Evaluation of Hippocampal Microanatomy and Neuro-Biomarkers Following Administration of Silver Nanoparticles Conjugated with Tenofovir Disoproxil Fumarate in Experimental Diabetic Rats.

Adverse complications like metabolic disorders, neurotoxicity, and low central nervous system (CNS) penetration are associated with the long-term use of tenofovir disoproxil fumarate (TDF). Therefore, some modifications are required to enhance neurological functions using silver nanoparticles (AgNPs). This study aimed to evaluate the neuroprotective impact of silver nanoparticles (AgNPs)-conjugated TDF as AgNPs-TDF on the hippocampal microanatomy and some neuro-biomarkers of diabetic rats. Forty-two male Sprague-Dawley rats, with an average weight of 250 ± 13 g, were divided into non-diabetic and diabetic groups. They were further divided into 3 groups each (n = 7): non-diabetic control (NC), non-diabetic + TDF (NTF), and non-diabetic + TDF + silver nanoparticles (NTS), as well as diabetic control (DC), diabetic + TDF (DTF), and diabetic + TDF + silver nanoparticles (DTS). The characterization of AgNPs-TDF was assessed, and the conjugates were administered to the diabetic rats, followed by behavioral testing and biochemical, immunohistochemical, and microanatomy analyses of the hippocampus. The results showed that the administration of AgNPs-TDF significantly reduced the blood glucose level, malondialdehyde (MDA), and inflammatory biomarker concentrations in DTS compared with the DTF and DC groups. Furthermore, AgNPs-TDF administration significantly increased the levels of tissue superoxide dismutase (SOD), reduced glutathione (GSH), and insulin-like growth factor-1 in DTS compared with the DTF and DC groups. In addition, the DTS group revealed a monomorphic pattern of dark-stained neuronal nuclei similar to the control group and showed neuroprotective effects on hippocampal microanatomy compared with the DTF group. This study shows that AgNPs-TDF restores various alterations in the hippocampus and improves cognitive functions in diabetic rats.