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Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study

Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study...

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Autores principales: Peter, Aniekan Imo, Naidu, Edwin CS, Akang, Edidiong, Ogedengbe, Oluwatosin O, Offor, Ugochukwu, Rambharose, Sanjeev, Kalhapure, Rahul, Chuturgoon, Anil, Govender, Thirumala, Azu, Onyemaechi O
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Korean Society of Toxicology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057299/
https://www.ncbi.nlm.nih.gov/pubmed/30057696
http://dx.doi.org/10.5487/TR.2018.34.3.221
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author Peter, Aniekan Imo
Naidu, Edwin CS
Akang, Edidiong
Ogedengbe, Oluwatosin O
Offor, Ugochukwu
Rambharose, Sanjeev
Kalhapure, Rahul
Chuturgoon, Anil
Govender, Thirumala
Azu, Onyemaechi O
author_facet Peter, Aniekan Imo
Naidu, Edwin CS
Akang, Edidiong
Ogedengbe, Oluwatosin O
Offor, Ugochukwu
Rambharose, Sanjeev
Kalhapure, Rahul
Chuturgoon, Anil
Govender, Thirumala
Azu, Onyemaechi O
author_sort Peter, Aniekan Imo
collection PubMed
description Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman’s space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism.
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spelling pubmed-60572992018-07-27 Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study Peter, Aniekan Imo Naidu, Edwin CS Akang, Edidiong Ogedengbe, Oluwatosin O Offor, Ugochukwu Rambharose, Sanjeev Kalhapure, Rahul Chuturgoon, Anil Govender, Thirumala Azu, Onyemaechi O Toxicol Res Original Article Tenofovir nanoparticles are novel therapeutic intervention in human immunodeficiency virus (HIV) infection reaching the virus in their sanctuary sites. However, there has been no systemic toxicity testing of this formulation despite global concerns on the safety of nano drugs. Therefore, this study was designed to investigate the toxicity of Tenofovir nanoparticle (NTDF) on the liver and kidney using an animal model. Fifteen adult male Sprague-Dawley (SD) rats maintained at the animal house of the biomedical resources unit of the University of KwaZulu-Natal were weighed and divided into three groups. Control animals (A) were administered with normal saline (NS). The therapeutic doses of Tenofovir (TDF) and nanoparticles of Tenofovir (NTDF) were administered to group B and C and observed for signs of stress for four weeks after which animals were weighed and sacrificed. Liver and kidney were removed and fixed in formal saline, processed and stained using H/E, PAS and MT stains for light microscopy. Serum was obtained for renal function test (RFT) and liver function test (LFT). Cellular measurements and capturing were done using ImageJ and Leica software 2.0. Data were analysed using graph pad 6, p values < 0.05 were significant. We observed no signs of behavioural toxicity and no mortality during this study, however, in the kidneys, we reported mild morphological perturbations widening of Bowman’s space, and vacuolations in glomerulus and tubules of TDF and NTDF animals. Also, there was a significant elevation of glycogen deposition in NTDF and TDF animals when compared with control. In the liver, there were mild histological changes with widening of sinusoidal spaces, vacuolations in hepatocytes and elevation of glycogen deposition in TDF and NTDF administered animals. In addition to this, there were no significant differences in stereological measurements and cell count, LFT, RFT, weight changes and organo-somatic index between treatment groups and control. In conclusion, NTDF and TDF in therapeutic doses can lead to mild hepatic and renal histological damage. Further studies are needed to understand the precise genetic mechanism. Korean Society of Toxicology 2018-07 2018-07-15 /pmc/articles/PMC6057299/ /pubmed/30057696 http://dx.doi.org/10.5487/TR.2018.34.3.221 Text en Copyright © 2018 The Korean Society Of Toxicology http://creativecommons.org/licenses/by-nc/3.0/ This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Peter, Aniekan Imo
Naidu, Edwin CS
Akang, Edidiong
Ogedengbe, Oluwatosin O
Offor, Ugochukwu
Rambharose, Sanjeev
Kalhapure, Rahul
Chuturgoon, Anil
Govender, Thirumala
Azu, Onyemaechi O
Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study
title Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study
title_full Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study
title_fullStr Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study
title_full_unstemmed Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study
title_short Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on the Liver and Kidney: Experimental Animal Study
title_sort investigating organ toxicity profile of tenofovir and tenofovir nanoparticle on the liver and kidney: experimental animal study
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057299/
https://www.ncbi.nlm.nih.gov/pubmed/30057696
http://dx.doi.org/10.5487/TR.2018.34.3.221
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