Papaverine Has Therapeutic Potential for Sepsis-Induced Neuropathy in Rats, Possibly via the Modulation of HMGB1-RAGE Axis and Its Antioxidant Prosperities

Aim Our aim was to investigate the possible neuroprotective properties of papaverine in sepsis-induced critical illness neuropathy (SCIN) through the evaluation of various inflammatory biochemical markers, including interleukin 6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha), and oxidative stress biomarkers, such as malondialdehyde (MDA) and lactic acid. Additionally, evaluation of the HMGB1/RAGE interactions in SCIN was another target of this research. Method To create a sepsis model, a procedure involving intraperitoneal injection of feces was performed on 48 rats. The rats were divided into four equal groups: sham operated, controls and those receiving 20 and 40 mg/kg/day papaverine. After five-day treatments, compound muscle action potential (CMAPs) with electroneuromyography (ENMG) was recorded in all rats. Following ENMG evaluations, the plasma levels of sRAGE, HMGB1, TNF-alpha, IL-6, CRP, MDA and lactic acid were measured. Results TNF-alpha, CRP, IL-6, HMGB1, MDA, and lactic acid levels were significantly elevated in the SCIN group, and sRAGE levels were significantly decreased. In recipients of papaverine (20 and 40 mg/kg) treatment, these biochemical findings were improved. Furthermore, electrophysiological findings also showed significant improvement in both 20 and 40 mg/kg papaverine treated groups. Conclusion Papaverine demonstrates neuroprotective effects in a rat model of SCIN. Considering its anti-inflammatory and antioxidant properties, papaverine's neuroprotective effects possibly stem from the suppression of the RAGE-HMGB1 axis.