Glycogen synthase kinase-3β (GSK3β) is a serine/threonine protein kinase that plays an important role in renal tubular injury and regeneration in acute kidney injury. However, its role in the development of renal fibrosis, often a long-term consequence of acute kidney injury, is unknown. Using amousemodel of renal fibrosis induced by ischemia-reperfusion injury, we demonstrate increased GSK3β e...

With the advances in percutaneous coronary intervention technology and accompanying medical therapy, the prognosis of patients with acute coronary syndromes has greatly improved over the last decades. Still, approximately 6% of admitted patients do not survive to hospital discharge,1 and despite the implementation of rapid interventional protocols, loss of cardiac tissue, and a consecutive decr...

3. Li Volti G, Sorrenti V, Murabito P et al. Pharmacological induction of heme oxygenase-1 inhibits iNOS and oxidative stress in renal ischemiareperfusion injury. Transplant Proc 2007; 39: 2986–2991 4. Datta PK, Koukouritaki SB, Hopp KA et al. Heme oxygenase-1 induction attenuates inducible nitric oxide synthase expression and proteinuria in glomerulonephritis. J Am Soc Nephrol 1999; 10: 2540–2...

We read with interest the study by Christiansen and colleagues [1] in the previous issue of Critical Care. In a large cohort study, the authors report that among diabetic patients who are admitted to the ICU, the preadmission use of metformin is associated with a lower mortality rate. Here, we highlight that metformin limits ischemiareperfusion injury (IRI) and modulates inflammation by increas...

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily that regulate the expression of genes involved in a variety of biological processes, including lipid metabolism and insulin sensitivity. Members of the PPAR family—in particular, PPAR—have more recently been shown to broadly regulate inflammatory and reparative responses. PPARis expressed...

Early reperfusion of the ischemic myocardium has been shown to reduce mortality in acute myocardial infarction. Unfortunately, reperfusion, although necessary to relieve ischemia, may be followed by morphological, functional, and electrical changes that result in additional myocardial damage, known as reperfusion injury. In animal models, several pharmacologic agents and reperfusion strategies ...

Carbon monoxide (CO) and hydrogen sulfide (H2S) are small, lipid-soluble gaseous autacoids that modulate numerous physiological processes. Historically, both gases were considered highly noxious environmental hazards having well-defined modes of toxicity: CO binds avidly to hemoglobin reducing the oxygen-carrying capacity of the protein leading to tissue hypoxia while H2S is a potent mitochondr...

Remote ischemic preconditioning (RIPC) is an intrinsic phenomenon whereby 3~4 consecutive ischemia-reperfusion cycles to a remote tissue (noncardiac) increases the tolerance of the myocardium to sustained ischemiareperfusion induced injury. Remote ischemic preconditioning induces the local release of chemical mediators which activate the sensory nerve endings to convey signals to the brain. The...

EVEN BEFORE the endothelium-derived relaxing factor (EDRF) was known to be nitric oxide (NO), it was recognized that it could be inactivated by the radical superoxide (O2 · ) (16). Once the EDRF was identified as NO, the chemistry underlying this phenomenon was obvious. Both NO and O2 · are radicals, and rapidly react with one another to form the strong oxidant peroxynitrite, which ultimately d...

Porter GA, Urciuoli WR, Brookes PS, Nadtochiy SM. SIRT3 deficiency exacerbates ischemia-reperfusion injury: implication for aged hearts. Am J Physiol Heart Circ Physiol 306: H1602–H1609, 2014. First published April 18, 2014; doi:10.1152/ajpheart.00027.2014.—Ischemiareperfusion (IR) injury is significantly worse in aged hearts, but the underlying mechanisms are poorly understood. Age-related dam...