Anesthetics and natural heme oxygenase-1 inducers: waiting for carbon monoxide?

In their report the authors showed that isoflurane anesthesia leads to increased expression of HO-1 in the liver and suggest that this leads to in- creased protection from ischemic injury. We agree with the authors’ conclusion and would like to add that there are well- characterized natural compounds that in- crease HO-1 expression and could there- fore be used as adjuvant therapy following ischemia-reperfusion injury. Nontoxic polyphenols can act as potent inducers of HO-1 expression in the liver, which could account for the observed organ preserva- tion. In particular, curcumin induces HO-1 expression in human hepatocytes during the cold storage and rewarming period, and is cytoprotective against oxidative in- jury.2 Another natural compound that in- duces HO-1 expression is cyanidin-3-O- -glucoside, an anthocyanin with marked antioxidant properties.3 In animal models of ischemia-reperfusion challenges, cyani- din-3-O- -glucoside has a protective ef- fect in the liver.4–6 In this context, propofol, a poly- phenolic compound that is widely used as an anesthetic, has been shown to induce HO-1 expression at clinically rel- evant concentrations. To this regard, we showed that propofol induces HO-1 via an NFkB-mediated pathway and that the protective effects of HO-1 are abolished in part by SnMP, a well known inhibitor of HO activity.7 Due to its phenolic nature, this latter compound could pro- vide additional protection by acting also as a reactive oxygen species scavenger, thus improving the allograft outcome. Consistently with these observations, Wang et al showed that propofol in- duces HO-1 mRNA expression in the kidney following 2 hours of reperfusion, which may account for the observed improved organ function.8Total intravenous anesthesia has been considered for use in liver transplan- tation, but this technique, as well as the gaseous anesthesia, presents some disad- vantages and limitations. It is worth noting that both isoflurane and propofol induce HO-1 expression via the NFkB pathway;