THE POTENTIAL THERAPEUTIC EFFECT OF APRIMELAST (OTEZLA) ON L-ARGININE INDUCED ACUTE PANCREATITIS IN RATS

Abstract

Background: Acute pancreatic inflammation is an emergency worldwide. Aprimelast (Otezla) is an orally active drug inhibiting phosphodiesterase-4 (PDE4) &modulate the inflammatory mediators. NO research was done to detect its role in treatment of acute pancreatitis (AP). Aim: this research was designed to determine the role of Aprimelast on AP produced by L-arginine. Materials & methods: A rat model of AP was developed by two injections of L-arginine 250 mg/kg body weight, intraperitoneal (IP), separated by a one-hour period. The treatment group received Aprimelast at a single daily oral dosage of 20mg/kg body weight for five consecutive days after IP injections of L-arginine at the same dose as before.AT the last of treating period, blood samples were taken for the assessment of the parameters of oxidative stress glutathione [GSH], malondialdehyde [MDA], then rats were sacrificed. The pancreas of all treated animals was excised, prepared for estimation of tumor necrotic factor (TNFalpha) & interleukin-10 (IL-10) in tissues and histopathological examination. Results: Rats with AP had histological alterations consistent with pancreatic tissue impairment, and elevated blood glucose, serum amylase, and lipase enzyme activities. Additionally, AP rats had increased levels of the pancreatic inflammatory biomarker TNFalpha and decreased levels of the anti-inflammatory biomarker IL-10. Additionally, the oxidative stress biomarker MDA was elevated in AP, whereas the antioxidant GSH level was reduced as contrasted to control group. Co-administration of Aprimelast led to substantial improvements in both pre-existing parameters and histology. Conclusion: These results suggested that Aprimelast may have beneficial therapeutic effect on Larginine induced AP in adult albino rats owing to its anti-inflammatory and anti-oxidative stress effects.