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   Table of Contents - Current issue
Coverpage
January-February 2018
Volume 50 | Issue 1
Page Nos. 1-46

Online since Monday, April 30, 2018

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EDITORIAL  

Specifically targeted antimicrobial peptides: A new and promising avenue in selective antimicrobial therapy Highly accessed article p. 1
Phulen Sarma, Saniya Mahendiratta, Ajay Prakash, Bikash Medhi
DOI:10.4103/ijp.IJP_218_18  
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RESEARCH ARTICLE Top

Effect of diethyldithiocarbamate in cyclophosphamide-induced nephrotoxicity: Immunohistochemical study of superoxide dismutase 1 in rat p. 4
Vaibhav G Sheth, Umashanker Navik, Krishna Prahlad Maremanda, Gopabandhu Jena
DOI:10.4103/ijp.IJP_850_16  
OBJECTIVES: To investigate the role of diethyldithiocarbamate (DEDTC) in cyclophosphamide (CP)-induced nephrotoxicity in Sprague–Dawley rat. DEDTC is a known chelating agent for copper and zinc. It is also used as a thiol protecting agent, as nuclear factor kappa-light-chain-enhancer of activated B-cells inhibitor and nitric oxide synthase inhibitor. It is also reported to inhibit superoxide dismutase (SOD) both in vitro and in vivo conditions. Considering this wide range of actions, current study investigated the role of DEDTC in CP-induced nephrotoxicity in experimental rat model. MATERIALS AND METHODS: Thirty-two male rats were randomized into four groups. Group 1, control received only saline ip; Group 2 and 4, received CP at the dose of 150 mg/kg body weight ip on the 4th day, while Group 3 and 4, received DEDTC at the dose of 250 mg/kg alternatively (fractionated dose of 1000 mg/kg). All the experimental animals were sacrificed on the 7th day and organs of interest were collected for biochemical, histopathological, DNA damage, and immunohistochemical assessments. RESULTS: DEDTC administration was found to further exacerbate the condition of CP-induced kidney damage as assessed by several biochemical and histological parameters. Further, the damage was also significantly reflected in the bladder in DEDTC-treated animals as compared to controls. SOD1 (Cu/Zn- dependent enzyme) expression was found to be decreased and this might be due to the action of DEDTC on SOD and other antioxidants. CONCLUSION: The present study indicates that DEDTC administration further exacerbated the CP-induced kidney damage in rat.
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Characterization of Rubia cordifolia L. root extract and its evaluation of cardioprotective effect in Wistar rat model p. 12
BS Chandrashekar, S Prabhakara, T Mohan, D Shabeer, Basavaraj Bhandare, M Nalini, PS Sharmila, DL Meghana, Basanth Kumar Reddy, HM Hanumantha Rao, H Sahajananda, K Anbazhagan
DOI:10.4103/ijp.IJP_418_17  
OBJECTIVES: Rubia cordifolia L. (RC) is a well-known and highly valuable medicinal plant in the Ayurvedic system. The present study involves evaluating antioxidant and cardioprotective property of RC root extract. MATERIALS AND METHODS: The characterization of RC root extract was carried out using standard phytochemical and biochemical analysis. The functional groups were analyzed by Fourier transform infrared (FTIR) spectroscopy and phytotherapeutic compounds were identified using high-resolution mass spectrometry (HR-MS). Cardioprotective activity of RC root extract was investigated against cyclophosphamide (CP; 100 mg/kg, i.p)-induced cardiotoxicity in male albino Wistar rats. RC (100, 200, and 400 mg/kg, p.o) or silymarin (100 mg/kg, p.o) was administered immediately after CP on the 1st day and the next consecutive 10 days. Biochemical and histopathological analysis was performed to observe the cardioprotective effects of RC root extract. RESULTS: Phytochemical analysis revealed the presence of secondary metabolites that include alkaloids, flavonoids, saponins, and anthraquinones in RC root extract. FTIR analysis revealed the presence of several functional groups. Based on HR-MS analysis, eight major phytotherapeutic compounds were identified in methanol root extract of RC. Biochemical analysis in CP-induced rat model administered with RC extract revealed significantly enhanced levels of antioxidant markers such as superoxide dismutase, catalase, and glutathione S-transferase. Histopathological study showed that the rat model treated with the root extract had reduced the cardiac injury. CONCLUSION: Our results have shown that the RC extract contains various antioxidant compounds with cardioprotective effect. Treatment with RC root extract could significantly protect CP-induced rats from cardiac tissue injury by restoring the antioxidant markers.
