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The protective effect of vildagliptin in chronic experimental cyclosporine A-induced hepatotoxicity.

Abstract

The study examined the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin, in cyclosporine (CsA)-induced hepatotoxicity. Rats were divided into 4 groups treated for 28 days: control (vehicle), vildagliptin (10 mg/kg, orally), CsA (20 mg/kg, s.c.), and CsA-vildagliptin group. Liver function was assessed by measuring serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (γGT), lactate dehydrogenase (LDH), and albumin, and histopathological changes of liver were examined. Oxidative stress markers were evaluated. Assessment of nuclear factor-kappa B (NF-κB) activity in hepatic nuclear extract, serum DPP-4, and expression of Bax and Bcl2 were also done. CsA-induced hepatotoxicity was evidenced by increase in serum levels of AST, ALT, and γGT; a decrease in serum albumin; and a significant alteration in hepatic architecture. Also, significant increase in thiobarbituric acid reactive substance (TBARS) and decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) levels, increased expression Bax proteins with deceased expression of Bcl2, and increased hepatic activity of NF-κB and serum DPP-4 level were observed upon CsA treatment. Vildagliptin significantly improved all altered parameters induced by CsA administration. Vildagliptin has the potential to protect the liver against CsA-induced hepatotoxicity by reducing oxidative stress, DPP-4 activity, apoptosis, and inflammation.

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  • Authors+Show Affiliations

    ,

    a Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, El-Madinah El-Munawarah, Saudi Arabia. b Department of Clinical Pharmacology, Faculty of Medicine, Suez Canal University, Egypt.

    a Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, El-Madinah El-Munawarah, Saudi Arabia. c Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Egypt.

    Source

    MeSH

    Adamantane
    Alanine Transaminase
    Animals
    Antioxidants
    Aspartate Aminotransferases
    Catalase
    Chemical and Drug Induced Liver Injury
    Cyclosporine
    Glutathione
    Glutathione Peroxidase
    Lipid Peroxidation
    Liver
    Male
    Nitriles
    Oxidative Stress
    Protective Agents
    Pyrrolidines
    Rats
    Rats, Sprague-Dawley
    Superoxide Dismutase
    Thiobarbituric Acid Reactive Substances
    Vildagliptin

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    26632647

    Citation

    El-Sherbeeny, Nagla A., and Manar A. Nader. "The Protective Effect of Vildagliptin in Chronic Experimental Cyclosporine A-induced Hepatotoxicity." Canadian Journal of Physiology and Pharmacology, vol. 94, no. 3, 2016, pp. 251-6.
    El-Sherbeeny NA, Nader MA. The protective effect of vildagliptin in chronic experimental cyclosporine A-induced hepatotoxicity. Can J Physiol Pharmacol. 2016;94(3):251-6.
    El-Sherbeeny, N. A., & Nader, M. A. (2016). The protective effect of vildagliptin in chronic experimental cyclosporine A-induced hepatotoxicity. Canadian Journal of Physiology and Pharmacology, 94(3), pp. 251-6. doi:10.1139/cjpp-2015-0336.
    El-Sherbeeny NA, Nader MA. The Protective Effect of Vildagliptin in Chronic Experimental Cyclosporine A-induced Hepatotoxicity. Can J Physiol Pharmacol. 2016;94(3):251-6. PubMed PMID: 26632647.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - The protective effect of vildagliptin in chronic experimental cyclosporine A-induced hepatotoxicity. AU - El-Sherbeeny,Nagla A, AU - Nader,Manar A, Y1 - 2015/08/24/ PY - 2015/12/4/entrez PY - 2015/12/4/pubmed PY - 2016/12/15/medline KW - apoptose KW - apoptosis KW - cyclosporine KW - inflammation KW - oxidative stress KW - stress oxydant KW - vildagliptin KW - vildagliptine SP - 251 EP - 6 JF - Canadian journal of physiology and pharmacology JO - Can. J. Physiol. Pharmacol. VL - 94 IS - 3 N2 - The study examined the effect of dipeptidyl peptidase-4 (DPP-4) inhibitor, vildagliptin, in cyclosporine (CsA)-induced hepatotoxicity. Rats were divided into 4 groups treated for 28 days: control (vehicle), vildagliptin (10 mg/kg, orally), CsA (20 mg/kg, s.c.), and CsA-vildagliptin group. Liver function was assessed by measuring serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyltransferase (γGT), lactate dehydrogenase (LDH), and albumin, and histopathological changes of liver were examined. Oxidative stress markers were evaluated. Assessment of nuclear factor-kappa B (NF-κB) activity in hepatic nuclear extract, serum DPP-4, and expression of Bax and Bcl2 were also done. CsA-induced hepatotoxicity was evidenced by increase in serum levels of AST, ALT, and γGT; a decrease in serum albumin; and a significant alteration in hepatic architecture. Also, significant increase in thiobarbituric acid reactive substance (TBARS) and decrease in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione (GSH) levels, increased expression Bax proteins with deceased expression of Bcl2, and increased hepatic activity of NF-κB and serum DPP-4 level were observed upon CsA treatment. Vildagliptin significantly improved all altered parameters induced by CsA administration. Vildagliptin has the potential to protect the liver against CsA-induced hepatotoxicity by reducing oxidative stress, DPP-4 activity, apoptosis, and inflammation. SN - 1205-7541 UR - https://www.unboundmedicine.com/medline/citation/26632647/The_protective_effect_of_vildagliptin_in_chronic_experimental_cyclosporine_A_induced_hepatotoxicity_ L2 - http://www.nrcresearchpress.com/doi/full/10.1139/cjpp-2015-0336?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -