Premendu P Mathur

KIIT University, Bhubaneswar, Orissa, India

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Publications (64)113.02 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: The treatment of human immunodeficiency virus (HIV)-related tuberculosis (TB) includes combination therapy, in which antiretroviral drugs and anti-TB drugs are co-administered. The complexities associated with the treatment of dual infection by Mycobacterium tuberculosis and HIV include occurrence of drug–drug interactions, in addition to pill burden, overlapping drug toxicity, and immune reconstitution inflammatory syndrome. Drug–drug interactions can occur between these drugs toward cytochrome P450 3A4 (CYP3A4), a drug-metabolizing enzyme. A thorough understanding of these interactions can prevent occurrence of treatment failures and drug toxicity. Molecular docking studies were carried out for FDA-approved drugs, to predict binding mechanism of anti-TB drugs with CYP3A4 and to compare them with our previous studies on antiretroviral drugs, in order to infer possible occurrence of drug–drug interactions. The core regimen of anti-TB treatment viz., rifampin (RIF), isoniazid (INH), and pyrazinamide (PZA) showed similar binding mode (i.e., competitive binding) via utilizing the same binding residue, Arg212 in CYP3A4. This regimen also shared similar binding mode with antiretroviral protease inhibitors except tipranavir, nelfinavir, lopinavir, and atazanavir. Contraindicated drug interactions were not observed between non-nucleoside reverse transcriptase inhibitors, delavirdine, efavirenz, and etravirine; and anti-TB drugs, RIF, INH, and PZA. The contraindications occurring within anti-TB drugs can be negated with inhibitory effect of INH to induction effect of RIF toward CYP3A4. We evaluated the importance of Arg212 along with Ser119, Ala370, Arg372, and heme moiety for mediating oxidative metabolism of drugs. These drug interaction details were incorporated into our web server by creating a database called “CYP3A4 DDIDB” and it is open accessible from http://cyp.bicpu.edu.in.
    Medicinal Chemistry Research 02/2014; 23(2). · 1.61 Impact Factor
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    01/2014; 311(114):114-124.
  • Reviews of environmental contamination and toxicology 01/2014; 228:57-82. · 4.13 Impact Factor
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    ABSTRACT: Plasma Proteome Database (PPD; http://www.plasmaproteomedatabase.org/) was initially described in the year 2005 as a part of Human Proteome Organization’s (HUPO’s) pilot initiative on Human Plasma Proteome Project. Since then, improvements in proteomic technologies and increased throughput have led to identification of a large number of novel plasma proteins. To keep up with this increase in data, we have significantly enriched the proteomic information in PPD. This database currently contains information on 10 546 proteins detected in serum/plasma of which 3784 have been reported in two or more studies. The latest version of the database also incorporates mass spectrometry-derived data including experimentally verified proteotypic peptides used for multiple reaction monitoring assays. Other novel features include published plasma/serum concentrations for 1278 proteins along with a separate category of plasma-derived extracellular vesicle proteins. As plasma proteins have become a major thrust in the field of biomarkers, we have enabled a batch-based query designated Plasma Proteome Explorer, which will permit the users in screening a list of proteins or peptides against known plasma proteins to assess novelty of their data set. We believe that PPD will facilitate both clinical and basic research by serving as a comprehensive reference of plasma proteins in humans and accelerate biomarker discovery and translation efforts.
    Nucleic Acids Research 12/2013; · 8.28 Impact Factor
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    [show abstract] [hide abstract]
    ABSTRACT: Plasma Proteome Database (PPD; http://www.plasmaproteomedatabase.org/) was initially described in the year 2005 as a part of Human Proteome Organization's (HUPO's) pilot initiative on Human Plasma Proteome Project. Since then, improvements in proteomic technologies and increased throughput have led to identification of a large number of novel plasma proteins. To keep up with this increase in data, we have significantly enriched the proteomic information in PPD. This database currently contains information on 10 546 proteins detected in serum/plasma of which 3784 have been reported in two or more studies. The latest version of the database also incorporates mass spectrometry-derived data including experimentally verified proteotypic peptides used for multiple reaction monitoring assays. Other novel features include published plasma/serum concentrations for 1278 proteins along with a separate category of plasma-derived extracellular vesicle proteins. As plasma proteins have become a major thrust in the field of biomarkers, we have enabled a batch-based query designated Plasma Proteome Explorer, which will permit the users in screening a list of proteins or peptides against known plasma proteins to assess novelty of their data set. We believe that PPD will facilitate both clinical and basic research by serving as a comprehensive reference of plasma proteins in humans and accelerate biomarker discovery and translation efforts.
