Menadione (vitamin K3) inhibits hydrogen sulfide and substance P via NF-кB pathway in caerulein-induced acute pancreatitis and associated lung injury in mice

Abstract

Objective: We aim to study the protective effect of menadione on caerulein-induced acute pancreatitis (AP) and associated lung injury and to explore the possible mechanism.

Methods: Male Swiss mice randomized into control and different experimental groups. AP was induced in mice by six hourly intraperitoneal (i.p) injections of caerulein (50 μg/kg at 1 h interval). Menadione (10 mg/kg) was administered one hour (i.p, 10 mg/kg) after the first caerulein injection and control animals were given hourly intraperitoneal (i.p) injection of isotonic sodium chloride solution for 6 hours.

Results: Administration of menadione attenuated the severity of AP and associated lung injury as shown by the histopathology, reduced MPO and serum amylase activity. Further, the anti-inflammatory effect of menadione was associated with a reduction of pancreatic and pulmonary proinflammatory cytokine interleukin 1β (IL-1β) and hydrogen sulfide (H₂S). Moreover, menadione inhibited caerulein-induced cystathionine-γ-lyase, preprotachykinin-A (PPTA) and neurokinin-1 receptor (NK-1R) expression in pancreas and lungs. Also menadione further enhances the beneficial effect by reducing caerulein-induced nuclear factor (NF) -κB activation in both pancreas and lung.

Conclusion: The present findings show for the first time that in AP, menadione may exhibit an anti-inflammatory effect by down-regulating substance-P and H₂S signaling via the NF-кB pathway.

Keywords: Acute pancreatitis; Hydrogen sulphide; Menadione; Neurokinin-1 receptor; Preprotachykinin-A.