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Journal of Basic and Clinical Physiology and Pharmacology

Editor-in-Chief: Horowitz, Michal

Editorial Board: Das, Kusal K. / Epstein, Yoram / S. Gershon MD, Elliot / Kodesh , Einat / Kohen, Ron / Lichtstein, David / Maloyan, Alina / Mechoulam, Raphael / Roth, Joachim / Schneider, Suzanne / Shohami, Esther / Sohmer, Haim / Yoshikawa, Toshikazu / Tam, Joseph

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Volume 29, Issue 1


Sildenafil, a phosphodiesterase-5 inhibitor, offers protection against carbon tetrachloride-induced hepatotoxicity in rat

Olorunfemi R. Molehin
  • Corresponding author
  • Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti. P.M.B.5363, Ado-Ekiti, Nigeria, Phone: +234 803 462 1267, E-mail:
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Anne A. Adeyanju / Stephen A. Adefegha
  • Functional Foods and Nutraceuticals Unit, Department of Biochemistry, Federal University of Technology, Akure, Nigeria
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/ Oluwasanmi O. Aina / Blessing A. Afolabi / Ayorinde O. Olowoyeye
  • Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti. P.M.B.5363, Ado-Ekiti, Nigeria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Jesutomi A. Oyediran
  • Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti. P.M.B.5363, Ado-Ekiti, Nigeria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Opeyemi R. Oladiran
  • Department of Biochemistry, Faculty of Science, Ekiti State University, Ado-Ekiti. P.M.B.5363, Ado-Ekiti, Nigeria
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2017-12-28 | DOI: https://doi.org/10.1515/jbcpp-2017-0011



Elevation of phosphodiesterase-5 (PDE5) activity converts cyclic guanosine monophosphate (cGMP) to 5′-GMP, a mechanism that could be associated with drug-mediated hepatotoxicity. This study investigated whether selective inhibition of PDE5 by sildenafil could offer protection against hepatotoxicity induced by carbon tetrachloride (CCl4).


CCl4 (0.5 mL/kg) was administered intraperitoneally to induce hepatotoxicity. The control group received normal saline. Sildenafil (5 mg, 10 mg, and 20 mg/kg, p.o.) was administered to CCl4-treated rats.


CCl4 significantly increased the serum levels of gamma glutamyl transferase (γ-GT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) and reduced total protein (TP) (p<0.05). Pretreatment with sildenafil moderately reduced ALP, AST, and ALT activities with modest increase in TP level. CCl4-induced changes in the antioxidant status of the liver were significantly improved by sildenafil, especially at the lowest dose of 5 mg/kg by elevating the levels of reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), and glutathione-S-transferase (GST) and preventing lipid peroxidation (p<0.05). Sildenafil did not significantly alter the total cholesterol and triglyceride levels. However, high-density lipoprotein (HDL) level was significantly increased by sildenafil (p<0.05).


The results from this study suggest that sildenafil, when used at low doses, may be a useful pharmacological protective agent against CCl4-induced hepatotoxicity.

Keywords: antioxidant; carbon tetrachloride; hepatotoxicity; sildenafil


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About the article

Received: 2017-01-27

Accepted: 2017-10-25

Published Online: 2017-12-28

Published in Print: 2018-01-26

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared

Employment or leadership: None declared.

Honorarium: None declared.

Conflict of interest: The funding organisation(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 29, Issue 1, Pages 29–35, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2017-0011.

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