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

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.