Tenofovir-silver nanoparticles conjugate ameliorates neurocognitive disorders and protects ultrastructural and cytoarchitectonic properties of the prefrontal cortex in diabetic rats

Authors

  • Sodiq Lawal Discipline of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. https://orcid.org/0000-0002-8598-4058
  • Olojede Samuel Discipline of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. https://orcid.org/0000-0002-1000-7412
  • Sheu Oluwadare Sulaiman Department of Morphology (Cell Biology) and Birbrair Laboratory, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Minas Gerais, Belo Horizonte, Brazil https://orcid.org/0000-0002-7042-1666
  • Okikioluwa Stephen Aladeyelu Discipline of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. https://orcid.org/0000-0001-7472-3656
  • Roshila Moodley School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Durban, South Africa https://orcid.org/0000-0001-7296-0519
  • Edwin C. Stephen Naidu Discipline of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. https://orcid.org/0000-0002-2691-4017
  • Carmen Olivia Rennie Discipline of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa. https://orcid.org/0000-0003-2414-6293
  • Onyemaechi Okpara Azu Department of Anatomy, School of Medicine, University of Namibia, Windhoek, Private bag, Namibia

DOI:

https://doi.org/10.17305/bjbms.2021.6699

Keywords:

Tenofovir, Prefrontal cortex, silver nanoparticles, neuroinflammation, neurological dysfunction

Abstract

Tenofovir disoproxil fumarate (TDF) is the highly recommended antiretroviral drug in human immunodeficiency virus management. Although research has shown the neurological and metabolic disorders associated with TDF administration, the effect of TDF-silver nanoparticles conjugate (TDF-AgNPs) on the disorders has not been fully elucidated. Thus, this study evaluated the neuroprotective effects of TDF-AgNPs on ultrastructural and cytoarchitectonic properties of the prefrontal cortex (PFC) in diabetic rats. Forty-two adult male Sprague-Dawley rats (250 ± 13 g) were randomly divided into non-diabetic groups (1-3) and diabetic groups (4-6), each administered distilled water (0.5 ml/100g, p.o), TDF (26.8 mg/kg/bw, p.o) or TDF-AgNPs (6.7 mg/kg, i.p). After eight weeks of administration, cognitive function, oxidative injury and tissue inflammation were evaluated. Also, PFC ultrastructure was observed using transmission electron microscopy, Nissl staining and immunohistochemistry. Diabetic rats administered TDF exhibited cognitive deficits; and increases in blood glucose, malondialdehyde and interleukin-1 beta (IL-1β) levels, which correlate with decreases in glutathione level, and superoxide dismutase (SOD) and catalase activities. Furthermore, loss of PFC astrocytes and neuronal organelles was observed. Conversely, TDF-AgNPs administration to diabetic rats improved cognitive deficits; and increased glutathione, SOD, and catalase, but reduced PFC malondialdehyde and IL-1β concentrations. Notably, TDF-AgNPs prevented loss of PFC neurons and astrocytic cells, and morphology aberration of neuronal organelles. This study suggests that TDF-AgNPs attenuated cognitive deficits via silver nanoparticles' antioxidant and anti-inflammatory properties, preventing the loss of PFC astrocytes and neurons. The TDF-AgNPs may be utilized to ameliorate the neurological dysfunction caused by prolonged TDF administration.

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Author Biographies

Olojede Samuel, Discipline of Clinical Anatomy, School of Laboratory Medicine and Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.

PhD candidate, Discipline of Clinical Anatomy

Roshila Moodley, School of Chemistry and Physics, University of KwaZulu-Natal, Westville Campus, Durban, South Africa

School of Chemistry and Physics

Tenofovir-silver nanoparticles conjugate ameliorates neurocognitive disorders and protects ultrastructural and cytoarchitectonic properties of the prefrontal cortex  in diabetic rats

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Published

2022-02-05

How to Cite

1.
Lawal S, Olojede SO, Sulaiman SO, Aladeyelu OS, Moodley R, Naidu ECS, Rennie CO, Azu OO. Tenofovir-silver nanoparticles conjugate ameliorates neurocognitive disorders and protects ultrastructural and cytoarchitectonic properties of the prefrontal cortex in diabetic rats. Bosn J of Basic Med Sci [Internet]. 2022Feb.5 [cited 2022Jul.4];. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/6699

Issue

Section

Pharmacology