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阿昔洛韦的神经毒性作用:对雄性Wistar大鼠氧化应激、炎症和神经递质动力学的影响

Neurotoxic effects of acyclovir: impacts on oxidative stress, inflammation, and neurotransmitter dynamics in male Wistar rats.

作者信息

Obembe O O, Mustapha R A, George E T, Bayo-Olugbami A A, Tokunbo O S, Akhigbe R E

机构信息

Department of Physiology, Osun State University, Osogbo, Osun State, Nigeria.

Department of Anatomy, Osun State University, Osogbo, Osun State, Nigeria.

出版信息

Metab Brain Dis. 2025 Sep 2;40(7):255. doi: 10.1007/s11011-025-01694-8.

DOI:10.1007/s11011-025-01694-8
PMID:40892179
Abstract

BACKGROUND

Acyclovir is a potent antiviral agent with variable side effects on the central nervous system. Although previous studies have shown that acyclovir has neurotoxic effects, there is a dearth of scientific information on the mechanisms through which acyclovir induces neurotoxicity.

AIM

Thus, the present study assessed the impact of acyclovir on oxidative stress, inflammatory markers, and neurotransmitter levels in the cerebellum, prefrontal cortex, and basal ganglia and its potential impact on cognition and motor function.

MATERIALS AND METHODS

Twenty-eight male Wistar rats (120-150 g) were randomly assigned into four equal groups. The control group received distilled water while acyclovir-treated groups received single daily treatment at doses of 10, 20, and 40 mg/kg bw orally for 28 days.

RESULTS

Acyclovir, at 20 and 40 mg/kg but not at 10 mg/kg, induced a decline in memory, spatial learning, and motor coordination when compared with the control. Also, the brain levels of antioxidants (catalase, superoxide dismutase, and glutathione) and anti-inflammatory cytokine IL-10 were significantly reduced while malondialdehyde and pro-inflammatory cytokines (IL-6 and TNF-α) were increased in the cerebellum, prefrontal cortex, and basal ganglia in acyclovir-treated rats, particularly in those treated with 20 and 40 mg/kg. Serotonin levels increased while dopamine levels decreased in the brain tissues of acyclovir-treated rats. However, IL-1β was not significantly affected.

CONCLUSION

Acyclovir impaired motor function, muscle strength, and memory by inducing derangement of the brain's oxidative markers, cytokines, and neurotransmitter levels.

摘要

背景

阿昔洛韦是一种强效抗病毒药物,对中枢神经系统有多种副作用。尽管先前的研究表明阿昔洛韦具有神经毒性作用,但关于阿昔洛韦诱导神经毒性的机制,科学信息匮乏。

目的

因此,本研究评估了阿昔洛韦对小脑、前额叶皮质和基底神经节中氧化应激、炎症标志物和神经递质水平的影响及其对认知和运动功能的潜在影响。

材料与方法

将28只雄性Wistar大鼠(120 - 150克)随机分为四组,每组数量相等。对照组给予蒸馏水,阿昔洛韦治疗组每日口服剂量分别为10、20和40毫克/千克体重,持续28天。

结果

与对照组相比,20毫克/千克和40毫克/千克剂量的阿昔洛韦会导致记忆、空间学习和运动协调性下降,但10毫克/千克剂量未出现此现象。此外,阿昔洛韦治疗的大鼠小脑、前额叶皮质和基底神经节中的抗氧化剂(过氧化氢酶、超氧化物歧化酶和谷胱甘肽)和抗炎细胞因子IL - 10水平显著降低,而丙二醛和促炎细胞因子(IL - 6和TNF - α)水平升高,尤其是在接受20毫克/千克和40毫克/千克剂量治疗的大鼠中。阿昔洛韦治疗的大鼠脑组织中血清素水平升高,多巴胺水平降低。然而,IL - 1β未受到显著影响。

结论

阿昔洛韦通过诱导大脑氧化标志物、细胞因子和神经递质水平紊乱,损害运动功能、肌肉力量和记忆。

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