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

ObjectiveWe aim to study the protective effect of menadione on caerulein-induced acute pancreatitis (AP) and associated lung injury and to explore the possible mechanism. MethodsMale 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. ResultsAdministration 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. ConclusionThe 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.