Evidence for a Beneficial Effect of Oral N-acetylcysteine on Functional Outcomes and Inflammatory Biomarkers in Patients with Acute Ischemic Stroke

Purpose: Numerous preclinical studies have demonstrated the potential neuroprotective effects of N-acetylcysteine (NAC) in the treatment of brain ischemia. Accordingly, the present study aimed to assess the potential therapeutic effects of oral NAC in patients with acute ischemic stroke.

Patients and methods: In a randomized, double-blind, placebo-controlled trial study, 68 patients with acute ischemic stroke with the onset of symptoms less than 24 hours were randomly assigned to either the NAC-treated group or placebo-treated group. NAC and matched placebo were administrated by a 72-hour oral protocol (initially 4 grams loading dose and after on, 4 g in 4 equal divided doses for more 2 days). The primary outcomes were quantification of any neurologic deficit by the use of the National Institute of Health Stroke Scale (NIHSS) score and functional disability by the use of the modified Rankin scale (mRS) at 90 days after stroke. Additionally, serum levels of markers of oxidative stress and inflammation as a main mechanism of its action were assessed at baseline and the end of 3-day treatment protocol.

Results: NAC-treated patients in comparison with placebo-treated patients showed a significantly lower mean NIHSS scores at day 90 after stroke. A favorable functional outcome which was defined as an mRS score of 0 or 1, also in favor of NAC compared to placebo was noted on day 90 after stroke (57.6% in the NAC-treated group compared with 28.6% in the placebo-treated group). Further, compared to the placebo, NAC treatment significantly decreased serum levels of proinflammatory biomarkers such as interleukin 6 (IL-6), soluble intercellular cell adhesion molecule-1 (sICAM-1), nitric oxide (NO), malondialdehyde (MDA), and neuron-specific enolase (NSE) and significantly increased serum levels of anti-oxidant biomarkers such as superoxide dismutase (SOD), glutathione peroxidase (GPx), and total thiol groups (TTG).

Conclusion: The pattern of results suggests that oral NAC administration early after an acute ischemic stroke is associated with a better outcome profile in terms of acute neurological deficit and disability grade compared to placebo. NAC may improve neurological outcomes of patients with stroke at least in part by its antioxidant and anti-inflammatory effects.

Keywords: N-acetylcysteine; antioxidant and anti-inflammatory compounds; inflammation; ischemic stroke; oxidative stress.