Online citations, reference lists, and bibliographies.
← Back to Search

Investigating Organ Toxicity Profile Of Tenofovir And Tenofovir Nanoparticle On The Liver And Kidney: Experimental Animal Study

A. I. Peter, E. C. Naidu, E. Akang, O. O. Ogedengbe, Ugochukwu Ifeyinwa Offor, Sanjeev Rambharose, Rahul S. Kalhapure, A. Chuturgoon, T. Govender, O. O. Azu
Published 2018 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
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.
This paper references
Development and validation of stability indicating rp-hplc method for tenofovir solid lipid
V. M. Suvarna (2017)
10.1126/science.1193748
Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women
Q. Abdool Karim (2010)
Biocompatible, uniform, and redispersible mesoporous silica nanoparti 228 A.I. Peter et al. cles for cancer targeted drug delivery in vivo
Q. Zhang (2014)
10.1002/ADFM.201302988
Biocompatible, Uniform, and Redispersible Mesoporous Silica Nanoparticles for Cancer‐Targeted Drug Delivery In Vivo
Q. Zhang (2014)
10.4103/0253-7613.96296
Antiretroviral drugs: Critical issues and recent advances
M. Desai (2012)
10.1039/c7tx00146k
Cell to rodent: toxicological profiling of folate grafted thiomer enveloped nanoliposomes.
M. Sohail (2017)
Fact sheet -Latest statistics on the status of the AIDS epidemic
(2017)
[Antiepileptic drugs and the liver].
J. Adín (2000)
10.1038/KI.1980.181
Metabolism of drugs by the kidney.
M. Anders (1980)
10.1159/000460187
Guide for the Care and Use of Laboratory Animals
A. Rowan (1979)
10.3390/v4040488
Nanotechnology and the Treatment of HIV Infection
R. Parboosing (2012)
10.1016/j.jsps.2013.02.003
Factors affecting the development of adverse drug reactions (Review article).
M. Alomar (2014)
10.1039/C5TB00957J
Novel dendritic derivatives of unsaturated fatty acids as promising transdermal permeation enhancers for tenofovir.
Sanjeev Rambharose (2015)
10.1016/S0074-7750(03)01005-X
Prevalence and Correlates of Psychotropic Medication Use among Adults with Developmental Disabilities: 1970–2000
Maria G. Valdovinos (2003)
10.1039/C5RA16248C
Transforming linoleic acid into a nanoemulsion for enhanced activity against methicillin susceptible and resistant Staphylococcus aureus
Sandeep J. Sonawane (2015)
10.4103/0976-500X.81895
Toxicological screening
S. Parasuraman (2011)
10.1038/s41598-017-16293-6
A New Approach to Deliver Anti-cancer Nanodrugs with Reduced Off-target Toxicities and Improved Efficiency by Temporarily Blunting the Reticuloendothelial System with Intralipid
L. Liu (2017)
10.1016/j.seizure.2005.12.009
Antiepileptic drugs and liver disease
S. N. Ahmed (2006)
10.1016/J.JCRPR.2016.11.002
Computer-assisted image analysis in the diagnosis of gynaecological lesions: A quantitative and comparative investigation of haematoxylin-eosin with special dyes on tissue
F. M. Onyije (2017)
Metabolism of drugs and carcinogens by human liver enzymes.
R. Kuntzman (1966)
Markers of renal function tests
Shivaraj Gowda (2010)
Development and validation of stability indicating rp - hplc method for tenofovir solid lipid nanoparticles
V. M. Suvarna (2017)
Statistics South Africa. P0302. Midyear population estimates
(2016)
10.2217/nnm.10.1
Emerging nanotechnology approaches for HIV/AIDS treatment and prevention.
T. Mamo (2010)
10.1039/C4RA06406B
Polymeric nanocarriers for expected nanomedicine: current challenges and future prospects
Bihter Daglar (2014)
10.1126/science.1165706
The Challenge of Finding a Cure for HIV Infection
D. Richman (2009)
10.1080/01926230490465874
Relationships Between Organ Weight and Body/Brain Weight in the Rat: What Is the Best Analytical Endpoint?
S. Bailey (2004)
10.1016/j.biotechadv.2013.11.009
pH-sensitive nano-systems for drug delivery in cancer therapy.
J. Liu (2014)
10.2174/0929867321666140601162314
Toxicity of nanoparticles.
M. Zoroddu (2014)
10.1155/2015/630690
Formulation and optimization of Eudragit RS PO-tenofovir nanocarriers using Box-Behnken experimental design
Kefilwe Matlhola (2015)
10.1016/j.colsurfb.2017.03.040
Nanoemulgel using a bicephalous heterolipid as a novel approach to enhance transdermal permeation of tenofovir.
Sanjeev Rambharose (2017)
10.1021/nl102184c
Nanotechnology in drug delivery and tissue engineering: from discovery to applications.
J. Shi (2010)
10.14814/phy2.12088
Automated quantification of renal fibrosis with Sirius Red and polarization contrast microscopy
J. M. Street (2014)
Transforming lin oleic acid into a nanoemulsion for enhanced activity against methicillin susceptible and resistant Staphylococcus aureus
S. J. Sonawane (2015)
10.5487/TR.2016.32.4.317
Coconut Oil Extract Mitigates Testicular Injury Following Adjuvant Treatment with Antiretroviral Drugs
O. O. Ogedengbe (2016)
10.1038/nrd3499
Bio-inspired, bioengineered and biomimetic drug delivery carriers
Jin-Wook Yoo (2011)
Factors affecting the development of adverse drug reactions
M. J. Alomar (2014)
10.1016/j.etp.2015.07.005
Investigating the cytotoxicity of iron oxide nanoparticles in in vivo and in vitro studies.
S. Ghasempour (2015)
10.1371/journal.pmed.1001418
Life Expectancies of South African Adults Starting Antiretroviral Treatment: Collaborative Analysis of Cohort Studies
L. Johnson (2013)
10.1002/jps.22529
Formulation of tenofovir-loaded functionalized solid lipid nanoparticles intended for HIV prevention.
Dima Alukda (2011)
10.17140/HARTOJ-2-113
Why Novel Nanoparticle-based Delivery Platforms Hold Key for HIV/AIDS Treatment and Prevention?
Michael O Otieno (2015)
10.1080/10408444.2016.1181047
The effects of nanoparticles on the renal system
I. Iavicoli (2016)
10.1016/J.NANTOD.2011.10.001
Toxicology and clinical potential of nanoparticles
L. Yildirimer (2011)
10.1097/01.aids.0000210608.70762.c3
Safety and tolerability of tenofovir vaginal gel in abstinent and sexually active HIV-infected and uninfected women
K. Mayer (2006)
10.1016/S2352-3018(16)30087-X
Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015
Haidong Tim M Austin Grant Hmwe Hmwe Emmanuela Simon I Edw Wang Wolock Carter Nguyen Kyu Gakidou Hay Mills Tr (2016)
10.1293/tox.26.29
Change Trends of Organ Weight Background Data in Sprague Dawley Rats at Different Ages
Y. Piao (2013)
10.1093/ilar/ilw049
The Guide for the Care and Use of Laboratory Animals.
L. Michael (2016)



