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

Abstract

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.

A pilot study on intravenous N-Acetylcysteine treatment in patients with mild-to-moderate COVID19-associated acute respiratory distress syndrome

“…In fact, NAC not only does not increase the risk of infections but also, through regulatory actions on the immune system, may decrease the risk of infections [33]. Furthermore, it is well-known that NAC against acute cardiovascular and neurological events, such as myocardial infarction and stroke, has protective effects [47,48]; this effect may also be helpful for some patients at an increased risk of cardiovascular and neurological complications associated with COVID-19 [49,50]. Moreover, one of the main properties of NAC that makes it a proper candidate in preventing and treating COVID-19 is its excellent safety and tolerability even when used in high doses.…”

N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)

“…Acrolein-mediated damage after stroke has been implicated in the size of strokes in animal studies and NAC has been shown to reduce the size of the infarct [ 117 ]. In a recent randomized double-blind placebo-controlled trial using NAC 4 grams four times a day for 72 hours at the onset (within 24 hours) of an ischemic stroke, the follow-up National Institute of Health Stroke Scale at 90 days resulted in a better outcome profile in both neurological deficit and disability [ 118 ].…”

Emerging Role of Ferroptosis in the Pathogenesis of Ischemic Stroke: A New Therapeutic Target?

“…However, after ischemic stroke the level of endogenous antioxidants decreases, leading to oxidative stress. When patients with acute ischemic stroke were treated with a neuroprotective drug N-acetylcysteine, serum levels of SOD and glutathione peroxidase significantly increased, whereas the National Institute of Health Stroke Scale scores decreased ( Sabetghadam et al, 2020 ). Other drugs were also shown to regulate antioxidant levels and exert neuroprotective effects in animal models of cerebral ischemia.…”