Protection of carbon monoxide intraperitoneal administration from rat intestine injury induced by lipopolysaccharide.
BACKGROUND
Treatment with inhaled carbon monoxide (CO) has been shown to ameliorate intestinal injury in experimental animals induced by lipopolysaccharide (LPS) or ischemia-reperfusion. We hypothesized that CO intraperitoneal administration (i.p.) might provide similar protection to inhaled gas. This study aimed to investigate the effects of continuous 2 L/min of 250 ppm CO i.p. on rat intestine injury induced by LPS and to try to develop a more practical means of delivering the gas.


METHODS
A total of 72 male Sprague-Dawley rats were randomly assigned to 4 groups: control group, CO i.p. group, LPS group and LPS+CO i.p. group. One hour after intravenously received 5 mg/kg LPS, the rats in LPS group and LPS+CO i.p. group were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively, and the rats of control group and CO i.p. group intravenously received an equal volume of 0.9% NaCl and 1 hour later, were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively. One, 3 and 6 hour of each group after treated with room air or CO i.p., the animals (n = 6 for each time point) were sacrificed and intestinal tissues were collected for determinating the levels of platelet activator factor (PAF) and intercellular adhesion molecule-1 (ICAM-1) with enzyme-lined immunosorbent assays. The maleic dialdehyde (MDA) content and the myeloperoxidase (MPO) activity were determined with a chemical method. The phosphorylated p38 mitogen activated protein kinase (MAPK) expression was assayed with Western blotting and the cell apoptotic rate with flow cytometery. The arterial oxygenation was measured by blood gas analysis, and the pathology determined by light microscope.


RESULTS
After treatment with 2 L/min of 250 ppm CO i.p., the increase of PAF, ICAM-1, MDA, MPO, and cell apoptotic rate induced by LPS was markedly reduced (P < 0.05 or 0.01), and accompanied by ameliorating intestine injury. Western blotting showed that these effects of CO i.p. were mediated by p38 MAPK pathway. There were no significant differences in all observed parameters between control group and CO i.p. group.


CONCLUSIONS
The injury to the intestine via anti-oxidant, anti-inflammation and anti-apoptosis, which may involve the p38 MAPK pathway, was induced by 2 L/min of 250 ppm CO i.p. exerting potent protection against LPS.
Liu
Shao-hua
SH
First Affiliated Hospital of Nanjing Medicial University, Jiangsu, China. liush67@hotmail.com
Ma
Ke
K
Xu
Bing
B
Xu
Xin-rong
XR
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D005434:Flow Cytometry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects* / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008853:Microscopy; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000139:chemically induced / Q000188:drug therapy; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000447:Aldehydes; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D018799:Intercellular Adhesion Molecule-1; C015977:malealdehyde; D002248:Carbon Monoxide; D009195:Peroxidase; D048051:p38 Mitogen-Activated Protein Kinases