body weight, locomotor activity, grip strength. It has increased brain striatum acetylcholinesterase-AChE activity, oxidative stress (lipid peroxide, nitrite/nitrate, superoxide dismutase and catalase) and impaired mitochondrial complex enzyme (I, II and IV) activities. Tetrabenazine-TBZ (monoamine storage inhibitor) was used as positive control. Treatment with moxonidine, NDDCT and TBZ significantly attenuated 3-NPA induced reduction in body weight, locomotor activity, grip strength, anxiety as well as impaired learning and memory. Administration of these agents attenuated 3-NPA induced various biochemical impairments. Therefore, modulation of I1-imidazoline receptor as well as NF-κB may be considered as potential pharmacological agents for the management of 3-NPA induced HD. © 2014 Elsevier Inc.


Patil V.M.,Bharat Institute of Technology
EXS | Year: 2012

Matrix metalloproteinases (MMPs) regulate a wide range of biological functions, but their overactivation leads to a wide array of disease processes such as rheumatoid arthritis, ostereoarthritis, tumor metastatis, multiple sclerosis, congestive heart failure, and a host of others. Therefore, the study of MMP inhibitors has evoked a great interest among scientists. As a result, different groups of compounds have been synthesized and studied for MMP inhibitions. Among them, a large number of structurally novel sulfonamide derivatives have been reported to be potential MMP inhibitors, but only a few have reached to the final stage of clinical trial. Many authors have made quantitative structure-activity relationship (QSAR) studies on them to provide the guidelines to design more potent MMP inhibitors. This article presents a comprehensive review on all such QSARs reported with critical assessment in order to provide a deeper insight into the structure-activity relationship of sulfonamides which can be used to synthesize highly potential drugs of pharmaceutical importance.

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