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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


CiteScore 2016: 1.01

SCImago Journal Rank (SJR) 2016: 0.349
Source Normalized Impact per Paper (SNIP) 2016: 0.495

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2191-0286
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Volume 25, Issue 4

Issues

Preclinical efficacy of melatonin in the amelioration of tenofovir nephrotoxicity by the attenuation of oxidative stress, nitrosative stress and inflammation in rats

Hemalatha Ramamoorthy / Premila Abraham / Bina Isaac
Published Online: 2014-01-27 | DOI: https://doi.org/10.1515/jbcpp-2013-0135

Abstract

Background: Nephrotoxicity is a dose-limiting side effect of long-term use of tenofovir, a reverse transcriptase inhibitor that is used for the treatment of human immunodeficiency virus (HIV) infection. Identifying an agent that prevents tenofovir disoproxil fumarate (TDF)-induced renal injury can lead to better tolerance to TDF, and a more effective treatment can be achieved in HIV infected patients. Recent studies show that oxidative stress, nitrosative stress, and inflammation play a role in TDF nephrotoxicity. The present study is aimed at investigating whether melatonin, a potent antioxidant and anti-inflammatory agent, protects against TDF nephrotoxicity in rats.

Methods: Adult male rats were used for the study. Some rats received 600 mg/kg body weight TDF by gavage for 35 days, while others received once daily 20 mg/kg body weight melatonin i.p. 2 h before TDF administration. All the rats were sacrificed on the 36th day, after overnight fast.

Results: Melatonin pretreatment protected the rats against TDF nephrotoxicity both histologically and biochemically. Biochemically, melatonin pretreatment attenuated TDF-induced renal oxidative stress, nitrosative stress, and inflammation and preserved proximal tubular function. Histologically, melatonin pretreatment prevented TDF-induced proximal tubular injury and mitochondrial injury such as swelling, disruption of cristae, and deposition of amorphous material in the matrix. It restored the lysosomal and mitochondrial numbers in the proximal tubules also.

Conclusions: Melatonin pretreatment protects rats from tenofovir-induced damage to proximal tubular mitochondria by attenuating oxidative stress, nitrosative stress, and inflammation. This suggests that it may be useful in ameliorating TDF nephrotoxicity in humans.

Keywords: inflammation; melatonin; nephrotoxicity; tenofovir

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About the article

Corresponding author: Premila Abraham, Department of Biochemistry, Christian Medical College, Bagayam, Vellore 632002, Tamil Nadu, India, Phone: +91-416-2284267, Fax: +91-416-2262788, E-mail:


Received: 2013-09-19

Accepted: 2013-12-09

Published Online: 2014-01-27

Published in Print: 2014-11-01


Citation Information: Journal of Basic and Clinical Physiology and Pharmacology, Volume 25, Issue 4, Pages 387–399, ISSN (Online) 2191-0286, ISSN (Print) 0792-6855, DOI: https://doi.org/10.1515/jbcpp-2013-0135.

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