Effects of choline treatment in concentrations of serum matrix metalloproteinases (MMPs), MMP tissue inhibitors (TIMPs) and immunoglobulins in an experimental model of canine sepsis.
The aim of the present study was to investigate effects of intravenous (i.v.) choline treatment on serum matrix metalloproteinases (MMP), MMP tissue inhibitors (TIMP) and immunoglobulins (Igs), and to determine if there were relations between serum MMPs/TIMPs and C-reactive protein (CRP) (as a marker of the acute phase response), immunoglobulin G and M (IgG and IgM) (as a maker of the Ig responses) and markers of organ damage such as muscular damage (creatine phosphokinase, [CPK]), liver damage (alanine aminotransferase [ALT]) and renal dysfunction (blood urea nitrogen [BUN] and creatinine, [Cr]) in dogs with endotoxemia. Healthy dogs (n=24) were randomized to Saline, Choline (C), Lipopolysaccharide (LPS), and LPS+C groups and received 0.9% NaCl (5mL/i.v.), choline chloride (20mg/kg/i.v.), LPS (0.02mg/kg/i.v.) and LPS (0.02mg/kg/i.v.) plus choline chloride (20mg/kg/i.v.), respectively. Serum MMPs and TIMPs concentrations were analyzed by commercial ELISA kits. MMP and TIMP increased at 1-48h (P<0.05), whereas IgG and IgM decreased at 24-48h in LPS group, compared to their baselines. Choline treatment reduced changes in serum MMPs, TIMPs and markers of organ damage, and prevented the hypoimmunoglobulinemia in LPS+C. MMPs and TIMPs were correlated positively (P<0.05) with serum CRP, CPK, ALT, BUN and Cr, but not with serum Igs. Our findings suggest that the serum MMPs, TIMPs and Igs are involved in the pathophysiology of endotoxemia, and MMPs and TIMPs are correlated with the acute phase reaction and multi-organ failure. In addition, we demonstrated a direct effect of choline administration in decreasing serum MMPs and TIMPs, and preserving serum Igs in the course of endotoxemia.
Department of Internal Medicine, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey. Electronic address: merick@uludag.edu.tr.
Meric
M
Kocaturk
Medical-Surgical Research Center, Agricultural Faculty, Osmangazi University Eskişehir, Turkey. Electronic address: oya.eralp@gmail.com.
Oya
O
Eralp-Inan
Departament de Medicina i Cirurgia Animals, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain. Electronic address: asta@um.es.
A
A
Tvarijonaviciute
Department of Pharmacology, Medical Faculty, Uludag University, Bursa, Turkey. Electronic address: mcansev@uludag.edu.tr.
Mehmet
M
Cansev
Department of Veterinary Pathology, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey. Electronic address: ozyigit@uludag.edu.tr.
M Ozgur
MO
Ozyigit
Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, 30100 Espinardo, Murcia, Spain. Electronic address: jjceron@um.es.
J J
JJ
Ceron
Department of Internal Medicine, Faculty of Veterinary Medicine, Uludag University, Bursa 16059, Turkey. Electronic address: zyilmaz@uludag.edu.tr.
Zeki
Z
Yilmaz
Department of Veterinary Pathology, Faculty of Veterinary Medicine, Uludag University, Bursa, Turkey.
M Mufit
MM
Kahraman
D000818:Animals; D002097:C-Reactive Protein / Q000032:analysis; D002794:Choline / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004285:Dogs; D019446:Endotoxemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D020782:Matrix Metalloproteinases / Q000097:blood*; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*
D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019714:Tissue Inhibitor of Metalloproteinases; D002097:C-Reactive Protein; D020782:Matrix Metalloproteinases; D002794:Choline
Choline; Dog; Endotoxemia; Immunoglobulin; Matrix metalloproteinase; Sepsis