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Updated: Jun 17, 2026
Method of Direct Segmental Intra-hepatic Delivery Using a Rat Liver Hilar Clamp Model
Published on: April 2, 2017
Liver X receptor agonist treatment reduced splanchnic ischemia and reperfusion injury
Concetta Crisafulli1, Rosanna Di Paola, Emanuela Mazzon
1Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, 98100 Messina, Italy.
Abstract:
LXR is another member of the superfamily of nuclear hormone receptors that heterodimerizes with RXR and regulates the intracellular levels of cholesterol through gene induction of enzymes and proteins involved in the cholesterol metabolism and transport. LXR ligands inhibit the gene expression of proinflammatory mediators in immunostimulated macrophages; in vivo studies have shown that activation of LXR reduces the inflammatory response in a murine model of contact dermatitis and atherosclerosis. No reports have addressed a role for LXRs in pathophysiology of intestinal ischemia. The aim of this study was to investigate the effects of T0901317, a potent LXR ligand, in a mouse model of SAO shock, which was induced by clamping the superior mesenteric artery and the celiac trunk, resulting in a total occlusion of these arteries for 30 min. After this period of occlusion, the clamps were removed. Mice were killed at 60 min after reperfusion. This study provides the evidence that T0901317, LXR agonist, modulates: the development of SAO shock; the infiltration of the tissue with PMNs; the expression of TNF-alpha and IL-1beta; the nitration of tyrosine residues; NF-kappaB expression; the MAPK phosphorylation (ERK, JNK, and p38); FasL; apoptosis; Bax and Bcl-2 expression; and the degree of tissue injury caused by SAO shock. Our results imply that LXR agonists may be useful in the therapy of inflammation.
Insights
Liver X Receptor (LXR) agonists, like T0901317, show potential in treating intestinal ischemia by reducing inflammation and tissue damage. This study investigated LXR
Area of Science:
- Molecular Biology
- Immunology
- Pathophysiology
Background:
- Liver X Receptors (LXRs) are nuclear receptors regulating cholesterol metabolism.
- LXR ligands are known to inhibit inflammatory gene expression in macrophages.
- The role of LXRs in intestinal ischemia pathophysiology remains unexplored.
Purpose of the Study:
- To investigate the therapeutic effects of the LXR ligand T0901317 in a mouse model of superior mesenteric artery (SMA) occlusion shock.
- To evaluate LXR agonist's impact on inflammatory markers and tissue injury.
Main Methods:
- Induction of SMA occlusion shock in mice by clamping superior mesenteric artery and celiac trunk for 30 minutes.
- Administration of T0901317, a potent LXR agonist.
- Assessment of inflammatory cell infiltration, cytokine expression (TNF-alpha, IL-1beta), NF-kappaB activation, MAPK phosphorylation, apoptosis, and tissue damage post-reperfusion.
Main Results:
- T0901317 significantly modulated the development of SMA occlusion shock.
- LXR activation reduced polymorphonuclear neutrophil (PMN) infiltration, pro-inflammatory cytokine expression, and tyrosine nitration.
- T0901317 suppressed NF-kappaB expression, MAPK phosphorylation, FasL, and apoptosis, while altering Bax and Bcl-2 expression, ultimately reducing tissue injury.
Conclusions:
- LXR agonists, exemplified by T0901317, demonstrate a protective role in a mouse model of intestinal ischemia.
- Modulation of inflammatory pathways and apoptosis by LXR activation suggests potential therapeutic applications for intestinal ischemia and related inflammatory conditions.
