Background. The application of nanomedicine to antiretroviral drug delivery holds promise in reducing the comorbidities related to long-term systemic exposure to highly active antiretroviral therapy (HAART). However, the safety of drugs loaded with silver nanoparticles has been debatable. This study is aimed at evaluating the effects of HAART-loaded silver nanoparticles (HAART-AgNPs) on the behavioural assessment, biochemical indices, morphological, and morphometric of the hippocampus in diabetic Sprague-Dawley rats. Methods. Conjugated HAART-AgNPs were characterized using FTIR spectroscopy, UV spectrophotometer, HR-TEM, SEM, and EDX for absorbance peaks, size and morphology, and elemental components. Forty-eight male SD rats ( 250 ± 13  g) were divided into nondiabetic and diabetic groups. Each group was subdivided into ( n = 8 ) A (nondiabetic+vehicle), B (nondiabetic+HAART), C (nondiabetic+HAART-AgNPs), D (diabetic+vehicle), E (diabetic+HAART), and F (diabetic+HAART-AgNPs). Morris water maze, Y-maze test, and weekly blood glucose levels were carried out. Following the last dose of 8-week treatment, the rats were anaesthetized and euthanized. Brain tissues were carefully removed and postfixed for Nissl staining histology. Results. 1.5 M concentration of HAART-AgNPs showed nanoparticle size 20.3 nm with spherical shape. HAART-AgNPs revealed 16.89% of silver and other elemental components of HAART. The diabetic control rats showed a significant increase in blood glucose, reduced spatial learning, positive hippocampal Nissl-stained cells, and a significant decrease in GSH and SOD levels. However, administration of HAART-AgNPs to diabetic rats significantly reduced blood glucose level, improved spatial learning, biochemical indices, and enhanced memory compared to diabetic control. Interestingly, diabetic HAART-AgNP-treated rats showed a significantly improved memory, increased GSH, SOD, and number of positive Nissl-stained neurons compared to diabetic-treated HAART only. Conclusion. Administration of HAART to diabetic rats aggravates the complications of diabetes and promotes neurotoxic effects on the experimental rats, while HAART-loaded silver nanoparticle (HAART-AgNP) alleviates diabetes-induced neurotoxicity.

The existence of a protective "sanctuary site" in the testis, which limits drug concentration or sequestration, has been suggested. [1][2][3] This sanctuary site is typified by the testis, an essential compartmentalized reproductive organ within the scrotum. It is encapsulated in the outermost to the innermost thick layers of connective tissue capsules, tunica vaginalis, tunica albuginea, and tunica vasculosa. 4 Septa from the tunica albuginea partition the testis into different lobules.Each of these lobules contains seminiferous tubules that are approximately 200 μm in diameter, with a total length of ~600 m that contributes to about 60 percent of the total volume of the testis. 5,6

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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Diabetes mellitus has not ceased to be on rise in spite of the continuous research on its management. Brain dysfunction associated with Diabetes mellitus especially Type II has been the great concern. The aim of this study was to investigate the effect of insulin sensitizing drug metformin and ethanolic extract of garlic on membrane bound enzymes Na + /K + ATPase, Ca 2+ ATPase and glutamate-glutamine cycle enzyme, Glutamine Synthetase activities in the hippocampus of streptozotocin-Nicotinamide induced Type II Diabetic rats. Twenty four male wistar rats weighted 120-150 g were used and divided into four groups with six rats in each group. Group A was non-diabetic (Control) and Groups B, C and D were diabetic. Group B received no treatment (DNT) while Groups C and D were treated with 1000 mg/kg of ethanolic garlic extract (EGE) and 50 mg/kg of metformin (MET) respectively orally for three weeks. All the groups were fed on standard rat chow with water ad libitum. Blood glucose was monitored weekly. Animals were sacrificed and the brains were removed and hippocampi were carefully excised and homogenate were obtained. Homogenate was analyzed for Na + /K + ATPase, Ca 2+ ATPase and Glutamine Synthetase (GS) activities. MET and EGE significantly reduced the blood glucose levels. There was a significant increase in the activities of hippocampal Na+/K + ATPase, Ca 2+ ATPase and GS in MET and