Nitroxide radical attenuates ischaemia/reperfusion injury to therat small intestine

Background—Free radicals are associated withpost-ischaemic intestinal injury and contribute to major clinicalproblems primarily in premature infants. Various antioxidative meansand modes of intervention, previously tested, have demonstrated onlylimited efficacy.
Aims—To study the protective activity of thestable nitroxide radical 4-OH, 2,2,6,6-tetramethylpiperidine-1-oxyl(TPL) and its respective hydroxylamine (TPL-H) againstischaemia/reperfusion (I/R) injury.
Methods—An isolated loop of ileum was created inlaboratory male Sabra rats and constantly perfused with warmed normalsaline. Intestinal injury was elicited through clamping of the superior mesenteric rat artery followed by reperfusion. Either TPL or TPL-H wasgiven intravenously immediately before ischaemia or reperfusion andcontinuously afterwards. The rate of mucosal to lumen clearance ofpara-aminohippurate (PAH) was used to evaluate intestinal mucosal injury. Serum and perfusate levels of both TPL and TPL-H were measuredusing electron paramagnetic resonance spectrometry.
Results—The increase in intestinal permeabilityinduced by I/R was significantly inhibited by both TPL and TPL-H. Thenitroxide was effective also when given immediately before reperfusion.
Conclusion—Through a continuous exchange, TPL andTPL-H act as self-replenishing antioxidants and thus protect fromintestinal injury. This demonstrates the potential of the family ofnitroxide antioxidants against oxidative stress in general and I/Rinjury in particular.

Keywords:intestinal mucosa; oxidative damage; free radicals; spin labels; antioxidants