Related Experiment Video
Updated: Jun 23, 2026
Murine Model of Intestinal Ischemia-reperfusion Injury
Published on: May 11, 2016
Nitroxide radical attenuates ischaemia/reperfusion injury to the rat small intestine
R Udassin1, Y Haskel, A Samuni
1Department of Pediatric Surgery, Hadassah University Hospital Mount Scopus, Jerusalem, Israel.
Insights
Stable nitroxide radicals, 4-OH, 2,2,6,6-tetramethylpiperidine-1-oxyl (TPL) and its hydroxylamine (TPL-H), effectively protect against post-ischaemic intestinal injury. These antioxidants demonstrate potential for treating oxidative stress and reperfusion injury.
Area of Science:
- Biomedical Science
- Pharmacology
- Gastroenterology
Background:
- Free radicals contribute to post-ischaemic intestinal injury, a significant clinical issue, especially in premature infants.
- Previous antioxidant interventions have shown limited efficacy in mitigating this injury.
Purpose of the Study:
- To investigate the protective effects of the nitroxide radical TPL and its hydroxylamine TPL-H against intestinal ischaemia/reperfusion (I/R) injury.
- To assess the potential of nitroxide antioxidants in managing oxidative stress-related conditions.
Main Methods:
- An isolated rat ileum model was used to induce and study I/R injury.
- Intestinal permeability was measured using para-aminohippurate (PAH) clearance.
- TPL and TPL-H were administered intravenously before or during reperfusion and their levels monitored via electron paramagnetic resonance spectrometry.
Main Results:
- Both TPL and TPL-H significantly reduced the intestinal permeability increase caused by I/R.
- The protective effect of the nitroxide was observed even when administered immediately before reperfusion.
Conclusions:
- TPL and TPL-H function as self-replenishing antioxidants, offering protection against intestinal injury.
- Nitroxide antioxidants show promise for treating oxidative stress and I/R injury in clinical settings.
Background:
Free radicals are associated with post-ischaemic intestinal injury and contribute to major clinical problems primarily in premature infants. Various antioxidative means and modes of intervention, previously tested, have demonstrated only limited efficacy.
Aims:
To study the protective activity of the stable nitroxide radical 4-OH, 2,2,6,6-tetramethylpiperidine-1-oxyl (TPL) and its respective hydroxylamine (TPL-H) against ischaemia/reperfusion (I/R) injury.
Methods:
An isolated loop of ileum was created in laboratory male Sabra rats and constantly perfused with warmed normal saline. Intestinal injury was elicited through clamping of the superior mesenteric rat artery followed by reperfusion. Either TPL or TPL-H was given intravenously immediately before ischaemia or reperfusion and continuously afterwards. The rate of mucosal to lumen clearance of para-aminohippurate (PAH) was used to evaluate intestinal mucosal injury. Serum and perfusate levels of both TPL and TPL-H were measured using electron paramagnetic resonance spectrometry.
Results:
The increase in intestinal permeability induced by I/R was significantly inhibited by both TPL and TPL-H. The nitroxide was effective also when given immediately before reperfusion.
Conclusions:
Through a continuous exchange, TPL and TPL-H act as self-replenishing antioxidants and thus protect from intestinal injury. This demonstrates the potential of the family of nitroxide antioxidants against oxidative stress in general and I/R injury in particular.