    Nucleic Acids Research 12/2013; · 8.28 Impact Factor
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    [show abstract] [hide abstract]
    ABSTRACT: Plasma Proteome Database (PPD; http://www.plasmaproteomedatabase.org/) was initially described in the year 2005 as a part of HUPO’s pilot initiative on Human Plasma Proteome Project. Since then, improvements in proteomic technologies and increased throughput have led to identification of a large number of novel plasma proteins. To keep up with this increase in data, we have significantly enriched the proteomic information in PPD. This database currently contains information on 10,546 proteins detected in serum/plasma of which 3,784 have been reported in 2 or more studies. The latest version of the database also incorporates mass spectrometry-derived data including experimentally verified proteotypic peptides used for multiple reaction monitoring assays. Other novel features include published plasma/serum concentrations for 1,278 proteins along with a separate category of plasma-derived extracellular vesicle proteins. As plasma proteins have become a major thrust in the field of biomarkers, we have enabled a batch-based query designated Plasma Proteome Explorer, which will permit the users in screening a list of proteins or peptides against known plasma proteins to assess novelty of their dataset. We believe that PPD will facilitate both clinical as well as basic research by serving as a comprehensive reference of plasma proteins in humans and accelerate biomarker discovery and translation efforts. Key words: body fluid database, selected reaction monitoring, proteomics, exosomal proteins, molecular diagnostics
    Nucleic Acids Res. In press. 11/2013;
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    ABSTRACT: Abstract Exposure to Nigerian bonny light crude oil (BLCO) in the southern part of Nigeria has been reported to be associated with reproductive toxicity, but there is paucity of information on its interference with steroidogenesis. This study investigated the influence of BLCO on testicular steroidogenesis and plasma levels of hormones from the pituitary and thyroid components of the brain-pituitary-testicular axis. Adult male Wistar rats were orally treated with BLCO dissolved in corn oil at 0, 200 and 800 mg/kg for 7 days. Immunoblot analysis revealed that BLCO exposure suppressed steroid acute regulatory protein and androgen-binding protein expression with concomitant decrease in 3β-hydroxysteroid dehydrogenase (HSD) and 17β-hydroxysteroid dehydrogenase activities. BLCO exposure significantly decreased plasma concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin and intratesticular testosterone, but elevated thyrotropin, triiodothyronine and thyroxine above the control values. The data presented herein indicate that undue exposure to BLCO has an inhibitory effect on testicular steroidogenesis. The underlying mechanisms for BLCO-induced testicular dysfunction may involve its disruptive effect on the brain-pituitary-testicular axis. These observations highlight the potential risk to public health for a population where, unfortunately, oil spillages occur frequently.
    Drug and Chemical Toxicology 10/2013; · 1.29 Impact Factor
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    ABSTRACT: Testicular steroidogenesis has significant implication in male reproductive function. Although the effects of various signalling molecules on testicular functions have been studied earlier, the influence of the plant hormone gibberellic acid (GA3 ) on steroidogenesis has not been investigated. Acute (4 h) and subacute (15 days) studies using this compound through oral administration (150 μg day(-1) ) to groups of normal and diabetic Wistar male rats were therefore carried out. Results indicate that (i) enhanced activity of steroidogenic markers 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), elevated tissue testosterone (T) content, increased steroidogenic acute regulatory protein (StAR) and androgen binding protein (ABP) levels with reduced lipid peroxidation and improved antioxidant defence in this treatment group of normal and diabetic rat testis, and (ii) elevated lipid peroxidation and diminished antioxidant defence, with insignificant change in 3β-HSD and 17β-HSD activity and testosterone level in acute treatment group of normal and diabetic rats testis, were noted. The observed increase in the activity of testicular 3β-HSD and 17β-HSD along with elevated testosterone content established GA3 as an inducer of steroidogenesis in rat.
    Andrologia 09/2013; · 1.55 Impact Factor
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    ABSTRACT: In the past few decades, there has been much concern about the adverse health effects of environmental contaminants in general and Crude Oil in particular around the Niger Delta region of Nigeria where all the crude Oil exploration is taking place. Studies have shown the repro-toxic effects of Bonny-light crude oil (BLCO). However, the insight into the mechanisms of gonadal toxicity induced by BLCO is not well known. In this study, we sought to elucidate the mechanism(s) underpinning the gonadal effects within hours of exposure to BLCO. Experimental rats were divided into five groups of four each. Animals were orally administered with a single dose of BLCO (800 mg/kg body weight) and killed at 0, 6, 12, 24, and 72 h post-treatment. The levels and time-course of induction of stress response proteins and apoptosis-related proteins like cytochorome C, caspase 3 and procaspase 9, Fas-FasL, NF-kB and TNF-α were determined to assess sequential induction of apoptosis in the rat testis. DNA damage was assessed by TUNEL assay. Administration of BLCO resulted in a significant increase in the levels of stress response proteins and apoptotis- related proteins as early as 6 h following exposure. Time-dependent elevations in the levels of the proteins were observed. The DNA damage was measured and showed time-dependent increase in the TUNEL positive cells of testicular cells. The study demonstrates induction of testicular apoptosis in adult rats following exposure to a single dose of BLCO. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.
