Systemic Administration of Sialorphin Attenuates Experimental Colitis in Mice via Interaction With Mu and Kappa Opioid Receptors.
OBJECTIVE
Pharmacological treatment and/or maintenance of remission in inflammatory bowel disease [IBD] is currently one of the biggest challenges in the field of gastroenterology. Here we aimed to assess the anti-inflammatory effect and the mechanism of action of sialorphin, the natural blocker of the endogenous opioid peptide-degrading enzymes neprilysin [NEP] and aminopeptidase N [APN], in mouse models of IBD and the changes in the expression of these enzymes in IBD patients.


METHODS
We used two models of experimental colitis in mice [2,4,6-trinitrobenzene sulphonic acid [TNBS]- and dextran sulphate sodium [DSS]-induced]. Macroscopic score, ulcer score, colonic wall thickness, and myeloperoxidase [MPO] activity were recorded. Additionally, we measured the expression of NEP and APN in the colon of IBD patients and healthy controls.


RESULTS
We showed that sialorphin attenuated acute, semichronic, and relapsing TNBS-induced colitis in mice after systemic administration, and its anti-inflammatory action is associated with mu and kappa opioid receptors.


CONCLUSIONS
We show that indirect stimulation of opioid receptors by the blockade of NEP and APN is a promising pharmacological strategy for the treatment of IBD, and may become of greater importance than the use of classical opioid agonists.
Department Biochemistry, Medical University of Lodz, Lodz, Poland.
M
M
Salaga
Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.
A
A
Mokrowiecka
Department of Cytobiochemistry, University of Lodz, Lodz, Poland.
D
D
Jacenik
Department of Molecular Biotechnology, University of Gdansk, Gdansk, Poland.
A I
AI
Cygankiewicz
Department of Digestive Tract Diseases, Medical University of Lodz, Lodz, Poland.
E
E
Malecka-Panas
Department of Pathology, Faculty of Medicine,Lodz, Poland.
R
R
Kordek
Department of Cytobiochemistry, University of Lodz, Lodz, Poland.
W M
WM
Krajewska
Department of Molecular Biotechnology, University of Gdansk, Gdansk, Poland.
M K
MK
Sobocinska
Department of Molecular Biotechnology, University of Gdansk, Gdansk, Poland.
E
E
Kamysz
Department Biochemistry, Medical University of Lodz, Lodz, Poland.
J
J
Fichna
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D003092:Colitis / Q000188:drug therapy*; D004195:Disease Models, Animal; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010455:Peptides / Q000008:administration & dosage*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010455:Peptides; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C000627424:sialorphin
Inflammatory bowel diseases; aminopeptidase N; sialorphin