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|Year : 2015 | Volume
| Issue : 7 | Page : 1-4
G. Achari Prize
|Date of Web Publication||11-Dec-2015|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. G. Achari Prize. Indian J Pharmacol 2015;47, Suppl S1:1-4
Hesperidin Improves Learning and Memory Outcomes Attenuating Oxidative Stress and Endothelial Dysfunction in Hyperhomocysteinemic Rats
Boyina Hemanth 1 , Bharadwaj Dinesh 2 , Diwan PV 1,3
1 Department of Pharmacology and Toxicology, School of Pharmacy, Anurag Group of Institutions, Hyderabad, Telangana, India, 2 Food and Drug Toxicology Research Centre, National Institute of Nutrition, ICMR, Hyderabad, Telangana, India, 3 Basic Science Research Center, KLE University, Belagavi, Karnataka, India
Objectives: The present study is aimed to evaluate ameliorative role of hesperidin (HSP) on memory deficits, endothelial dysfunction (ED) and neuropathological changes induced by hyperhomocysteinemia (Hhcy) in Wistar rats. Materials and Methods: Administration of L-methionine (1.7 gm/kg, p.o., 4 weeks and 4 days) produced Hhcy, ED leading to vascular dementia (VaD). Morris water maze and Y-maze test are used for assessing spatial learning and working memory performance of rats using video tracking system. After behavioural assessment animals were sacrificed for testing ED followed by biochemical and histopathological analysis of thoracic aorta and brain sections. Results: Hhcy produced significant rise in serum homocysteine, cholesterol along with significant reduction in serum nitrite levels. Brain thiobarbituric acid reactive species (TBARS) and acetylcholinesterase (AChE) levels were significantly increased. However, there is significant reduction in brain superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT) levels in L-methionine treated rats. HSP at 25 mg/kg and 50 mg/kg/p.o. has shown significant improvement in a dose dependent manner on Hhcy-induced cognitive impairment, ED along with significant changes in all serum and brain biochemical parameters and histopathological alterations when compared to L-methionine treated rats. Conclusion: The results indicated the protective role of HSP against Hhcy-induced ED and Vad. The mechanism of protection may be due to its multiple roles as a memory enhancer, anticholinergic, endothelial protective, antioxidant and neuroprotective.
Evaluation of Antidepressant Potential of New Molecules with Unpredictable Chronic Mild Stress Model in Rats
Pathak Priyanka, Panditrao Aditi, Biradar Anand, Dawane Jayshree, Pandit Vijaya
Department of Pharmacology, Bharati Vidyapeeth Deemed University Medical College, Pune, Maharashtra, India
Objectives: Stress is an important precipitant factor for depression. Chronic stress may alter behavioural, neurochemical and physiological responses. The problem of depression is increasing at an alarming rate and affects 36% individuals annually in India. Currently available drugs are associated with severe adverse effects and also show variable subjective therapeutic responses. Therefore there is a need of effective new drug for treatment to evaluate antidepressant potential of new molecule (SBK) with Unpredictable Chronic Mild Stress Model (UCMS) in rats. Materials and Methods: Wistar rats of either sex were allocated into 6 groups (n = 6), Group 1 - Control, Group 2 - Saline, Group 3 - SBK7, Group 4 - SBK8, Group 5 - Moclobemide, Group 6 - Fluoxetine. Baseline sucrose consumption was estimated. Group 1 was not exposed to any stress. All remaining groups were subjected to UCMS. Treatment given on 14th day and on 15th day Forced swim test performed after 1 hr of treatment. Immobility time measured for 5 minutes. Treatment continued for 1 week along with UCMS, and after 24 hours of food and water deprivation, sucrose preference test performed. Results: SBK7 showed significant (p < 0.05) decrease in immobility time compared to moclobemide. Results of SBK7 were comparable to fluoxetine. In sucrose preference test, SBK7 showed highly significant (p < 0.0001) increase compared to moclobemide. SBK8 also significantly (p < 0.01) increased preference compared to moclobemide. Conclusion: SBK7 & 8 appear to be effective in reducing chronic stress and SBK7 has more antidepressant potential than SBK8.
