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2016 ; 45
(4
): 359-66
Nephropedia Template TP
gab.com Text
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SIRTUIN 1 ACTIVATOR SRT1720 PROTECTS AGAINST ORGAN INJURY INDUCED BY INTESTINAL
ISCHEMIA-REPERFUSION
#MMPMID26263437
Hansen LW
; Khader A
; Yang WL
; Prince JM
; Nicastro JM
; Coppa GF
; Wang P
Shock
2016[Apr]; 45
(4
): 359-66
PMID26263437
show ga
Intestinal ischemia-reperfusion (I/R) occurs in various clinical situations and
causes local and remote organ injury, especially in the lungs, leading to
significant morbidity and mortality. The maintenance of mitochondrial biogenesis
is essential for cell survival and is regulated in part by sirtuin 1 (SIRT1), an
energy-sensing enzyme. We hypothesized that SIRT1 activation with SRT1720 would
reduce local and remote organ injury after intestinal I/R. Intestinal I/R was
induced by the occlusion of the superior mesenteric artery of adult male C57BL/6
mice for 45?min, followed by reperfusion for 4?h. SRT1720 or vehicle was injected
intravenously at the time of reperfusion. Blood, small intestine, and lung
tissues were collected for analysis. The SRT1720 treatment of I/R mice resulted
in a 57% increase in protein levels of succinate dehydrogenase, an index of
mitochondrial mass, and a 120% increase in messenger RNA levels of mitochondrial
transcription factor A, a marker for mitochondrial biogenesis. The microscopic
architecture and apoptosis of the gut tissue was improved in the SRT1720-treated
I/R mice. SRT1720 decreased intestinal messenger RNA levels of tumor necrosis
factor-? by 60% and inducible nitric oxide synthase to baseline after I/R.
Systemic inflammation, as determined by serum interleukin-6, was reduced in
treated mice. Lung injury, as measured by histological architecture and
myeloperoxidase activity, and lung apoptosis were also improved after the SRT1720
treatment. SRT1720 preserved mitochondrial biogenesis and mass, leading to
inhibition of inflammation and oxidative stress, thereby protecting against
intestinal I/R-induced injury. Thus, the SIRT1-mediated pathway is a promising
target for the treatment of intestinal I/R injury.
|Animals
[MESH]
|Enzyme Activators/*pharmacology
[MESH]
|Heterocyclic Compounds, 4 or More Rings/*pharmacology
[MESH]
|Intestinal Diseases/enzymology/pathology/*prevention & control
[MESH]