Volume 14 Supplement 3

Abstracts from the 2nd International Science Symposium on HIV and Infectious Diseases (HIV SCIENCE 2014)

Open Access

Tenofovir induced renal damage is associated with activation of NF-κB inflammatory signaling pathway and PARP overactivation

BMC Infectious Diseases201414(Suppl 3):E5

DOI: 10.1186/1471-2334-14-S3-E5

Published: 27 May 2014


Tenofovir is recommended as a first-line therapy in HIV treatment. However, its long term use is associated with proximal tubular injury and renal dysfunction. Tenofovir has been shown to target the proximal tubular mitochondria, resulting in severe mitochondrial injury and overproduction of ROS and RNS. ROS are potent stimuli for the activation of NF-κB, a key transcription factor, which is known to mediate inflammation.The NF-κB response proinflammatory genes include iNOS, COX, TNFα, and others such as PARP-1. In the present study, we investigated whether NF-κB inflammatory signaling pathway plays a role in tenofovir nephrotoxicity.


Rats were administered 2 daily doses of tenofovir (300mg/kg body weight) by gavage for 35 consecutive days, while control rats received water alone. On the 36th day, the rats were killed and the kidneys were used for the following assays. (a)NFkB protein expression by WB and immunostaining methods, mRNA expression by RT-PCR and activity by ELISA, and IkB-α protein expression and mRNA expression, (b) iNOS protein expression by WB, immunostaining methods, and mRNA expression by PCR, (c) COX-2 protein and mRNA expression, and (d) PARP-1 protein.


The results of the present study reveal that NF-κB signaling pathway is upregulated in the kidneys of rats chronically treated with tenofovir, as evidenced by a statistically significant increase in the mRNA and protein expressions of NFkB, and its target proinflammatory genes, iNOS, COX-2, TNF α and PARP-1 as compared with control.


NF-κB inflammatory signaling pathway may play a role in the pathophysiology of tenofovir nephrotoxicity.

Authors’ Affiliations

Department of Biochemistry, Christian Medical College, Bagayam
Department of Anatomy, Christian Medical College, Bagayam


© Ramamoorthy et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.