Comparative Study of Efficacy in Combination Therapy of Methotrexate with Hydroxychloroquine or Sulfasalazine in Rheumatoid Arthritis Patients in Kumaon Region
Bharat Suyash, Srivastava Bhavana, Singh Paramjeet, Bhardwaj Reena, Gaur Sanjay, Ahuja Siddharth
Department of Pharmacology, Government Medical College, Haldwani, Uttarakhand, India
Objectives: To compare the efficacy of combination therapy of methotrexate (MTX) and hydroxychloroquine (HCQ) with MTX and sulfasalazine (SSZ) in rheumatoid arthritis (RA) patients of Kumaon region. Materials and Methods: RA patients (n-100) of age group in between 18-60 years, a definite rheumatoid arthritis patients based on 2010 ACR/EULAR CRITERIA, presenting to the medicine OPD with Disease Activity Score 28 (DAS 28) Score >3.2 were randomized to receive 1 of the 2 treatment combinations in this study. HCQ was given at a dosage of 200 mg twice a day. The dosage of MTX given was 10 mg/week to 20 mg/week. And, the dosage of SSZ was 500 mg - 1 gm twice a day. The primary end point of the study was based on EULAR DAS 28 response criteria at the end of study period. Results: The mean values of DAS 28 score shows statistical significant decline within the group in every follow-up and during 2nd and 3rd follow-ups DAS 28 score between 2 groups shows statistical significant difference. At the end of study period (6 months) the difference between 2 study groups was not statistically significant. According to EULAR RESPONSE CRITERIA, 26 patient from group 1st and 27 patient from group 2nd shows good response. Conclusion: The combination of MTX and SSZ is well-tolerated, and its efficacy is comparable to that of the double combination of MTX and HCQ. Combination of MTX and SSZ however shows rapid decrease in disease activity as compared to combination of MTX and HCQ.
Evaluation of Neuroprotective Potential of Noscapine in Focal Cerebral Ischemia: Reperfusion Injury
Kawadkar Manisha, Saxena Vidhu, Dhote VV
Department of Pharmacology, Faculty of Pharmacy, VNS Group of Institutions, Bhopal, Madhya Pradesh, India
Objectives: Stroke and ensuing reperfusion injury is a major source of disability and presents the vital research area with high unmet medical needs. The objective of study was to investigate the neuroprotective potential of Noscapine on cerebral reperfusion injury in rats. Materials and Methods: Animals were randomly grouped as sham operated control group, vehicle treated reperfusion injury (I/R) control group, noscapine treated group (5 mg/kg) and noscapine treated groups (10 mg/kg). Focal cerebral ischemia was produced by middle cerebral artery occlusion for 2 h and reopening for 22 h. Effect of Noscapine on neurological deficit, cerebral infarction and brain swelling, oxidative stress biomarkers, BBB permeability and histological changes were assessed. The data of all experiments were analyzed using one way analysis of variance (ANOVA) followed by Tukey's test. Results: Treatment with noscapine showed significant (P < 0.001) reduction in both infarct volume and brain swelling. The neurological deficit was markedly reduced; noscapine significantly restored the SOD, GSH levels and decreased MDA levels at dose of 10 mg/kg. Cellular damages were restored to normal cell structure as observed in histopathological examination of treated animals at dose of 10 mg/kg as compared to 5 mg/kg. Conclusion: The neuroprotective effect of administration of noscapine could be attributed to the antioxidant and free radical scavenging property and the propensity to modulate neurodegeneration-induced oxidative impairments in the brain and can be effectively employed as a neuroprotective adjuvant to abrogate oxidative stress during the ischemic injury at 10 mg/kg. The results also showed that noscapine is able to attenuate I/R-induced brain edema by interfering in tight junction protein degradation, thereby enhancing the BBB integrity. Further characterization is required and studies are designed.
Effects of Selective Imidazolin-1 Receptor Agonists Versus Dihydropyridine-calcium Channel Blockers on Insulin Resistance in Patients of Hypertension: A Meta-analysis of RCTs
Sharanabasayyaswamy Hiremath, Priya G
Department of Pharmacology, SDM Medical College, Dharwad, Karnataka, India
0Objectives: Co-existence of insulin resistance in hypertensive patients is associated with the higher risk for development of type 2 diabetes mellitus and hence highlights the need for selecting an anti-hypertensive with beneficial effect against insulin resistance. Present study aims at analyzing the efficacies of selective imidazolin-1 (I1) receptor agonists vs dihydropyridines (DHPs) on blood pressure, indicators of insulin resistance and plasma lipids concentration. Materials and Methods: After electronic data search in PUBMED, Cochrane library and EMBASE, total four RCTs were eligible and included in analysis. Two studies used moxonidine (0.2 mg/0.4 mg), other two used rilmenidine (1 mg/2 mg) as selective I1-agonists and among DHPs amlodipine (5 mg/10 mg) was used in three studies and isradipine (5 mg/10 mg) in one. Results: Both at the end of short-term (≈3 months) and six months treatment, significant differences observed in patients treated with DHPs vs I1-agonists were decrease in SBP (Mean Difference (MD) = -2.68 mmHg; 95% CI: -1.27, -4.09), DBP (MD = -2.37 mm Hg; 95% CI: -1.39, -3.36). Significant differences of decrease in fasting serum insulin level (MD = -2.63 mU/L; 95% CI: -4.66, -0.60) and HOMA index for insulin resistance (MD = -1.14, 95% CI: -1.48, -0.80) observed in patients treated with I1-agonists compared to DHPs at short-term were not seen at the end of six months. Effects of both groups on plasma lipid levels were inconclusive. Conclusion: Efficacy of I1-agonists against indicators of insulin resistance appears to be better than DHPs, while DHPs have better effect on the amount of decrease in SBP & DBP.
