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

doi:10.1515/jbcpp-2013-0135

Article

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 and Bina Isaac

Published/Copyright: January 27, 2014

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From the journal Journal of Basic and Clinical Physiology and Pharmacology Volume 25 Issue 4

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

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: premilaabraham@cmcvellore.ac.in

Acknowledgments

We would like to thank the Centre for Scientific and Industrial Research (CSIR), New Delhi, for the financial support. Ms. Hemalatha Ramamoorthy is a senior research fellow on the project.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

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Received: 2013-9-19

Accepted: 2013-12-9

Published Online: 2014-1-27

Published in Print: 2014-11-1

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https://doi.org/10.1515/jbcpp-2013-0135

Keywords for this article

inflammation; melatonin; nephrotoxicity; tenofovir