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Reduced synovial inflammation and inhibition of matrix metalloproteinases explicates anti-osteoarthritis activity of polyherbal formulations p. 22
Dhanashri R Ingale, Priya G Kulkarni, Soumya J Koppikar, Abhay M Harsulkar, Alpana S Moghe, Suresh D Jagtap
DOI:10.4103/ijp.IJP_29_17  
OBJECTIVES: Current osteoarthritis (OA) research experiences an incline toward Ayurveda to attain a complete cure without notable adverse effects. Ayurveda uses natural products, which are known to perform the multi-faceted role, a much demanding approach for OA management. However, lack of scientific evidence is a major drawback hindering their wider use. The present work investigated the anti-arthritic potential of Ashwagandharishta, Balarishta, Dashmoolarishta, and Triphala-extract to establish molecular-evidence for their clinical use. MATERIALS AND METHODS: Rabbit synoviocytes were induced using interleukin-1 beta (IL-1 β) and lipopolysaccharide (LPS) separately and were further treated with study formulations to test anti-inflammatory and anti-oxidant potential, using nitric oxide (NO) and malondialdehyde (MDA) assays. Collagenase inhibition activity was estimated with N-(3-[2-Furyl] acryloyl)-Leu-Gly-Pro-Ala (FALGPA)-substrate and gelatinase spot assays. Data were analyzed with GraphPad Prism using one-way ANOVA followed by Bonferroni's multiple comparison. RESULTS: The study formulations were effective against synovitis, oxidative-stress, and inhibiting collagenase. They caused NO reduction in selected concentrations. DA showed the maximum NO decline of 0.02 ± 0 and 0.97 ± 0.62 μM/ml with IL-1 β and LPS induction at 5 and 20 μg/ml concentrations, respectively. Estimated by FALGPA assay, increasing collagenase inhibition was observed as the function of concentration. All formulations showed a significant MDA decline, in dose-dependent manner. CONCLUSION: We assessed the anti-OA efficacy of conventionally prescribed Ayurvedic drugs using relevant biochemical assays. The studied formulations revealed potential to restrain synovitis, cartilage degeneration and to reduce oxidative stress, and the signature OA features. With established molecular authenticity, Ayurvedic drugs can offer a safer and affordable therapeutic option for OA.
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Zanthoxylum alatum ameliorates scopolamine-induced amnesia in rats: Behavioral, biochemical, and molecular evidence p. 30
Beenita Saikia, Chandana C Barua, Jadav Sarma, Prakash Haloi, Sarojini M Tamuli, Dhruba J Kalita, Arundhati Purkayastha, Achinta G Barua
DOI:10.4103/ijp.IJP_417_17  
OBJECTIVE: Hydroethanolic extract of Zanthoxylum alatum seeds (HEZA) in scopolamine-induced amnesia was investigated for memory enhancing activity. MATERIALS AND METHODS: Radial arm maze (RAM) test was performed to evaluate the behavioral activity. Rats were treated with HEZA (50, 100, and 200 mg/kg, p. o.) and tacrine (3 mg/kg. i. p.) for 14 days. Scopolamine (0.4 mg/kg) was injected i. p. into rats after 45 min of drug administration on the 14th day. The messenger RNA (mRNA)/protein profile of few markers (acetylcholinesterase [AChE], heme oxygenase-1 [HO-1], nuclear factor-kappa B [NFκB], nuclear factor erythroid 2–related factor 2 [Nrf2], protein phosphatase 2A[PP2A], Tau, brain-derived neurotrophic factor [BDNF], tropomyosin-related kinase B [TrkB], Bcl-2-associated X protein [Bax], and Caspase-3) were also measured by polymerase chain reaction (PCR) and immunoblotting assay. Brain