High-density lipoproteins reduce the intestinal damage associated with ischemia/reperfusion and colitis.
High-density lipoproteins (HDLs) have been shown to reduce the organ injury and mortality in animal models of shock by reducing the expression of adhesion molecules and proinflammatory enzymes. However, there is limited evidence that HDL treatment reduces inflammation. As inflammation plays an important role in the development of colitis as well as ischemia/reperfusion (I/R) injury of the intestine, we have investigated the effects of HDL in animal models of associated with gut injury and inflammation (splanchnic artery occlusion [SAO] shock and dinitrobenzene sulfonic acid [DNBS]-induced colitis). We report here for the first time that the administration of reconstituted HDLs (recHDLs; 80 mg/kg i.v. bolus 30 min prior to ischemia in the SAO-shock model or 40 mg/kg i.v. every 24 h in the colitis model) exerts potent anti-inflammatory effects (e.g., reduced inflammatory cell infiltration and histological injury, and delayed the development of the clinical signs) in vivo. Furthermore, recHDL reduced the staining for nitrotyrosine and poly(ADP-ribose) (immunohistochemistry) and the expression of intercellular adhesion molecule-1 in the ileum of SAO-shocked rats and in the colon from DNBS-treated rats. Thus, recHDL reduces the inflammation caused by intestinal I/R and colitis. HDLs may represent a novel therapeutic approach for the therapy of inflammation of the gut.
Cuzzocrea
Salvatore
S
Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, 98100 Messina, Italy. salvator@unime.it
Dugo
Laura
L
Patel
Nimesh S A
NS
Di Paola
Rosanna
R
Cockerill
Gillian W
GW
Genovese
Tiziana
T
Thiemermann
Christoph
C
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000150:complications* / Q000473:pathology*; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000494:pharmacology; D007150:Immunohistochemistry; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007422:Intestines / Q000187:drug effects* / Q000473:pathology*; D008075:Lipoproteins, HDL / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis
D008075:Lipoproteins, HDL; D018799:Intercellular Adhesion Molecule-1; C045305:2,4-dinitrofluorobenzene sulfonic acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D004139:Dinitrofluorobenzene