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Cytoprotection by diclofenac sodium after intestinal ischemia/reperfusion injury
D J Schmeling1, M G Caty, K T Oldham
1Department of Surgery, Duke University Medical Center, Durham, NC 27710.
Insights
Diclofenac sodium (DS) significantly protects the intestine from ischemia/reperfusion (I/R) injury by preserving ATP levels. This cytoprotective effect surpasses traditional antioxidants and does not involve preventing neutrophil influx.
Area of Science:
- Pediatric Surgery
- Gastroenterology
- Pharmacology
Background:
- Intestinal ischemia/reperfusion (I/R) injury is a critical concern in pediatric surgery.
- I/R injury involves impaired oxygen delivery and subsequent inflammation.
- Neutrophils and oxidants play a key role in secondary inflammatory responses.
Purpose of the Study:
- To evaluate diclofenac sodium (DS), a nonsteroidal anti-inflammatory agent, for treating intestinal I/R injury.
- To compare the efficacy of DS with conventional antioxidants in mitigating I/R injury.
- To investigate the mechanism of DS in preventing intestinal tissue damage.
Main Methods:
- Rats underwent intestinal ischemia followed by reperfusion.
- Intestinal myeloperoxidase (MPO) levels were measured to assess neutrophil sequestration.
- Adenosine triphosphate (ATP) content was analyzed as a marker of tissue injury.
Main Results:
- I/R injury led to significant neutrophil sequestration and ATP depletion in the intestine.
- Diclofenac sodium (DS) pretreatment did not inhibit neutrophil sequestration.
- DS significantly attenuated ATP depletion, demonstrating a cytoprotective effect.
- The ATP preservation by DS exceeded that of conventional antioxidants like xanthine-oxidase inhibitors and superoxide dismutase.
Conclusions:
- Diclofenac sodium (DS) exhibits a significant cytoprotective effect against intestinal I/R injury.
- DS preserves intestinal ATP levels more effectively than traditional antioxidants.
- The protective mechanism of DS does not involve the prevention of neutrophil influx into the injured intestine.
Abstract:
Intestinal injury resulting from ischemia/reperfusion (I/R) is of fundamental importance in clinical pediatric surgery. I/R injury results from inadequate oxygen delivery as well as a secondary inflammatory response involving neutrophils and oxidants. This study was designed to evaluate a novel use for diclofenac sodium (DS), a nonsteroidal antiinflammatory agent, and to compare it with traditional antioxidants in this setting. Rats were subjected to intestinal ischemia followed by reperfusion. When killed, samples were obtained for measurement of intestinal myeloperoxidase (MPO), a measure of neutrophil sequestration, as well as for adenosine triphosphate (ATP) content, a marker of tissue injury. Animals exposed to I/R injury had significant neutrophil sequestration in the intestine by 120 minutes of ischemia, and this persisted after 60 minutes of reperfusion. DS pretreatment did not prevent neutrophil sequestration in the intestine. Analysis of intestinal ATP content demonstrated a decrease in intestinal ATP after 120 minutes of ischemia, and this did not change with 60 minutes of reperfusion. Pretreatment with DS significantly attenuated this intestinal ATP depletion. Furthermore, with 120 minutes of ischemia and 60 minutes of reperfusion, ATP preservation with DS pretreatment exceeded that obtained using the following conventional antioxidants: a xanthine-oxidase inhibitor (lodoxamide), deferoxamine, dimethysulfoxide, and superoxide dismutase plus catalase. DS has a significant cytoprotective effect for intestine subjected to I/R injury, exceeding that of conventional antioxidants. DS does not attenuate injury by preventing neutrophil influx into injured intestine.(ABSTRACT TRUNCATED AT 250 WORDS)