Lawal Sodiq Kolawole, Olojede Samuel Oluwaseun, Dare Ayobami, Faborode Oluwaseun Samuel, Sulaiman Sheu Oluwadare, Naidu Edwin Coleridge, Rennie Carmen Olivia, Azu Onyemaechi Okpara
Discipline of Clinical Anatomy, School of Laboratory Medicine & Medical Sciences, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, 719 Umbilo Road, Durban, South Africa.
Department of Physiology, School of Laboratory Medicine & Medical Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South Africa.
IBRO Neurosci Rep. 2022 Jun 16;13:57-68. doi: 10.1016/j.ibneur.2022.06.003. eCollection 2022 Dec.
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 ( 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 ( 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.
高效抗逆转录病毒疗法（HAART）的出现改变了人类免疫缺陷病毒（HIV）阳性患者的治疗方式，患者的预期寿命有所提高。然而，与高剂量和长期服用HAART相关的神经并发症尚未得到充分解决。因此，本研究评估了银纳米颗粒（AgNPs）偶联HAART（HAART-AgNPs）的潜在益处及其与2型糖尿病大鼠神经元和神经胶质细胞的相互作用。将42只成年雄性Sprague-Dawley大鼠（250±13克）分为非糖尿病组和糖尿病组。每组大鼠分别给予蒸馏水、HAART或HAART-AgNPs，持续八周。之后，切除前额叶皮质（PFC）进行免疫组织化学、生化和超微结构分析。通过紫外可见光谱、透射电子显微镜、能量色散X射线光谱和傅里叶变换红外光谱对制备的HAART-AgNPs进行表征。在各种浓度的HAART-AgNPs中，1.5M的粒径为20.3nm，呈球形，本研究采用该浓度。与接受HAART治疗的糖尿病大鼠相比，给糖尿病大鼠施用HAART-AgNPs可显著降低血糖水平、粪便颗粒数量、丙二醛（MDA）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）。值得注意的是，接受HAART-AgNPs治疗的糖尿病大鼠的抗氧化生物标志物（超氧化物歧化酶和谷胱甘肽）显著增加，前额叶皮质胶质纤维酸性蛋白（PFC-GFAP）阳性细胞有所改善，焦虑样行为得到缓解。这些结果表明，HAART-AgNPs通过减少氧化和神经炎症损伤以及保护PFC GFAP阳性细胞和神经元细胞结构，减轻了HAART暴露所加重的焦虑效应和神经元毒性。
