Shock‐related intestinal necrosis may be caused by free fatty acid formation and release

• Published in: The FASEB journal 2007, Vol.21 (6), p.A847-A847
• Main Authors: Penn, Alexander H, Schmid‐Schönbein, Geert W
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.21.6.A847

We have recently shown that entry of pancreatic digestive enzymes into an ischemic intestine leads to formation of cytotoxic mediators and shock. Homogenates of intestinal wall digested by pancreatic proteases are also cytotoxic (by flow cytometric measurements of propidium iodide uptake in leukocytes). After lipid/aqueous separation, the lipid fraction is cytotoxic even if the unfractionated homogenate is not cytotoxic. The proteinaceous fractions are protective against cytotoxicity unless digested by proteases. We hypothesize that lipases in intestinal homogenates create free fatty acids (FFAs) from triglycerides, but that these FFAs are bound to lipid binding proteins such as albumin unless those proteins are digested by pancreatic proteases. Fluorescent substrate shows that lipase activity is significantly elevated in intestinal wall homogenates. Addition of bovine serum albumin prevents cytotoxicity unless it is prior digested by pancreatic proteases. FFA levels are elevated in intestinal homogenates above cytotoxic values, and rat serum albumin levels are significantly decreased in the cytotoxic digested homogenates versus the non‐cytotoxic undigested homogenates (by immunoturbidometric method). This evidence suggests that in ischemic intestines FFAs may be cytotoxic, created by lipases and released from lipid binding proteins by protease digestion. Supported in part by HL 67825.