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2018 ; 34
(3
): 221-229
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Investigating Organ Toxicity Profile of Tenofovir and Tenofovir Nanoparticle on
the Liver and Kidney: Experimental Animal Study
#MMPMID30057696
Peter AI
; Naidu EC
; Akang E
; Ogedengbe OO
; Offor U
; Rambharose S
; Kalhapure R
; Chuturgoon A
; Govender T
; Azu OO
Toxicol Res
2018[Jul]; 34
(3
): 221-229
PMID30057696
show ga
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.