    Environmental Toxicology 09/2013; · 2.71 Impact Factor
  • Isaac A Adedara, Premendu P Mathur, Ebenezer O Farombi
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    ABSTRACT: Abstract The present study investigated the protective role of kolaviron, a natural antioxidant biflavonoid isolated from the seed of Garcinia kola, in ethylene glycol monoethyl ether (EGEE)-induced testicular dysfunction in male rats. Adult male Wistar rats were exposed to EGEE (200mg/kg) separately or in combination with either kolaviron (100 or 200 mg/kg) or vitamin E (50mg/kg) for 14 days. Immunoblot analysis revealed that EGEE exposure alone significantly increased stress-inducible proteins levels. The increased protein expression of active caspases, Fas and Fas-L was accompanied by nuclear factor kappa B down-regulation and elevation of cytosolic cytochrome c level in EGEE-treated rats. Also, the observation from immunofluorescence staining was consistent with the increased TUNEL-positive nuclei in the testes of EGEE-treated rats. Kolaviron and vitamin E significantly inhibited induction of stress proteins and germ cell apoptosis in EGEE-treated rats. Overall, kolaviron by virtue of its antioxidant and anti-apoptotic properties prevented EGEE-induced reproductive toxicity in rats.
    Toxicology mechanisms and methods 09/2013; · 1.37 Impact Factor
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    ABSTRACT: Protein-peptide interactions, where one partner is a globular protein (domain) and the other is a flexible linear peptide, are key components of cellular processes predominantly in signaling and regulatory networks, hence are prime targets for drug design. To derive the details of the protein-peptide interaction mechanism is often a cumbersome task, though it can be made easier with the availability of specific databases and tools. The Peptide Binding Protein Database (PepBind) is a curated and searchable repository of the structures, sequences and experimental observations of 3100 protein-peptide complexes. The web interface contains a computational tool, protein inter-chain interaction (PICI), for computing several types of weak or strong interactions at the protein-peptide interaction interface and visualizing the identified interactions between residues in Jmol viewer. This initial database release focuses on providing protein-peptide interface information along with structure and sequence information for protein-peptide complexes deposited in the Protein Data Bank (PDB). Structures in PepBind are classified based on their cellular activity. More than 40% of the structures in the database are found to be involved in different regulatory pathways and nearly 20% in the immune system. These data indicate the importance of peptide-protein complexes in the regulation of cellular processes. PepBind is freely accessible at http://pepbind.bicpu.edu.in/.
    Genomics, proteomics & bioinformatics. 07/2013;
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    ABSTRACT: For non-hormonal male contraceptives that exert their effects in the testis locally instead of via the hypothalamic-pituitary-testicular axis, such as adjudin that disrupts germ cell adhesion, a major hurdle in their development is to improve their bioavailability so that they can be efficiently delivered to the seminiferous epithelium by transporting across the blood-testis barrier (BTB). If this can be done, it would widen the gap between their efficacy and general toxicity. However, Sertoli cells that constitute the BTB, peritubular myoid cells in the tunica propria, germ cells at different stages of their development, as well as endothelial cells that constitute the microvessels in the interstitium are all equipped with multiple drug transporters, most notably efflux drug transporters, such as P-glycoprotein, multidrug resistance-related protein 1 (MRP1) and breast cancer resistance protein (BCRP) that can actively prevent drugs (e.g., adjudin) from entering the seminiferous epithelium to exert their effects. Recent studies have shown that BCRP is highly expressed by endothelial cells of the microvessels in the interstitium in the testis and also peritubular myoid cells in tunica propria even though it is absent from Sertoli cells at the site of the BTB. Furthermore, BCRP is also expressed spatiotemporally by Sertoli cells and step 19 spermatids in the rat testis and stage-specifically, limiting to stage VII‒VIII of the epithelial cycle, and restricted to the apical ectoplasmic specialization [apical ES, a testis-specific F-actin-rich adherens junction (AJ)]. Interestingly, adjudin was recently shown to be capable of downregulating BCRP expression at the apical ES. In this Opinion article, we critically discuss the latest findings on BCRP; in particular, we provide some findings utilizing molecular modeling to define the interacting domains of BCRP with adjudin. Based on this information, it is hoped that the next generation of adjudin analogs to be synthesized can improve their efficacy in downregulating BCRP and perhaps other drug efflux transporters in the testis to improve their efficacy to traverse the BTB by modifying their interacting domains.
