Highly Active Antiretroviral Therapy-silver Nanoparticle Conjugate Alleviates Anxiety-like Behaviour in Streptozotocin-induced Diabetic Rats

Abstract Background: The inception of highly active antiretroviral therapy (HAART) has changed the management of human immunodeficiency virus (HIV) positive patients, and their life expectancy has improved. However, neurological complications associated with chronic HAART administration has not been fully addressed. Therefore, this study aimed to evaluate the potential benefits of silver nanoparticles (AgNPs) conjugates on the anxiogenic effects of HAART in type-2 diabetic rats. Methods: Forty-two (42) adult male Sprague-Dawley rats (250 ± 13 g) were divided into non-diabetic and diabetic groups. After induction of diabetes, non-diabetic and diabetic animals were administered either with de-ionized water (DW), HAART (98.2 mg/kg, p.o) or AgNPs +HAART (24.5 mg/kg, i. p) for 8 weeks. Thereafter, metabolic biomarkers, oxidative injury, tissue inflammation, and behavioural changes were evaluated, while the prefrontal cortex was excised for neurochemical analysis. Results: The HAART-treated diabetic rats showed a significant increase in blood glucose level, number of faecal pellets, malondialdehyde (MDA), and pro-inflammatory cytokines (TNF-α, IL-1β) while locomotion, reduced glutathione (GSH), superoxide dismutase (SOD) activity, and PFC-GFAP positive cells were significantly reduced compared with diabetic control. However, administration of AgNPs +HAART to diabetic rats significantly improved the blood glucose level, metabolic activities, SOD, GSH, PFC-GFAP positive cells while reducing MDA and anxiety-like behaviour in the open field test. Conclusion: Administration of HAART aggravates anxiety-like behaviours and promotes neurotoxic effects in the PFC of diabetic rats. However, AgNPs +HAART alleviates the 3 anxiogenic effects of HAART and preserves PFC-GFAP positive cells by reducing oxidative and neuroinflammatory injury.