astaxanthine and Pancreatitis

Astaxanthin (ATX) is a naturally occurring carotenoid and a potent antioxidant. Various anti-inflammatory effects of ATX have been examined. We aimed to investigate the protective effect of ATX and its mechanism in a cerulein-induced acute pancreatitis rat model.. The rats were randomized into 2 main groups as control (C) and acute pancreatitis group (AP). AP group was subsequently divided into subgroups as AP+vehicle (AP), AP+ATX, and ATX+peroxisome proliferator-activated receptor-alpha antagonist GW6471 (ATX+GW) groups. To induce AP, the rats were administered cerulein (50 µg/kg, intraperitonally [ip]) at 1 hour intervals, whereas the C group received saline. The AP group was treated with vehicle olive oil, ATX 40 mg/kg/orally, or GW6471 and ATX (GW1 mg/kg/ip; ATX; 40 mg/kg/peroral). Treatments were administered after the 1st cerulein injection. At the 7th hour after the final injection, the rats were killed and the pancreatic tissue was used for the determination of malondialdehyde (MDA), glutathione (GSH), and myeloperoxidase (MPO) activities and luminol-lucigenin chemiluminescence levels. Serum amylase, lipase, and histopathological analyses were performed.. Elevated serum lipase and amylase levels in the vehicle-treated AP group (p<0.01) decreased in the ATX and ATX+GW groups (p<0.05). In the AP groups, GSH was reduced and MDA, MPO, luminol, and lucigenin levels were increased (p<0.05-0.001). ATX reversed these changes (p<0.05-0.001). The vehicle-treated group revealed significant severe cytoplasmic degeneration and vacuolization, whereas ATX ameliorated these destructions. GW6471 did not abolish the positive effects of ATX biochemically or histologically.. ATX has a potent protective effect on AP via its radical scavenging and antioxidant properties. Therefore, we believe that ATX may have therapeutic potential.

Topics: Acute Disease; Animals; Antioxidants; Ceruletide; Disease Models, Animal; Oxidative Stress; Pancreas; Pancreatitis; Rats; Xanthophylls

A various of pharmacological effects of astaxanthin has been confirmed. However, the mechanism underlying protective effect of astaxanthin on acute pancreatitis (AP) induced by cerulein still unclear. The present study is to investigate the mechanism underlying the effect of astaxanthin on autophagy and apoptosis via the JAK/STAT3 pathway.. Intraperitoneal injection of cerulein at hourly intervals followed by lipopolysaccharide injection were used in Balb/C mice. Vehicle or astaxanthin, which intraperitoneal injected in two doses (20 mg/kg and 40 mg/kg), were injected in mice 1 h before the first cerulein injection. At 3 h after the last injection, when the pathological changes were most severe, pancreatic tissue was analyzed by pathologically scored and hematoxylin and eosin (H&E) staining. The severity of AP was assessed by histological grading, proinflammatory cytokine levels, biochemistry, myeloperoxidase (MPO) activity, and analysis of JAK/STAT3 activity.. Astaxanthin administration markedly reduced serum digestive enzyme activities, pancreatic histological scores, proinflammatory cytokine levels (tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), and Interleukin-6 (IL-6)), MPO and JAK/STAT3 activity.. Collectively, these results indicate that astaxanthin inhibits pancreatic injury in AP by targeting JAK/STAT3-mediated apoptosis and autophagy.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Apoptosis; Autophagy; Ceruletide; Cytokines; Disease Models, Animal; Humans; Inflammation Mediators; Janus Kinases; Lipopolysaccharides; Male; Mice; Mice, Inbred BALB C; Pancreas; Pancreatitis; Peroxidase; STAT3 Transcription Factor; Xanthophylls