L-arginine-induced chronic pancreatitis in mice: Evaluating effects of pirfenidone and simvastatin.

BACKGROUND: Chronic pancreatitis is a progressive, debilitating condition with no standardized treatment. Pirfenidone and simvastatin are potential therapeutic agents that exert anti-inflammatory and antifibrotic effects on pancreatic acinar cells. AIM: To evaluate the synergistic effects of pirfenidone and simvastatin in an L-arginine-induced chronic pancreatitis model in mice. METHODS: A preclinical, 7-week study was performed using a mouse model of L-arginine-induced chronic pancreatitis. The mice were divided into five groups: Normal control; model control; pirfenidone-treated; simvastatin-treated; and combination-treated (pirfenidone + simvastatin). Treatment started in week 3 after disease induction. Mice were euthanized at weeks 4 and 7 for blood collection and tissue sampling for histological and biomarker analysis, including cytokines, oxidative stress markers, and indicators of fibrosis. RESULTS: Combination therapy significantly reduced levels of tumor necrosis factor-alpha (11.10 ± 1.57 pg/mL vs 24.30 ± 2.00 pg/mL), interleukin-10 (11.70 ± 1.12 pg/mL vs 19.60 ± 1.27 pg/mL), and transforming growth factor-beta 1 (236.13 ± 6.95 pg/mL vs 550.52 ± 42.18 pg/mL) at week 7 (P < 0.05 vs model control). The glutathione peroxidase 1 level increased across all treatment groups, significantly in the pirfenidone-treated group (5.47 ± 0.34 IU/mL vs 5.04 ± 0.43 IU/mL; P < 0.05). Lipid peroxidation levels decreased significantly in the combination-treated group (111.87 ± 7.36 mmol/mL vs 192.85 ± 0.98 mmol/mL; P < 0.05). Histology revealed extensive collagen accumulation and damage to the exocrine pancreas in the model control group (vs treatment groups). Combination therapy elicited the least damage. CONCLUSION: Combination of pirfenidone and simvastatin demonstrated a synergistic therapeutic effect in reducing inflammation, fibrosis, and oxidative stress in an L-arginine-induced chronic pancreatitis mouse model, suggesting promise for chronic pancreatitis management.