INVESTIGATING THE ROLE OF INFLAMMATORY, OXIDATIVE AND NITROSATIVE STRESS PATHWAYS IN ALCOHOL USE DISORDER PATIENTS WITH PERIPHERAL NEUROPATHY

Peripheral neuropathy is the most common neurological complication of alcohol use disorder (AUD), yet its underlying mechanisms remain poorly understood. This study aimed to investigate the role of inflammatory, oxidative, and nitrosative stress (IO&NS) pathways in the pathobiology of peripheral neuropathy in AUD.

In this cross-sectional study, AUD patients with neuropathy (AUD-NP; n = 57), AUD patients without neuropathy (AUD-NNP; n = 35), and healthy controls (HC; n = 25) were recruited. Neuropathy was diagnosed using nerve conduction studies. Oxidative and nitrosative stress were assessed by measuring malondialdehyde (MDA), catalase (CAT) activity, superoxide dismutase (SOD) activity, glutathione peroxidase (GPX) activity, total antioxidant capacity, and total nitrate metabolites (TNM) in serum. Plasma levels of IL-1β, IL-6, IL-17A, IL-23, TNF-α, and IFN-γ were quantified. Gene expression analysis of Il1b, Il6, Il17a, Il23, Tnfa, Ifng, Sod1, Sod2, Gpx, and Cat was performed using peripheral blood mononuclear cells. The AUD-NP group showed significantly higher plasma IL-6 [H(2)=12.524, p=0.002] and serum TNM [H(2)=6.05, p=0.048] levels, along with reduced CAT activity [H(2)= 7.45, p=0.024], compared to the AUD-NNP and HC groups. Gene expression of Il1b [H(2)=9.41, p=0.009], Il23 [H(2)=19.62, p=<0.001], Ifng [H(2)=8.94, p=0.011] and Tnfa [H(2)=8.48, p=0.014] was significantly upregulated in AUD-NP patients, whereas Sod1 [H(2)=13.701, p=0.001] and Cat [H(2)=21.976, p <0.001] expression was significantly downregulated. These findings suggest enhanced pro-inflammatory activity, impaired antioxidant defence and nitrosative stress in AUD patients with peripheral neuropathy. Components of the IO&NS pathway may serve as potential biomarkers for identifying AUD patients at increased risk of developing peripheral neuropathy.