Elucidating the role of oxidative stress in the therapeutic effect of rutin on experimental acute pancreatitis

Abstract

Introduction: Acute pancreatitis (AP) may be severe and cause hospitalization or death, and the available treatment is insufficient to control pancreatic inflammation and pain. Rutin is a natural flavonoid with the potential to treat AP via anti-inflammatory, antinociceptive, and antioxidant activities.

Aim: This study investigated the beneficial effects of rutin on experimental AP induced by l-arginine administration in mice.

Methods: The l-arginine-induced AP model was used in Swiss mice (n = 6–8). Mice submitted to AP induction were treated with rutin (37.5, 75, or 150 mg kg⁻¹, p.o.) or vehicle (saline) after 24, 36, 48, and 60 h of AP induction. Abdominal hyperalgesia, serum enzymes, interleukin (IL)-6 levels, pancreatic inflammatory parameters, malondialdehyde (MDA) levels, antioxidant enzyme activities, and 3-nitrotyrosine contents were measured 72 h after induction.

Results: Mice submitted to l-arginine injections developed abdominal hyperalgesia and increased serum amylase, lipase, C-reactive protein and IL-6 concentrations; and increased pancreatic myeloperoxidase activity, edema index, MDA, and 3-nitrotyrosine contents. A marked decrease in catalase activity was observed in the pancreas without alterations of superoxide dismutase (SOD) activity compared with the control group. Rutin treatment significantly impaired all the parameters that were altered by AP induction, but increased catalase and SOD activities in the pancreas compared with the vehicle-treated group.

Conclusion: Rutin treatment exerted a protective effect on l-arginine-induced AP by mechanisms involving the reduction of oxidative stress, which suggests that this flavonoid has a potential for future approaches designed for the management of AP.

Keywords:

• Pancreatic injury
• antioxidant
• flavonoid
• inflammation
• pain

Acknowledgements

The authors thank Ms. Marcela Santos Santana for technical help.

Disclosure statement

The authors report that they have no conflicts of interests. The authors thank "Coordenação de Aperfeiçoamento de Pessoal de Nível Superior" (CAPES; Social Demand Program of Scholarships) and Conselho Nacional de Pesquisa e Desenvolvimento Científico (CNPq) for financial support. E. A. C., M. N. M., and S. K. P. C. are beneficiaries of CNPq productivity grants.