Vinpocetine ameliorates L-arginine induced acute pancreatitis via Sirt1/Nrf2/TNF pathway and inhibition of oxidative stress, inflammation, and apoptosis

Abstract

Objectives: Acute pancreatitis (AP) is a common severe critical illness with a high mortality rate. We aimed to study the effect of vinpocetine (Vinpo) in the treatment of AP because of its anti-inflammatory, antioxidant, and antiapoptotic effects.

Materials and methods: Thirty two adult male albino Wistar rats were randomized to four groups: control group, Vinpo group (20 mg/kg.P.O.), l-arginine group (two intraperitoneal injections of l-arginine 2.5 g/kg, 1 h apart), and Vinpo + L-arginine group. Vinpo administration was once daily for 7 consecutive days and started 1 h later after l-arginine administration. We measured serum enzyme biomarkers (lipase and amylase), levels of pancreatic malondialdehyde (MDA), total antioxidant capacity (TAC), reduced glutathione (GSH), total sulfhydryl (T-SH), total nitrite/nitrate (NOx), Interluken-6 (IL-6), tumor necrosis factor-alpha (TNF-α), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), Sirtuin type 1 (Sirt1), and caspase-3 activity. Furthermore; histological changes, anti-insulin, and inducible nitric oxide synthase (iNOS) immuno-expressions were examined.

Results: l-arginine group displayed AP as manifested by a significant increase in serum lipase and amylase, MDA, NOx, IL-6, TNF-α, caspase-3 with iNOS immuno-expression. Histological changes indicating marked pancreatic injury were observed together with a significant decrease in TAC, GSH, T-SH, Nrf2, Sirt1 levels, and anti-insulin immuno-expression. Vinpo showed a significant amelioration in all parameters.

Conclusion: Vinpo possesses potent ameliorative effects against AP by decreasing oxidative stress, inflammatory process, and apoptosis through regulation of the Sirt1/Nrf2/TNF-α pathway.

Keywords: Acute pancreatitis; Caspase-3; Sirtuin type 1; Tumor necrosis factor alpha; Vinpocetine; l-Arginine.