Related Experiment Video
Updated: May 5, 2026
Ischemia-reperfusion Model of Acute Kidney Injury and Post Injury Fibrosis in Mice
Published on: August 9, 2013
Alpha-melanocyte-stimulating hormone protects against renal injury after ischemia in mice and rats
1Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8856, USA.
Abstract:
Reperfusion after ischemia induces cytokines, chemoattractant chemokines, adhesion molecules, and nitric oxide (NO). The resultant neutrophil adherence and NO potentiates renal injury. alpha-Melanocyte-stimulating hormone (alpha-MSH) is a potent anti-inflammatory agent that inhibits neutrophil migration and production of neutrophil chemokines and NO. Since neutrophils and NO promote renal ischemic injury, we sought to determine if alpha-MSH inhibits renal injury in a model of bilateral renal ischemia. alpha-MSH significantly reduced ischemia-induced renal damage, measured by changes in renal histology and plasma blood urea nitrogen and creatinine in mice. alpha-MSH significantly decreased tubule necrosis, neutrophil plugging, and capillary congestion. Delay of alpha-MSH treatment for 6 h after ischemia also significantly inhibited renal damage. alpha-MSH also significantly inhibited ischemic damage in rats. To begin to determine the mechanism of action of alpha-MSH, we measured its effects on mediators of neutrophil trafficking and induction of the inducible isoform of NO synthase-II. alpha-MSH inhibited ischemia-induced increases in mRNA for the murine neutrophil chemokine KC/IL-8. alpha-MSH also inhibited induction of mRNA for the adhesion molecule ICAM-1, which is known to be critical in renal ischemic injury. alpha-MSH inhibited nitration of kidney proteins and induction of NO synthase-II. We conclude: (a) alpha-MSH protects against renal ischemia/reperfusion injury; and (b) it may act, in part, by inhibiting the maladaptive activation of genes that cause neutrophil activation and adhesion, and induction of NO synthase.
Insights
Alpha-Melanocyte-stimulating hormone (alpha-MSH) effectively reduces kidney damage from ischemia and reperfusion. This potent anti-inflammatory agent inhibits neutrophil activity and nitric oxide (NO) production, crucial factors in renal injury.
Area of Science:
- Renal physiology
- Inflammation research
- Endocrinology
Background:
- Ischemia-reperfusion injury (IRI) triggers inflammatory responses, including cytokine release, chemokine production, and adhesion molecule upregulation.
- Neutrophil infiltration and nitric oxide (NO) synthesis exacerbate renal damage during IRI.
- Alpha-Melanocyte-stimulating hormone (alpha-MSH) exhibits anti-inflammatory properties, suppressing neutrophil migration and chemokine generation.
Purpose of the Study:
- To investigate the protective effects of alpha-MSH against renal IRI in a bilateral ischemia model.
- To elucidate the mechanisms by which alpha-MSH mitigates renal injury.
Main Methods:
- Administration of alpha-MSH in mouse and rat models of bilateral renal ischemia.
- Assessment of renal damage via histological examination and plasma markers (blood urea nitrogen, creatinine).
- Measurement of gene expression for neutrophil chemokines (KC/IL-8) and adhesion molecules (ICAM-1), and analysis of NO synthase-II induction and protein nitration.
Main Results:
- Alpha-MSH significantly attenuated renal damage, reducing tubule necrosis, neutrophil plugging, and capillary congestion.
- Delayed administration of alpha-MSH also demonstrated significant protective effects.
- Alpha-MSH inhibited ischemia-induced increases in KC/IL-8 and ICAM-1 mRNA, suppressed NO synthase-II induction, and reduced protein nitration.
Conclusions:
- Alpha-MSH confers significant protection against renal ischemia/reperfusion injury.
- The protective mechanism involves the inhibition of maladaptive inflammatory gene activation, including those related to neutrophil recruitment and NO synthesis.
