Regulatory role of anesthetics on heme oxygenase-1.
As an enzyme, heme oxygenase (HO) can provide substantial cellular protection. By eliminating free heme and generating iron, biliverdin, as well as carbon monoxide, HO exerts anti-inflammatory, anti-proliferative, antioxidative, and vasodilatory effects. The inducible form of HO, heme oxygenase-1 (HO-1) can be upregulated by harmful stimuli in most human cell types. In such a way, cells utilize HO-1 as a mechanism of self-protection. Many studies have shown that upregulation of HO-1 prior to injurious stimuli conferred protection to cells and organs against subsequent injury. Therefore, manipulation of HO-1 gene expression might represent a valuable strategy for the prevention of organ dysfunction. In recent studies, intravenous and inhaled anesthetics (e.g., ketamine, propofol, opioids, isoflurane, sevoflurane, desflurane, etc.) not only upregulate HO-1 to varying extents, but account for organ protection via the HO pathway. The major advantage of anesthetics over other HO-inducing agents is related to their clinically proven safety. Another important issue is that patients receiving anesthetics in anesthesia or intensive care medicine are often suffering from pathological conditions involving pro-oxidative or pro-inflammatory states. Therefore, it would be interesting to know whether the impact of anesthetics on HO-1 regulation might influence outcome of these patients. This overview summarizes the effects of different anesthetics on HO-1 regulation and function in disease models.
Hoetzel
Alexander
A
University Medical Center Freiburg, Department of Anesthesiology and Critical Care Medicine, Freiburg, Germany. alexander.hoetzel@uniklinik-freiburg.de
Schmidt
René
R
D000777:Anesthetics / Q000494:pharmacology*; D018685:Anesthetics, Inhalation / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans
D000777:Anesthetics; D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D051547:Heme Oxygenase-1