    Spermatogenesis. 04/2013; 3(2):e24993.
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    ABSTRACT: The study evaluated the protective role of kolaviron (an isolated biflavonoid from the seed of Garcinia kola) and vitamin E in carbendazim-induced reproductive dysfunction in male rats. Adult male Wistar rats were orally exposed to carbendazim (200mg/kg) singly or in combination with kolaviron (100 and 200mg/kg). Exposure to carbendazim significantly decreased the activities of superoxide dismutase and catalase but markedly increased sialic acid concentration and lipid peroxidation in the testes of rats. Western blot analysis revealed that carbendazim treatment decreased the expression of steroid acute regulatory (StAR) protein and androgen binding protein (ABP) with concomitant decrease in activities of steroidogenic enzymes. Germ cell apoptosis in carbendazim-treated rats was confirmed by TUNEL assay. However, pretreatment with kolaviron and vitamin E restored the testicular antioxidant status and steroidogenesis and decreased apoptotic nuclei to near control level in carbendazim-treated rats. Kolaviron may prove useful in combating carbendazim-induced reproductive toxicity.
    Environmental toxicology and pharmacology. 02/2013; 35(3):444-453.
  • S Dhanabalan, P P Mathur, P Latha
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    ABSTRACT: 2,3,7,8-Tetrachloro dibenzo-p-dioxin (TCDD), an endocrine-disrupting environmental pollutant, has been found to cause male reproductive toxicity. Glucocorticoids have been found to influence the metabolic pathway of TCDD. Stress, which affects the male reproductive function, is marked by an increase in the level and activity of glucocorticoids in the body. The present study was carried out to understand the effect of TCDD on testicular steroidogenesis and sperm antioxidant system under the influence of increased level of corticosterone in the body. Adult male rats were treated with either TCDD (100 ng/kg bw/ day) or corticosterone (3 mg/kg bw/day) or both for 15 days. Treatment with either TCDD or corticosterone was found to suppress the levels of steroidogenic acute regulatory protein and androgen-binding protein and reduce the activities of steroidogenic enzymes in testis while increasing oxidative stress in ventral prostate, seminal vesicles and epididymal sperm. In rats treated with both TCDD and corticosterone, the suppression of testicular steroidogenesis and increase in oxidative stress observed in ventral prostate, seminal vesicles and epididymal sperm were significant as compared to TCDD alone treated rats. The levels of Fas and FasL proteins were also increased in rats subjected to either TCDD or corticosterone treatment. In rats treated with both compounds, the increase observed in testicular levels of Fas and FasL was significant as compared to TCDD alone treated rats. Effect of TCDD on testicular steroidogenesis and antioxidant system of epididymal sperm may get enhanced under increased level of glucocorticoids in the body.
    Toxicology and Industrial Health 01/2013; · 1.56 Impact Factor
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    Journal of Cell Communication and Signaling 12/2012;
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    Dataset: Om-print
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    ABSTRACT: Steroidogenesis in testicular cells depends upon the availability of cholesterol within testicular mitochondria besides the activities of 3β-hydroxysteroid dehydrogenase (3β-HSD, 17β-hydroxysteroid dehydrogenase [17b-HSD]), and the tissue levels of steroidogenic acute regulatory protein (StAR), androgen-binding protein (ABP), and testosterone (T). Cellular cholesterol biosynthesis is regulated by endogenous oxycholesterols acting through nuclear hormone receptors. Plant oxysterols, such as 28-homobrassinolide (28-HB), available to human through diet, was shown to exhibit antihyperglycemic effect in diabetic male rat. Its role in rat testicular steroidogenesis and lipid peroxidation (LPO) was therefore assessed using normal and streptozotocin-induced diabetic male rats. Administration of 28-HB (333 µg/kg body weight) by oral gavage for 15 consecutive days to experimental rats diminished LPO, increased antioxidant enzyme, 3β-HSD and 17β-HSD activities, and elevated StAR and ABP expression and T level in rat testis. We report that 28-HB induced steroidogenesis in normal and diabetic rat testis.