Evaluation of Antiepileptic Effect of S-adenosyl Methionine and its Role in Memory Impairment in Pentylenetetrazole-induced Kindling Model in Rats
Dhediya RM, Joshi SS, Gajbhiye SV, Jalgaonkar SV, Biswas M
Department of Pharmacology and Therapeutics, Seth GSMC and KEM Hospital, Parel, Mumbai, Maharashtra, India
Objective : Epilepsy is the third most common cause of neurological disability worldwide. Despite the introduction of many second generation antiepileptic drugs in the past 20 years, around 30% of patients with epilepsy remain refractory to available treatment. Also available antiepileptic drugs (AEDs) have the potential to exert detrimental effects on cognitive function and therefore compromise patient wellbeing. S-adenosyl methionine may potential antiepileptic and memory enhancing property due to its involvement in trans-methylation reaction. The present study was designed to evaluate antiepileptic effect of S-adenosyl methionine and its role in memory impairment in pentylenetetrazole (PTZ)-induced kindling model in rats. Materials and Methods: Antiepileptic effect of SAM, 2 doses (50 and 100 mg/kg) was tested by evaluating seizure severity score and seizure latency in pentelenetetrazole-induced kindling model in rats. At the end of study, spatial memory was evaluated in elevated plus maze test and animals were sacrificed for estimation of oxidative stress markers in brain tissue homogenate. Results: Higher dose of SAM (100 mg/kg) exhibited increased in seizure latency and decrease in seizure severity score, suggesting its antiepileptic activity in PTZ-induced kindling model. Also, administration of SAM (50 and 100 mg/kg) showed increased in transfer latency in EPM test as compared to vehicle control group (p < 0.0001). Biochemical analysis of rat brain tissue revealed that malondialdehyde (MDA) was decreased (P < 0.0001) and reduced glutathione (GSH) was increased (P < 0.0001) as compared to vehicle control group. Conclusion: The results demonstrated that S-adenosyl methionine exerts antiepileptic, memory enhancing and antioxidant property in pentyleneterazole-induced kindling model of epilepsy.
Evaluation of Effect of Minocycline on Alcohol Relapse Using Experimental Models
Petare AU, Gajbhiye SV, Tripathi RK
Department of Pharmacology and Therapeutics, Seth GSMC and KEM Hospital, Parel, Mumbai, Maharashtra, India
Objectives: Evaluation of minocycline on experimental models of alcohol relapse; extinction & reinstatement induced by alcohol in conditioned place preference (CPP) paradigm and alcohol deprivation effect (ADE). Settings and Design: Neuropharmacology, Department of Pharmacology & Therapeutics, KEM Hospital. Materials and Methods: CPP standardized and performed according to an unbiased procedure. It consisted 6 phases - adaptation (Day 1), pre-conditioning (Day 2), conditioning with ethanol (Day 3, 5, 7, 9) or saline (Day 4, 6, 8, 10), post-conditioning (Day 11), extinction phase (Day 12-16) & reinstatement phase (Day 17). For ADE model rats were continuously offered alcohol (10% v/v, in water) and water for 4 consecutive weeks in two bottled choice paradigm. Groups for both the models consisted of vehicle control, disease control, naltrexone and minocycline group. Statistical Analysis Used: Paired-t test used for within group and repeated measure analysis of variance for intergroup analysis, post hoc Tukey test applied, p < 0.05. Results: Study result show in CPP model minocycline (10 and 30 mg/kg) (p value < 0.001 compared to vehicle control) blocked reinstatement of extinguished CPP. Reinstatement effect also blocked by pretreatment with naltrexone (p value < 0.001 Vs vehicle control). In the second model of ADE acute administration of minocycline (7, 21 and 35 mg/kg, i.p.) suppressed alcohol consumption (p value < 0.05 versus vehicle control) during the first hour of re-access to alcohol after 14-day of deprivation following 4 week exposure. Conclusion: The results suggest that minocycline may have a role in attenuating the rewarding property of alcohol & may represent a new approach to developing additional anti-craving therapy to treat alcoholism.
