Hui Zhang1, Wenjuan Yang2, Yueyue Li3, Liangkai Hu4, Ying Dai5, Jianqing Chen6, Shuqi Xu7, Xuanfu Xu8, Haiqiong Jiang9. 1. Department of Gastroenterology, the Shidong Hospital of Shanghai, Anhui Medical University, Shanghai, China. Electronic address: viannezhzxz@163.com. 2. Department of Emergency, the Tenth People's Hospital of Shanghai, Tongji University, Shanghai, China. Electronic address: yangwj20130425@163.com. 3. Department of Gastroenterology, the Shidong Hospital of Shanghai, Anhui Medical University, Shanghai, China. Electronic address: yueyueliYYL@163.com. 4. Department of Gastroenterology, the Shidong Hospital of Shanghai, Anhui Medical University, Shanghai, China. Electronic address: huliangkai800116@163.com. 5. Department of Gastroenterology, the Shidong Hospital of Shanghai, Anhui Medical University, Shanghai, China. Electronic address: dynchengmo@163.com. 6. Department of Gastroenterology, the Shidong Hospital of Shanghai, Anhui Medical University, Shanghai, China. Electronic address: cjqing1202@163.com. 7. Department of Gastroenterology, the Shidong Hospital of Shanghai, Anhui Medical University, Shanghai, China. Electronic address: sandy19840618@hotmail.com. 8. Department of Gastroenterology, the Shidong Hospital of Shanghai, Anhui Medical University, Shanghai, China. Electronic address: shuanfusky@aliyun.com. 9. Department of International Medical Care Center, Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai 200080, China. Electronic address: jianghaiqiong@medmail.com.cn.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Collectively, these results indicate that astaxanthin inhibits pancreatic injury in AP by targeting JAK/STAT3-mediated apoptosis and autophagy.
BACKGROUND: 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. METHODS: 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. RESULTS: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. CONCLUSION: Collectively, these results indicate that astaxanthin inhibits pancreatic injury in AP by targeting JAK/STAT3-mediated apoptosis and autophagy.
Authors: Mariam A Fouad; Mohamed M Sayed-Ahmed; Etimad A Huwait; Hafez F Hafez; Abdel-Moneim M Osman Journal: BMC Pharmacol Toxicol Date: 2021-01-28 Impact factor: 2.483