cytokines (tumor necrosis factor alpha [TNF-α], interleukin [IL]-1 β, and IL-10) in hippocampus were evaluated using commercially available enzyme-linked immunosorbent assay kits. RESULTS: HEZA exhibited anti-amnesic activity as indicated by a significant reduction in the working memory error and reference memory error in RAM. Pretreatment with HEZA significantly down-regulated the expression of AChE, NFκB, Tau, Bax, and Caspase-3 with simultaneous up-regulation of Nrf2, HO-1, PP2A, BDNF, and TrkB genes in the hippocampal tissues similar to tacrine when compared with scopolamine-treated rats. Pretreatment with HEZA attenuated scopolamine-induced elevation of TNF-α, IL-1 β, levels in hippocampus and reversed diminished IL-10 concentrations towards normal levels in the brain. CONCLUSION: Zanthoxylum alatum seeds could probably counteract amnesia. Since its use is mainly reported as a stimulant and tonic, this novel activity could be a boon for the scientists to explore more in this direction.
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Levetiracetam use during pregnancy in women with epilepsy: Preliminary observations from a tertiary care center in Northern India p. 39
Ramandeep Bansal, Vanita Suri, Seema Chopra, Neelam Aggarwal, Pooja Sikka, Subhas Chandra Saha, Manoj Kumar Goyal, Praveen Kumar
DOI:10.4103/ijp.IJP_692_17  
INTRODUCTION: Data on efficacy and safety of levetiracetam (LEV) during pregnancy is still limited. We analyzed efficacy and safety of LEV during pregnancy in North Indian women with epilepsy (WWE) which is being presented here. PATIENTS AND METHODS: This retrospective study included 99 WWE (on treatment with a single antiepileptic drug [AED]) who were evaluated in medical-surgical disorder antenatal clinic of the department of obstetrics and gynecology at a tertiary care teaching hospital and referral center in North India. All the obstetric and fetal data as well as data pertaining to epilepsy were noted meticulously. RESULTS: In this study (n = 99), 35 women received carbamazepine, 28 received LEV, 15 received valproate (VPA), 13 received phenytoin (PHT), three each received oxcarbazepine and lamotrigine, respectively, and two received clobazam. Although the use of VPA was associated with significantly better control of seizures compared to LEV, its use was associated with higher risk of major congenital malformations (13.3%). The incidence of gestational hypertension was lower while incidence of fetal distress was significantly higher in WWE receiving PHT during pregnancy. None of the child born to pregnant women receiving LEV had any congenital malformation. CONCLUSION: LEV is a first-line AED during pregnancy. Future prospective studies using therapeutic drug monitoring during pregnancy may further help in establishing its role during pregnancy.
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DRUG WATCH Top

Is tapentadol a potential Trojan horse in the postdextropropoxyphene era in India? p. 44
Aniruddha Basu, Jayant Mahadevan, Dhruva Ithal, Sowmya Selvaraj, Prabhat Kumar Chand, Pratima Murthy
DOI:10.4103/ijp.IJP_21_17  
Tapentadol is a centrally acting opioid analgesic which has partial opioid agonistic and norepinephrine reuptake inhibitor action similar to its nearest congener and tramadol though with a relatively higher μ-affinity. It has abuse potential, is a scheduled drug, yet currently is not known to be an opioid widely misused in India. However, under the current drug abuse legislation in India, where common prescription opioids such as dextropropoxyphene have been banned, tapentadol may take the center stage of pharmaceutical opioid abuse in the near future. We present a series of two cases where the opioid use started with codeine, dextropropoxyphene, and buprenorphine but moved on to tapentadol and tramadol due to ease of access and cost. These cases highlight the potential of tapentadol in replacing dextropropoxyphene as the widespread prescription opioid of abuse and also emphasize the current controversies regarding opioid control policies in India.
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