Therapeutic effects of resveratrol and β-carotene on L-arginine-induced acute pancreatitis through oxidative stress and inflammatory pathways in rats

Abstract

Acute pancreatitis (AP) is a severe inflammatory condition affecting the pancreas, often leading to systemic inflammation and organ dysfunction. This study evaluated the effects of resveratrol (RES) and β-carotene (βC) on L-arginine-induced AP in rats. Forty-eight male Sprague Dawley rats were divided into six groups: Control (C), RES (20 mg/kg), βC (50 mg/kg), AP, AP + RES, and AP + βC. The AP model was induced with 250 mg/100 g L-arginine intraperitoneally twice daily with a 1-h interval. The AP group showed significantly elevated oxidative stress (MDA) and reduced GSH levels (p < 0.001). Immunohistochemical (IHC) staining with anti-insulin antibody revealed reduced β + langerhans islet size in the AP group. qPCR analysis indicated significant upregulation of inflammatory genes NF-κB, TNF-α, and IL-1β (p < 0.001), and apoptotic genes Bax and Caspase-3, with downregulation of Bcl-2 (p < 0.001). RES and βC treatments significantly reduced MDA levels and increased GSH levels (p < 0.01 for both) compared to the AP group. The AP + RES and AP + βC groups exhibited preserved β + Langerhans islet size (p < 0.01), suppressed NF-κB, TNF-α, and IL-1β expression, reduced Bax and Caspase-3 levels, and increased Bcl-2 levels (p < 0.01). Histopathological findings supported these results. RES and βC confer significant effects against L-arginine-induced acute pancreatitis by reducing oxidative stress, preserving pancreatic islet integrity, suppressing inflammatory responses, and modulating apoptotic pathways. RES demonstrated a slightly superior efficacy in reducing inflammation and oxidative stress markers, suggesting it may be more effective in treating acute pancreatitis.

Keywords: Acute pancreatitis; Apoptosis; L-arginine; Oxidative stress; Resveratrol; İnflammation; β‐carotene.

Fig. 1

Histopathological examination of the pancreas in different groups: (A) Control group, (B) RES group, (C) βC group. Normal histological appearance. (D) AP group. Severe degenerative-necrotic changes in the cells of Langerhans islets (arrow) and acinar cells (arrowhead). (E) AP + RES group. Severe degenerative-necrotic changes in the cells of Langerhans islets (arrow) and moderate changes in acinar cells (arrowhead). (F) AP + βC group. Mild degenerative-necrotic changes in the cells of Langerhans islets (arrow) and acinar cells (arrowhead) (H&E staining, magnification ×40).

Fig. 2

Levels of oxidative stress markers MDA and GSH in pancreatic tissues. Values are expressed as mean ± SD. Statistical significance: Control vs. others: *** p < 0.001; AP vs. others: ### p < 0.001.

Fig. 3

Diameter and area of β + Langerhans islets (arrowhead) in different groups (immunohistochemical staining with anti-insulin antibody). (A) Control group, (B) RES group, (C) βC group. Normal histological appearance of β + Langerhans islets. (D) AP group. Group with the smallest β + Langerhans islets. (E) AP + RES group. Group with larger β + Langerhans islets. (F) AP + βC group. Group with the largest β + Langerhans islets (Immunohistochemistry, magnification × 20).

Fig. 4

Relative mRNA transcript levels of inflammatory genes NF-κB, TNF-α, and IL-1β in pancreatic tissues. Statistical significance: Control vs. others: *** p < 0.001; AP vs. others: ^### p < 0.001.

Fig. 5

Relative mRNA transcript levels of apoptotic genes Bax and Caspase-3, and anti-apoptotic gene Bcl-2 in pancreatic tissues. Statistical significance: Control vs. others: *** p < 0.001; AP vs. others: ^### p < 0.001.