Highly active antiretroviral therapy-silver nanoparticle conjugate interacts with neuronal and glial cells and alleviates anxiety-like behaviour in streptozotocin-induced diabetic rats

The inception of highly active antiretroviral therapy (HAART) has changed the management of human immunodeficiency virus (HIV) positive patients, with an improvement in life expectancy. However, neurological complications associated with high dosage and chronic administration of HAART have not been fully addressed. Therefore, this study evaluated the potential benefits of silver nanoparticles (AgNPs) conjugated-HAART (HAART-AgNPs) and its interaction with neuronal and glial cells in type-2 diabetic rats. Forty-two (n = 42) adult male Sprague-Dawley rats (250 ± 13 g) were divided into non-diabetic and diabetic groups. Each rat was administered with either distilled water, HAART, or HAART-AgNPs for eight weeks. After that, the prefrontal cortex (PFC) was excised for immunohistochemical, biochemical, and ultrastructural analysis. The formulated HAART-AgNPs were characterised by Ultraviolet-Visible, Transmission electron microscope, Energy Dispersive X-ray and Fourier transform infrared spectroscopy. Of the various concentrations of HAART-AgNPs, 1.5 M exhibited 20.3 nm in size and a spherical shape was used for this study. Administration of HAART-AgNPs to diabetic rats significantly decreased (p < 0.05) blood glucose level, number of faecal pellets, malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-α), Interleukin-1 beta (IL-1β) compared with HAART-treated diabetic rats. Notably, there was a significant increase (p < 0.05) in antioxidant biomarkers (SOD and GSH), improvement in PFC-glial fibrillary acid protein (PFC-GFAP) positive cells and alleviation of anxiety-like behaviour in HAART-AgNPs treated diabetic rats. These results showed that HAART-AgNPs alleviates the anxiogenic effect and neuronal toxicity aggravated by HAART exposure via the reduction of oxidative and neuroinflammatory injury as well as preserving PFC GFAP-positive cells and neuronal cytoarchitecture.