Ibudilast and octreotide can ameliorate acute pancreatitis via down-regulation of the inflammatory cytokines and Nuclear Factor- Kappa B expression

Abstract

Background: Acute pancreatitis (AP) is severe inflammation of the pancreas that can be of two major types: mild AP and severe AP. In this case, some pancreatic cells can produce various pro-inflammatory cytokines and transcription factors thereby affecting the function of pancreas. Objective: to study the efficacy of Ibudilast in comparison with octreotide, in a rat model of AP. Methods: A total of 48 male rats were randomly divided into 8 groups (6 per each). AP was induced by L-arginine model which has a high reproducibility. Octreotide and Ibudilast were administered individually or in combination at 0, 8or 16 hr after induction. After 24 hr of treatment, each rat was weighed and blood samples were collected for measurement of biochemical markers, and then the pancreas was extracted to obtain the pancreatic weight to the total body weight (PW/TBW) ratio and for vertical gel electrophoresis experiments. Results: In both octreotide-treated group and ibudilast-treated group, there were statistically significant decrease in serum pro-calcitonin (PCT) and tumor necrosis factor-alpha (TNF-α) when compared to control group or sham group, as well as, a decrease in PW/TBW ratio and in nuclear factor kappa B (NFκB)protein level using vertical gel electrophoresis. However, in octreotide + ibudilast-treated group there was no statistically significant difference when compared with groups treated with either agents. Conclusion: Ibudilast and octreotide can significantly attenuate the local and systemic effect of AP. The efficacy of ibudilast and octreotide are almost the same. Co-treatment of rats with both Ibudilast and octreotide has no preferential effect when compared with rats treated with the individual agent.