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Digestive Diseases and Sciences

, Volume 51, Issue 2, pp 318–325 | Cite as

Morphine-Induced Degradation of the Host Defense Barrier

Role of Intestinal Mucosal Injury
  • Lia Frenklakh
  • Rajani S. Bhat
  • Madhu Bhaskaran
  • Shilpa Sharma
  • Meera Sharma
  • Amit Dinda
  • Pravin C. SinghalEmail author
Surgery

Abstract

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.

Key Words

opiates intestinal ulcers macrophages apoptosis nitric oxide 

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Copyright information

© Springer Science + Business Media, Inc. 2006

Authors and Affiliations

  • Lia Frenklakh
    • 1
  • Rajani S. Bhat
    • 1
  • Madhu Bhaskaran
    • 1
  • Shilpa Sharma
    • 2
  • Meera Sharma
    • 2
  • Amit Dinda
    • 1
  • Pravin C. Singhal
    • 1
    • 3
    Email author
  1. 1.Department of MedicineNorth Shore University Hospital and Long Island Jewish Medical CenterNew Hyde ParkUSA
  2. 2.Department of MicrobiologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  3. 3.Division of Kidney Diseases and HypertensionLong Island Jewish Medical CenterNew Hyde Park

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