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.

中文翻译：

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替诺福韦-银纳米颗粒缀合物可改善糖尿病大鼠的神经认知障碍并保护前额皮质的超微结构和细胞结构特性。


富马酸替诺福韦二吡呋酯 (TDF) 是人类免疫缺陷病毒管理中强烈推荐的抗逆转录病毒药物。尽管研究表明 TDF 给药与神经和代谢紊乱有关，但 TDF-银纳米粒子缀合物 (TDF-AgNPs) 对这些疾病的影响尚未完全阐明。因此，本研究评估了 TDF-AgNPs 对糖尿病大鼠前额皮质 (PFC) 超微结构和细胞结构特性的神经保护作用。 42只成年雄性Sprague-Dawley大鼠（250±13g）随机分为非糖尿病组（1-3）和糖尿病组（4-6），每组给予蒸馏水（0.5ml/100g，po）， TDF（26.8 mg/kg/bw，口服）或 TDF-AgNP（6.7 mg/kg，腹腔注射）。给药八周后，评估认知功能、氧化损伤和组织炎症。此外，使用透射电子显微镜、尼氏染色和免疫组织化学观察 PFC 超微结构。服用 TDF 的糖尿病大鼠表现出认知缺陷；血糖、丙二醛和白细胞介素 1 β (IL-1β) 水平升高，这与谷胱甘肽水平、超氧化物歧化酶 (SOD) 和过氧化氢酶活性降低相关。此外，还观察到 PFC 星形胶质细胞和神经元细胞器的损失。相反，给予糖尿病大鼠 TDF-AgNPs 可以改善认知缺陷；并增加了谷胱甘肽、SOD 和过氧化氢酶，但降低了 PFC 丙二醛和 IL-1β 浓度。值得注意的是，TDF-AgNPs 可以防止 PFC 神经元和星形胶质细胞的损失以及神经元细胞器的形态畸变。 这项研究表明，TDF-AgNPs 通过银纳米颗粒的抗氧化和抗炎特性减轻认知缺陷，防止 PFC 星形胶质细胞和神经元的损失。 TDF-AgNPs可用于改善因长期施用TDF而引起的神经功能障碍。