    Reproductive sciences (Thousand Oaks, Calif.) 09/2012; · 2.31 Impact Factor
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    ABSTRACT: The nematode Wuchereria bancrofti and Brugia malayi are the causative agents of Lymphatic Filariasis, which is one of the leading causes of permanent and long-term disability in the world. Tubulin protein being involved in many cellular functions is a crucial drug target for nematodes. To have structural insights of this protein, a three dimensional model of B. malayi b-tubulin protein (BmBTP) was built using homology modeling. Docking study was performed on a selected set of ten anti-filarial drugs such as Albendazol, Albendazol sulfoxide, Albe-ndazol sulfone (ABZSOO), Benzimidazole, Carbofuran, Coumaphos, Diethylcarbamazine, Methiazole, Santonin, and Thiabendazole (TBZ) with BmBTP. The docking analysis revealed that Ser-138, Gly-10, and Cys-12 play the most critical role for H-bond interaction, whereas Thr-143, Gly-140, Gly-142, Gly-144, Gln-11, and Ala-9 make extensive van der Waal and hydrophobic contacts. The molecular dynamics (MD) simulation was performed using GROMACS4.0, at 3 ns in order to evaluate the overall stability of the BmBTP and anti-filarial drug complexes. The MD's trajectories depict that the complexes of the BmBTP–ligand are stable throughout the simulation except for TBZ. ABZSOO formed the best and stable complex with BmBTP, whereas remaining ligands were found to be as moderate inhibitors.
    Medicinal Chemistry Research 09/2012; 21(9):2415-2427. · 1.61 Impact Factor
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    Journal of Cell Communication and Signaling 06/2012; 6(3):169-73.
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    ABSTRACT: During the seminiferous epithelial cycle of spermatogenesis, the ectoplasmic specialization (ES, a testis-specific adherens junction, AJ, type) maintains the polarity of elongating/elongated spermatids and confers adhesion to Sertoli cells in the seminiferous epithelium, and known as the apical ES. On the other hand, the ES is also found at the Sertoli-Sertoli cell interface at the blood-testis barrier (BTB) known as basal ES, which together with the tight junction (TJ), maintains Sertoli cell polarity and adhesion, creating a functional barrier that limits paracellular transport of substances across the BTB. However, the apical and basal ES are segregated and restricted to the adluminal compartment and the BTB, respectively. During the transit of preleptotene spermatocytes across the BTB and the release of sperm at spermiation at stage VIII of the seminiferous epithelial cycle, both the apical and basal ES undergo extensive restructuring to facilitate cell movement at these sites. The regulation of these events, in particular their coordination, remains unclear. Studies in other epithelia have shown that the tubulin cytoskeleton is intimately related to cell movement, and MARK [microtubule-associated protein (MAP)/microtubule affinity-regulating kinase] family kinases are crucial regulators of tubulin cytoskeleton stability. Herein MARK4, the predominant member of the MARK protein family in the testis, was shown to be expressed by both Sertoli and germ cells. MARK4 was also detected at the apical and basal ES, displaying highly restrictive spatiotemporal expression at these sites, as well as co-localizing with markers of the apical and basal ES. The expression of MARK4 was found to be stage-specific during the epithelial cycle, structurally associating with α-tubulin and the desmosomal adaptor plakophilin-2, but not with actin-based BTB proteins occludin, β-catenin and Eps8 (epidermal growth factor receptor pathway substrate 8, an actin bundling and barbed end capping protein). More importantly, it was shown that the expression of MARK4 tightly associated with the integrity of the apical ES because a diminished expression of MARK4 associated with apical ES disruption that led to the detachment of elongating/elongated spermatids from the epithelium. These findings thus illustrate that the integrity of apical ES, an actin-based and testis-specific AJ, is dependent not only on the actin filament network, but also on the tubulin-based cytoskeleton.
    Spermatogenesis. 04/2012; 2(2):117-126.

Publication Stats

422 Citations
113.02 Total Impact Points

Institutions

  • 2014
    • KIIT University
      Bhubaneswar, Orissa, India
    • University of Buea
      • Faculty of Science
      Buea, South-West Province, Cameroon
  • 2013
    • Peking Union Medical College Hospital
      Peping, Beijing, China
    • University of Ibadan
      • Department of Biochemistry
      Ibadan, Oyo, Nigeria
  • 2006–2012
    • Pondicherry University
      • • Centre for Bioinformatics
      • • Department of Biochemistry and Molecular Biology
      • • School of Life Sciences
      Pondicherry, Union Territory of Puducherry, India
  • 1994–2012
    • Population Council
      • Center for Biomedical Research
      New York City, NY, United States
  • 2011
    • Kuvempu University
      • Department of Bio-Technology
      Shimogga, Karnātaka, India