Effect of Olanzapine on Mean Arterial Blood Pressure: An Experimental Study
Saha K, Mohapatra S, Agrawal R
Department of Pharmacology, V.S.S. Medical College, Burla, Sambalpur, Odisha, India
Objectives: Schizophrenia or psychosis a major group of CNS disorders which results in serious distortion of one's capacity to recognize reality, affects approximately 1% of world population. Olanzapine is an atypical antipsychotic which is efficacious in the treatment of schizophrenia. Orthostatic hypotension is commonly reported as compared to hypotension itself. Thus we propose this study to evaluate hypotensive effect of olanzapine and to delineate its probable mechanism. Materials and Methods: Adult Albino Wistar rats (200-250 mg) of either sex were grouped into six groups each containing six animals. Groups 1 received 10 ml/kg NS, groups 2, 3, 4 received olanzapine (0.5, 1.5, 5 mg/kg), groups 5, 6 received prazosin (0.5, 1.5 mg/kg) intraperitoneally and BP was measured after 0, 30, 60 & 120 minute by using non-invasive blood pressure (NIBP) measurement method. Results: Administration of low dose of olanzapine caused no significant change in blood pressure but in higher doses (1.5, 5 mg/kg) there was significant fall in blood pressure. These effects were similar to prazosin 0.5 and 1.5 mg/kg. Conclusion: Olanzapine in human dose equivalent (1.5 & 5 mg/kg) produces significant fall in BP in rats which is similar to that seen with prazosin.
Comparative Evaluation of Analgesic Activity of SSRIs and Atypical Antidepressants: An Experimental Study
Agrawal R, Mohapatra S, Saha K
Department of Pharmacology, V.S.S. Medical College, Burla, Sambalpur, Odisha, India
Objectives: To evaluate the antinociceptive/analgesic action of selective serotonin reuptake inhibitors (SSRIs; fluoxetine, escitalopram) and atypical antidepressant (mirtazapine) and to delineate their probable mechanism. Materials and Methods: Adult Wistar albino rats were grouped as control (normal saline), SSRI (fluoxetine, escitalopram), atypical antidepressant (mirtazapine) & standard (morphine). Different doses of fluoxetine, escitalopram, mirtazapine & morphine were administered intraperitoneally in order to evaluate their sub analgesic doses using tail flick analgesiometer method to pretested sensitive rats. Tail flick latencies were obtained at 0, 30, 60, 90 and 120 min after drug administration. Results: In our study normal saline which was used as negative control did not produce any change in tail flick latency at any time of observation. Fluoxetine in doses of 5 and 10 mg produced significant increase in tail flick latency at all times of observation while the 2 mg did not show any change. Escitalopram failed to produce any change to tail flick latency at any time of observation. Mirtazapine at both the higher doses increase tail flick latency at all time of observation while lower dose produce no effects. Conclusion: The SSRIs like fluoxetine and antidepressant mirtazapine possess significant antinociceptive activity whereas escitalopram does not. However these need to be further prove in other animal model and in clinical studies.
Efficacy and Safety Evaluation of Flupirtine Versus Lornoxicam as Analgesics in Sub-acute Low Back-ache: A Single-blind Randomised Controlled Trial
Dharma Rao Uppada, Usha Kiran P, Surendra Kumar G, Mallikarjuna Rao I, Siva Prasad KV, Nageswara Rao Y
Department of Pharmacology, Rangaraya Medical College, Kakinada, Andhra Pradesh, India
Objectives: Non-steroidal anti-inflammatory drugs (NSAIDs) forms the mainstay of the treatment of low back-ache (LBA). NSAIDs treatment on long term basis have adverse effects and contraindications on certain groups of patients owing to their mechanism of action, i.e., inhibition of COX enzyme. Hence there is need for development of drugs which act by different mechanisms. Flupirtine is centrally acting analgesic with neuronal potassium (Kv7) channel opening property. Lornoxicam is a newer NSAID which is a nonspecific COX inhibitor. To compare the safety and efficacy of oral flupirtine and oral lornoxicam in chronic LBA patients as analgesic drugs. Materials and Methods: Study is a single blinded prospective clinical trial for short duration of 5 days conducted in a tertiary care hospital, Kakinada. A total of 74 (33 male/41 female) patients assigned to two treatment groups (flupirtine, n = 38; lornoxicam, n = 36). Numerical rating scale (NRS-11) and Visual Analogue Scale (VAS-100 mm) are used as pain intensity rating scales. Results: The pain intensity reduction was 4.14 ± 2.7 on NRS-11 scale and 45.4 ± 26 mm on VAS-100 mm scale in flupirtine group; and the same was 3.6 ± 2.5 and 37.3 ± 25.03 respectively in lornoxicam group, which is significant on paired t-test. A total of 16 mild adverse events, seven in flupirtine group and nine in lornoxicam group occurred in study patients. Conclusion: Flupirtinehad equal analgesic efficacy to lornoxicam in the management of moderate to severe non-specific chronic low back-ache in terms of VAS-100 mm scale and NRS-11 scale. The adverse events profile in both groups are similar and are mild.