This paper is referenced by
10.1016/j.molliq.2020.114053
Application of gelatin nanoconjugates as potential internal stimuli-responsive platforms for cancer drug delivery
A. Hussain (2020)
10.1093/toxres/tfaa060
Microscopic and biochemical changes on liver and kidney of Wistar rats on combination antiretroviral therapy: the impact of naringenin and quercetin.
E. Akang (2020)
10.30466/vrf.2018.93512.2256
Crocin exerts improving effects on indomethacin-induced small intestinal ulcer by antioxidant, anti-inflammatory and anti-apoptotic mechanisms
Sadat Ghafarzadeh (2019)
10.3906/biy-1805-103
Effect of long-term administration of Cinnamomum cassia silver nanoparticles on organs (kidneys and liver) of Sprague-Dawley rats
K. Kouame (2018)
10.29235/1814-6023-2020-17-1-55-63
Асаблівасці ўльтраструктуры печані пацукоў пры ўздзеянні анты рэтравіруснага прэпарата тэнафавіра дзіcапраксіл фумарат у спалучэнні з S-адэназілметыянінам
А. Б. Астроўская (2020)
10.1016/j.colsurfb.2019.01.051
Comprehensive Toxicity Assessment of PEGylated Magnetic Nanoparticles for in vivo applications.
C. Caro (2019)
10.1097/MD.0000000000016943
Effectiveness of tenofovir and entecavir in nucleos(t)ide analogue-naive chronic hepatitis B
Mao-Bing Chen (2019)
10.3390/nano10050907
Bi-Magnetic Core-Shell CoFe2O4@MnFe2O4 Nanoparticles for In Vivo Theranostics
V. Nica (2020)
10.1016/j.ijbiomac.2019.07.154
The effect of aluminum oxide on red blood cell integrity and hemoglobin structure at nanoscale.
Sharareh Kahbasi (2019)
10.3390/jcm8122105
Maximum Glomerular Diameter and Oxford MEST-C Score in IgA Nephropathy: The Significance of Time-Series Changes in Pseudo-R2 Values in Relation to Renal Outcomes
H. Kataoka (2019)
10.3390/pharmaceutics11050197
Reverse Transcriptase Inhibitors Nanosystems Designed for Drug Stability and Controlled Delivery
F. Grande (2019)
Semantic Scholar Logo Some data provided by SemanticScholar