Muscular Injection of Botox Exacerbates Seizures Through TNF-alpha and Oxidative Stress in Mice

Abstract

Background: Recent research has revealed the central adverse effects of Botox after intramuscular injection. The aim of this study was to examine the role of brain oxidative stress factors and circulatory cytokines as indicators of the severity of seizures following acute intramuscular (IM) injection of Botox in mice. Methods: Botox (1, 5 and 30 U, IM) was injected 60 minutes before inducing maximal electroshock (MES) seizures. Nitric oxide (NO), malondialdehyde (MDA) and glutathione (GSH) levels were measured in the brain. Tumor necrosis factor-alpha (TNF-α) levels were also determined in the serum. The motor coordination was assessed after Botox administration by using the chimney test. Results: Botox (5 and 10 U/kg, IM) significantly reduced the duration of hindlimb extension (HLE) and elevated levels of NO and MDA in the brain compared to the seizure group. Additionally, the administration of Botox (1 and 5 U, IM) increased the level of GSH in the brain, while 30 U decreased it. All Botox dosages demonstrated an enhancing effect on serum TNF-α levels compared to the seizure group. Botox at 5 and 30 U induced locomotor incoordination in mice. Conclusion: Our results showed that IM injection of Botox can lead to the exacerbation of tonic-clonic seizures by stimulating oxidative stress in the brain and increasing circulating TNF-α levels in mice.