Morphine-induced degradation of the host defense barrier role of intestinal mucosal injury.
The effect of morphine on intestinal ulcer formation and on the degradation of the host defense barrier was studied. Mice receiving morphine (MRM) showed mucosal ulcer formation in the ileum and in the upper third of the colon. In in vitro studies, morphine enhanced apoptosis of cultured human colonic cells (HCC). Nitric oxide synthase (NOS) inhibitors attenuated the proapoptotic effect of morphine. Moreover, morphine stimulated NO generation by HCCs. MRM also showed a breach in the host defense barrier as well as injury to peritoneal macrophages. Although NOS inhibitors completely prevented morphine-induced intestinal ulcer formation, it provided only partial protection against a breach in the host defense barrier and peritoneal macrophage injury. Propranolol did not inhibit the induction of intestinal ulcer formation in MRM; nevertheless, propranolol prevented a breach in the host defense barrier as well as macrophage injury in MRM, whereas hemin exacerbated macrophage injury as well as the breach in the host defense barrier of MRM. These findings suggest that morphine-induced intestinal injury is mediated through NO generation. However, the degradation of the host defense barrier correlates with macrophage injury, but not intestinal injury.
Department of Medicine, North Shore University Hospital and Long Island Jewish Medical Center, New Hyde Park, New York 11042, USA.
Lia
L
Frenklakh
Rajani S
RS
Bhat
Madhu
M
Bhaskaran
Shilpa
S
Sharma
Meera
M
Sharma
Amit
A
Dinda
Pravin C
PC
Singhal
D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
D009294:Narcotics; D009569:Nitric Oxide; D009020:Morphine; D019001:Nitric Oxide Synthase