Propylene Glycol Alginate Sodium Sulfate Alleviates  Cerulein‐Induced Acute Pancreatitis by Modulating  the MEK/ERK Pathway in Mice

Abstract

Previous studies have focused on the effects of propylene glycol alginate sodium sulfate (PSS) against thrombosis, but the anti‐inflammatory potential is unknown. Therefore, we specifically focused on the protective effects of PSS on cerulein‐induced acute pancreatitis (AP) using a mouse model, and investigated the mechanism of PSS on autophagy and apoptosis via the Mitogen‐activated protein kinase (MEK)/extracellular signal‐regulated kinase (ERK) pathway. Cerulein (100 ug/kg) was used to induce AP by ten intraperitoneal injections at hourly intervals in Balb/C mice. Pretreatment with vehicle or PSS was carried out 1 h before the first cerulein injection and two doses (25 mg/kg and 50 mg/kg) of PSS were injected intraperitoneally. The severity of AP was assessed by pathological score, biochemistry, pro‐inflammatory cytokine levels, myeloperoxidase (MPO) activity and MEK/ERK activity. Furthermore, pancreatic histological scores, serum amylase and lipase activities, tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β interleukin (IL)‐6 levels, and MPO activity were significantly reduced by PSS via up‐regulated MEK/ERK activity. The representative molecules of apoptosis and autophagy, such as Bcl‐2, Bax, Lc‐3, Beclin‐1, P62, were remarkably reduced. Taken together, these results indicate that PSS attenuates pancreas injury by inhibiting autophagy and apoptosis through a mechanism involving the MEK/ERK signaling pathway.

Keywords

• acute pancreatitis
•  apoptosis
•  autophagy
•  MEK/ERK pathway
•  PSS