Induction of heme oxygenase-1 improves impaired intestinal transit after burn injury.

Abstract

Burn injury has been shown to impair intestinal transit. The induction of heme oxygenase (HO)-1, the rate-limiting enzyme in heme degradation, has been demonstrated to provide protection against various injuries. The aim of this study was to investigate whether the induction of HO-1 by hemin would improve impaired intestinal transit after burn injury. Burn/sham rats were divided into 3 groups: saline solution, hemin (HO-1 inducer), and hemin plus tin protoporphyrin IX. Intestinal transit was measured with the use of phenol red and assessed with the geometric center. The gene and/or protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-1beta, HO-1, and p38 mitogen-activated protein kinase (p38 MAPK) was measured by real-time polymerase chain reaction and/or by Western blot analysis. Intestinal transit was delayed with burn injury and improved significantly with the induction of HO-1; burn injury significantly activated p38 MAPK and myeloperoxidase and increased gene and/or protein expression of iNOS, COX-2, IL-1beta, and HO-1. The administration of hemin led to a significant decrease in the activation of p38 MAPK and myeloperoxidase and the gene and/or protein expression of iNOS, COX-2, and IL-1beta. The induction of HO-1 improves burn-induced delayed intestinal transit. The beneficial effect of hemin treatment could be linked, at least in part, to the down-regulation of iNOS, COX-2, and IL-1beta expression, which suggests that the induction of HO-1 may provide an effective therapeutic measure for gut dysmotility after burn injury.