Inosine modulates gut barrier dysfunction and end organ damage in a model of ischemia-reperfusion injury.
BACKGROUND
Gut barrier failure is an important source of morbidity in critically ill patients, and patients undergoing aortic cross-clamp. Inosine, an endogenous purine nucleoside without known side effects, formed from the breakdown of adenosine by adenosine deaminase, has been shown to modify the effects of hypoxia on various tissues, including the heart and the brain.


METHODS
This study examined the effect of inosine on ischemia-reperfusion-induced gut barrier dysfunction and on the associated lung injury. Twenty-four male Sprague-Dawley rats were divided into three groups. Eight were subjected to 60 min of superior mesenteric artery occlusion followed by 4 h of reperfusion. Eight had 100 mg/kg inosine prior to ischemia-reperfusion and 8 had sham laparotomy with encircling but not occlusion of the superior mesenteric artery.


RESULTS
Rats treated with inosine had significantly less gut barrier dysfunction. Rats subjected to SMAO sustained a substantial lung injury and this was attenuated by inosine treatment. Serum cytokine levels were also significantly lower.


CONCLUSIONS
We conclude that inosine has a beneficial effect in modulating both gut barrier dysfunction and distant organ injury in response to gut ischemia-reperfusion.
Dowdall
J F
JF
The RCSI Department of Surgery, Beaumont Hospital, Dublin, 9, Ireland. idowdall@dol.ie
Winter
D C
DC
Bouchier-Hayes
D J
DJ
D000818:Animals; D003911:Dextrans / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D007288:Inosine / Q000494:pharmacology*; D015850:Interleukin-6 / Q000097:blood; D007408:Intestinal Absorption / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D008171:Lung Diseases / Q000188:drug therapy / Q000473:pathology; D008297:Male; D017538:Mesenteric Artery, Superior; D008833:Microcirculation; D009195:Peroxidase / Q000378:metabolism; D011652:Pulmonary Circulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D003911:Dextrans; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C015219:fluorescein isothiocyanate dextran; D007288:Inosine; D009195:Peroxidase; D016650:Fluorescein-5-isothiocyanate