Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion

Emanuela Masini, Salvatore Cuzzocrea, Emanuela Mazzon, Carmelo Muià, Alfredo Vannacci, Francesca Fabrizi, Daniele Bani

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

1 Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and inflammation which contribute to the pathophysiology of shock. We investigated the effects of relaxin (RLX), known to afford protection against the deleterious effects of cardiac ischemia/reperfusion, given to rats subjected to splanchnic artery occlusion and reperfusion (SAO/R)-induced splanchnic injury. 2 RLX (30 ng kg -1, 15 min. before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/R. RLX also reduced histopathological changes, leukocyte infiltration (myeloperoxidase) and expression of endothelial cell adhesion molecules in the ileum. RLX counteracted free radical-mediated tissue injury, as judged by significant decrease in the tissue levels of peroxidation and nitration products (malondialdehyde, nitrotyrosine), DNA damage markers (8-hydroxy-2′- deoxyguanosine, poly-ADP-ribosylated DNA) and consumption of tissue antioxidant enzymes (superoxide dismutase). As a result, RLX led to a reduction of ileal cell apoptosis (caspase 3, terminal deoxynucleotidyltransferase-mediated UTP end labeling). The effects of RLX appear specific, as inactivated RLX substituted for the bioactive hormone had no effects. 3 In conclusion, these results show that RLX exerts a clear-cut protective effect in SAO/R-induced splanchnic injury, likely due to endothelial protection, decreased leukocyte recruitment and hindrance of free radical-mediated tissue injury leading to cell death, lethal complications and high mortality rate. Thus, RLX could be used therapeutically in intestinal ischemia.

Original languageEnglish
Pages (from-to)1124-1132
Number of pages9
JournalBritish Journal of Pharmacology
Volume148
Issue number8
DOIs
Publication statusPublished - Aug 24 2006

Fingerprint

Relaxin
Viscera
Reperfusion
Ischemia
Arteries
Wounds and Injuries
Free Radicals
Leukocytes
Uridine Triphosphate
DNA Nucleotidylexotransferase
Mortality
Cell Adhesion Molecules
Malondialdehyde
Genetic Markers
Ileum
Caspase 3
Adenosine Diphosphate
Peroxidase
DNA Damage
Superoxide Dismutase

Keywords

  • Apoptosis
  • Endothelial cell adhesion molecules
  • Oxygen-free radicals
  • Relaxin
  • Splanchnic artery occlusion

ASJC Scopus subject areas

  • Pharmacology

Cite this

Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion. / Masini, Emanuela; Cuzzocrea, Salvatore; Mazzon, Emanuela; Muià, Carmelo; Vannacci, Alfredo; Fabrizi, Francesca; Bani, Daniele.

In: British Journal of Pharmacology, Vol. 148, No. 8, 24.08.2006, p. 1124-1132.

Research output: Contribution to journalArticle

Masini, Emanuela ; Cuzzocrea, Salvatore ; Mazzon, Emanuela ; Muià, Carmelo ; Vannacci, Alfredo ; Fabrizi, Francesca ; Bani, Daniele. / Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion. In: British Journal of Pharmacology. 2006 ; Vol. 148, No. 8. pp. 1124-1132.
@article{cb47646039874cbaa80073c93fba1cc0,
title = "Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion",
abstract = "1 Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and inflammation which contribute to the pathophysiology of shock. We investigated the effects of relaxin (RLX), known to afford protection against the deleterious effects of cardiac ischemia/reperfusion, given to rats subjected to splanchnic artery occlusion and reperfusion (SAO/R)-induced splanchnic injury. 2 RLX (30 ng kg -1, 15 min. before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/R. RLX also reduced histopathological changes, leukocyte infiltration (myeloperoxidase) and expression of endothelial cell adhesion molecules in the ileum. RLX counteracted free radical-mediated tissue injury, as judged by significant decrease in the tissue levels of peroxidation and nitration products (malondialdehyde, nitrotyrosine), DNA damage markers (8-hydroxy-2′- deoxyguanosine, poly-ADP-ribosylated DNA) and consumption of tissue antioxidant enzymes (superoxide dismutase). As a result, RLX led to a reduction of ileal cell apoptosis (caspase 3, terminal deoxynucleotidyltransferase-mediated UTP end labeling). The effects of RLX appear specific, as inactivated RLX substituted for the bioactive hormone had no effects. 3 In conclusion, these results show that RLX exerts a clear-cut protective effect in SAO/R-induced splanchnic injury, likely due to endothelial protection, decreased leukocyte recruitment and hindrance of free radical-mediated tissue injury leading to cell death, lethal complications and high mortality rate. Thus, RLX could be used therapeutically in intestinal ischemia.",
keywords = "Apoptosis, Endothelial cell adhesion molecules, Oxygen-free radicals, Relaxin, Splanchnic artery occlusion",
author = "Emanuela Masini and Salvatore Cuzzocrea and Emanuela Mazzon and Carmelo Mui{\`a} and Alfredo Vannacci and Francesca Fabrizi and Daniele Bani",
year = "2006",
month = "8",
day = "24",
doi = "10.1038/sj.bjp.0706811",
language = "English",
volume = "148",
pages = "1124--1132",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - Protective effects of relaxin in ischemia/reperfusion-induced intestinal injury due to splanchnic artery occlusion

