Is a toxic gas protecting the liver?

The liver is the primary organ involved in heme detoxification under disease conditions, but its self-protective mechanisms against toxic compounds are unknown. In the April Gastroenterology Takanori Kyokane and colleagues from Nagoya University School of Medicine, Nagoya, suggest that carbon monoxide (CO), the gaseous product of heme oxygenase (HO), may have a protective role against hepatobiliary dysfunction caused by heme overloading under sepsis and stress conditions.

Kyokane et al perfused livers of endotoxin pre-treated rats with HbO₂, which captures nitric oxide (NO) and CO, or with metHb, a reagent trapping NO but not CO. The rats treated with HbO₂ showed a marked vasoconstriction and cholestasis that was not reproduced by administration of metHb.

In addition, CO supplementation attenuated the vasoconstriction and cholestasis caused by coadministration of aminoguanidine (an NO synthase inhibitor) and zinc protoporphyrin-IX (an HO inhibitor). This suggests that CO is hepatoprotective and that simultaneous...