For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
16
views
51
references
 Top references
cited by
1
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      270
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Protective effect of melatonin against zonisamide-induced reproductive disorders in male rats

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Introduction

          Zonisamide (ZNS) is a modern antiepileptic drug (AED) that is distinguished from other AEDs by its unique structure and broad mechanistic profile. The pineal hormone melatonin is involved in the regulation of reproductive function, including the timing of the luteinizing hormone (LH) surge. The aim of the present work was to study the protective effect of melatonin against the potential suppression impact of ZNS on reproductive activity.

          Material and methods

          Ninety adult albino male rats were allocated to several groups treated with melatonin (10 mg/kg BW), ZNS (10, 20 and 50 mg/kg BW) and 10 mg/kg of melatonin plus ZNS (10, 20 or 50 mg/kg BW, respectively). Reproductive hormones (testosterone, LH and follicle-stimulating hormone (FSH)) levels were measured in animal serum. Sperm abnormalities and DNA fragmentation in testis tissues as well as expression alteration of several reproductive-related genes were analyzed.

          Results

          The results revealed that ZNS decreased the levels of serum free testosterone, LH, and FSH and expression of their encoding genes in male rats. In addition, ZNS treatment increased the sperm abnormalities and DNA fragmentation and inducible nitric oxide synthase (iNOS) in testis tissues as well as GABA level in liver tissues. However, melatonin supplementation inhibited the negative symptoms of ZNS in which it increased the levels of reproductive hormones and expression of their encoding genes in the ZNS-treated rats. Moreover, melatonin decreased the sperm abnormalities, DNA fragmentation, iNOS activity and GABA level in ZNS-treated rats.

          Conclusions

          The data obtained in this study suggest that melatonin administration confers protection against toxicity inflicted by ZNS, and support the contention that melatonin protection is achieved by its ability as a scavenger for free radicals generated by ZNS.

          Related collections

          Most cited references51

          • Record: found
          • Abstract: found
          • Article: not found

          Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p.

          John P. Brown, M. Huang, S Metzner … (2001)
          Eukaryotic cells respond to DNA damage by arresting the cell cycle and modulating gene expression to ensure efficient DNA repair. The human ATR kinase and its homolog in yeast, MEC1, play central roles in transducing the damage signal. To characterize the role of the Mec1 pathway in modulating the cellular response to DNA damage, we used DNA microarrays to observe genomic expression in Saccharomyces cerevisiae responding to two different DNA-damaging agents. We compared the genome-wide expression patterns of wild-type cells and mutants defective in Mec1 signaling, including mec1, dun1, and crt1 mutants, under normal growth conditions and in response to the methylating-agent methylmethane sulfonate (MMS) and ionizing radiation. Here, we present a comparative analysis of wild-type and mutant cells responding to these DNA-damaging agents, and identify specific features of the gene expression responses that are dependent on the Mec1 pathway. Among the hundreds of genes whose expression was affected by Mec1p, one set of genes appears to represent an MEC1-dependent expression signature of DNA damage. Other aspects of the genomic responses were independent of Mec1p, and likely independent of DNA damage, suggesting the pleiotropic effects of MMS and ionizing radiation. The complete data set as well as supplemental materials is available at http://www-genome.stanford.edu/mec1.
          Article 0 comments Cited 144 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages.

            Lisa Mayo, Rüdiger Hardeland, Russel Reiter … (2005)
            Inflammation is a complex phenomenon involving multiple cellular and molecular interactions which must be tightly regulated. Cyclooxygenase-2 (COX) is the key enzyme that catalyzes the two sequential steps in the biosynthesis of PGs from arachidonic acid. The inducible isoform of COX, namely COX-2, plays a critical role in the inflammatory response and its over-expression has been associated with several pathologies including neurodegenerative diseases and cancer. Melatonin is the main product of the pineal gland with well documented antioxidant and immuno-modulatory effects. Since the action of the indole on COX-2 has not been previously described, the goal of the present report was to test the effect of melatonin on the activities of COX-2 and inducible nitric oxide synthase (iNOS), using lipopolysaccharide (LPS)-activated RAW 264.7 macrophages as a model. Melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), prevented COX-2 activation induced by LPS, without affecting COX-1 protein levels. The structurally related compound 6-methoxy-melatonin only partially prevented the increase in COX-2 protein levels induced by the toxin. Likewise melatonin prevented iNOS activation and reduced the concentration of products from both enzymes, PGE(2) and nitric oxide. Another endogenous antioxidant like N-acetyl-cysteine (NAC) did not reduced COX-2 significantly. The current finding corroborates a role of melatonin as an anti-inflammatory agent and, for the first time, COX-2 and iNOS as molecular targets for either melatonin or its metabolites AFMK and AMK. These anti-inflammatory actions seem not to be exclusively mediated by the free radical scavenging properties of melatonin. As a consequence, the present work suggests these substances as a new class of potential anti-inflammatory agents without the classical side effects due to COX-1 inhibition.
            Article 0 comments Cited 65 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              SAS: User´S guide: Statistics

              (2002)
              Article 0 comments Cited 62 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Arch Med Sci
                Journal ID (iso-abbrev): Arch Med Sci
                Journal ID (publisher-id): AMS
                Title: Archives of Medical Science : AMS
                Publisher: Termedia Publishing House
                ISSN (Print): 1734-1922
                ISSN (Electronic): 1896-9151
                Publication date (Electronic): 05 December 2013
                Publication date (Print): 19 June 2015
                Volume: 11
                Issue: 3
                Pages: 660-669
                Affiliations
                [1 ]Cell Biology Department, National Research Centre, Dokki, Giza, Egypt
                [2 ]Department of Biological Science, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia
                Author notes
                Corresponding author: Dr. Wagdy K. B. Khalil, Cell Biology Department, Genetic Engineering and Biotechnology Division, National Research Centre (NRC), 33 El-Bohouth Street, 12622 Dokki, Giza, Egypt. Phone: +20122-7410600, Fax: +202-33370931. E-mail: wkbassaly@ 123456gmail.com , wagdykh@ 123456yahoo.com
                Article
                Publisher ID: 21908
                DOI: 10.5114/aoms.2013.39384
                PMC ID: 4495141
                SO-VID: 91548cf2-4036-4c3b-89a3-31fdcee0b7e6
                Copyright © Copyright © 2015 Termedia & Banach
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 13 April 2013
                Date revision received : 22 May 2013
                Date accepted : 18 June 2013
                Categories
                Subject: Experimental Research

                ScienceOpen disciplines: Medicine
                Keywords: zonisamide,melatonin,testosterone,luteinizing hormone,follicle-stimulating hormone,gene expression,dna damage
                Data availability:
                ScienceOpen disciplines: Medicine
                Keywords: zonisamide, melatonin, testosterone, luteinizing hormone, follicle-stimulating hormone, gene expression, dna damage

                Comments

                Comment on this article