AU - Masini, Emanuela

AU - Cuzzocrea, Salvatore

AU - Mazzon, Emanuela

AU - Muià, Carmelo

AU - Vannacci, Alfredo

AU - Fabrizi, Francesca

AU - Bani, Daniele

PY - 2006/8/24

Y1 - 2006/8/24

N2 - 1 Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and inflammation which contribute to the pathophysiology of shock. We investigated the effects of relaxin (RLX), known to afford protection against the deleterious effects of cardiac ischemia/reperfusion, given to rats subjected to splanchnic artery occlusion and reperfusion (SAO/R)-induced splanchnic injury. 2 RLX (30 ng kg -1, 15 min. before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/R. RLX also reduced histopathological changes, leukocyte infiltration (myeloperoxidase) and expression of endothelial cell adhesion molecules in the ileum. RLX counteracted free radical-mediated tissue injury, as judged by significant decrease in the tissue levels of peroxidation and nitration products (malondialdehyde, nitrotyrosine), DNA damage markers (8-hydroxy-2′- deoxyguanosine, poly-ADP-ribosylated DNA) and consumption of tissue antioxidant enzymes (superoxide dismutase). As a result, RLX led to a reduction of ileal cell apoptosis (caspase 3, terminal deoxynucleotidyltransferase-mediated UTP end labeling). The effects of RLX appear specific, as inactivated RLX substituted for the bioactive hormone had no effects. 3 In conclusion, these results show that RLX exerts a clear-cut protective effect in SAO/R-induced splanchnic injury, likely due to endothelial protection, decreased leukocyte recruitment and hindrance of free radical-mediated tissue injury leading to cell death, lethal complications and high mortality rate. Thus, RLX could be used therapeutically in intestinal ischemia.

AB - 1 Splanchnic artery occlusion (SAO) followed by reperfusion causes endothelial injury and inflammation which contribute to the pathophysiology of shock. We investigated the effects of relaxin (RLX), known to afford protection against the deleterious effects of cardiac ischemia/reperfusion, given to rats subjected to splanchnic artery occlusion and reperfusion (SAO/R)-induced splanchnic injury. 2 RLX (30 ng kg -1, 15 min. before reperfusion) significantly reduced the drop of blood pressure and high mortality rate caused by SAO/R. RLX also reduced histopathological changes, leukocyte infiltration (myeloperoxidase) and expression of endothelial cell adhesion molecules in the ileum. RLX counteracted free radical-mediated tissue injury, as judged by significant decrease in the tissue levels of peroxidation and nitration products (malondialdehyde, nitrotyrosine), DNA damage markers (8-hydroxy-2′- deoxyguanosine, poly-ADP-ribosylated DNA) and consumption of tissue antioxidant enzymes (superoxide dismutase). As a result, RLX led to a reduction of ileal cell apoptosis (caspase 3, terminal deoxynucleotidyltransferase-mediated UTP end labeling). The effects of RLX appear specific, as inactivated RLX substituted for the bioactive hormone had no effects. 3 In conclusion, these results show that RLX exerts a clear-cut protective effect in SAO/R-induced splanchnic injury, likely due to endothelial protection, decreased leukocyte recruitment and hindrance of free radical-mediated tissue injury leading to cell death, lethal complications and high mortality rate. Thus, RLX could be used therapeutically in intestinal ischemia.

KW - Apoptosis

KW - Endothelial cell adhesion molecules

KW - Oxygen-free radicals

KW - Relaxin

KW - Splanchnic artery occlusion

UR - http://www.scopus.com/inward/record.url?scp=33747133303&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747133303&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0706811

DO - 10.1038/sj.bjp.0706811

M3 - Article

VL - 148

SP - 1124

EP - 1132

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 8

ER -