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

Abstract

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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“…Liver sections of H&E staining did not show any of the typical signs of acute or subacute tissue injury, such as the vacuolated swelling of the cytoplasm of hepatocytes. Similarly, the kidneys presented normal tubular brush borders and intact glomeruli surrounding the Bowman's capsule, evidencing the absence of kidney injury (Figure 9) [45].…”

Effect of long-term administration of Cinnamomum cassia silver nanoparticles on organs (kidneys and liver) of Sprague-Dawley rats

“…Silver nanoparticles (AgNPs) have gained unique attention because of their attractive properties, including their high surface to volume proportions, reactant properties, and antimicrobial impact (Okafor et al, 2013) . This is particularly relevant in the health sciences as it opens new frontiers in drug synthesis and delivery needed to target some of the sanctuary sites difficult for normal therapeutic doses of drugs to penetrate (Peter et al, 2018) . However,most techniques used for the synthesis of nanoparticles (NPs) are costly and may negatively influence biological systems.…”

Acute Toxicity Effect of Artemisia Afra Plant Extracts on the Liver, Kidney, Spleen and in Vivo Antimalarial Assay on Swiss Albino Mice

“…Organs weight is an index of swelling, atrophy or hypertrophy [20]. Comparison of organ weights between control and treated groups have conventionally been used to predict the toxic effects of test material [21][22][23] and help to know if the organs were exposed to injury or not. However, in the present study, there was no significant change in organ (liver, spleen, and kidney) weights and visual gross examination of the organs of both treated mice and the controls.…”