Why could ethyl pyruvate attenuate severe acute pancreatitis?

Excessive activation of inflammatory mediator cascade during SAP is a major cause of distant organ injury and the high mortality. Cytokines such as TNF- alpha and IL-1 beta are released early in the development of systemic inflammatory response. This leaves a narrow therapeutic window for administration of therapeutics and delayed delivery of that anti-inflammatory therapeutics is not effective after the inflammatory mediator cascade has developed.

A research article to be published on July 28, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Wang from Centre of Pancreatic Surgery of Xiehe Hospital, Tongji Medical College, Huazhong University of Sciecne and Technology, demonstrated that the serum levels of HMGB1 began to rise significantly at 12 h, and maintained at high levels up to 48 h after induction of experimental SAP in rats. The delayed kinetics indicated that HMGB1 may provide a broader therapeutic window for treating this lethal systemic inflammatory disease. EP was proved could inhibit HMGB1 release from macrophages and prevent the accumulation of serum HMGB1 levels in mice with lethal sepsis through inhibiting NF- kappaB and p38 MAPK signaling. The research, performed by this team, investigated whether delayed EP therapy attenuates experimental SAP via reducing serum HMGB1 levels in rats or not.

In this study, EP significantly reduced serum HMGB1 levels in rats with SAP, even though began delivering EP at 12 h after induction of SAP. It also significantly protected against liver, renal and lung injury, and prolonged survival time of rats. Ethyl pyruvate, a stable lipophilic pyruvate derivatives, is a nontoxic food additive. According to this article, EP may serve potentially as an effective and low-cost therapeutic option against the inflammatory response and MODS in SAP patients.

This report is of interest and considerable potential importance because it indicates that delayed treatment of rats with experimental severe acute pancreatitis with ethyl pyruvate is associated with a reduction of HMGB1 levels in blood; a decrease in lung, kidney, and liver injury; and prolonged survival. The "therapeutic window" for inhibiting this inflammatory mediator appears to be more favorable than for some other mediators which more rapidly reach a peak in the blood.

Reference: Yang ZY, Ling Y, Yin T, Tao J, Xiong JX, Wu HS, Wang CY. Delayed ethyl pyruvate therapy attenuates experimental severe acute pancreatitis via reducing serum HMGB1 levels in rats. World J Gastroenterol 2008; 14(28): 4529-4534 http://www.wjgnet.com/1007-9327/14/4529.asp

Correspondence to: Chun-You Wang, Department of Pancreatic Surgery, Xiehe Hospital, Tongji Medical College, Huazhong University of Sciecne and Technology, 1277 Jiefang Road, Wuhan 430022, Hubei Province, China. dryzy@163.com Telephone: +86-27-85351621 Fax: +86-27-85351673

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.

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