title: The liver as a central regulator of hydrogen sulfide.
abstract: The liver is likely exposed to high levels of hydrogen sulfide (H2S) from endogenous hepatic synthesis and exogenous sources from the gastrointestinal tract. Little is known about the consequence of H2S exposure on the liver or hepatic regulation of H2S levels. We hypothesized that the liver has a high capacity to metabolize H2S and that H2S oxidation is decreased during sepsis, a condition in which hepatic O2 is limited and H2S synthesis is increased. Using a nonrecirculating isolated and perfused liver system, we demonstrated rapid hepatic H2S metabolism up to an infusion concentration of 200' μM H2S. Hydrogen sulfide metabolism was associated with an increase in O2 consumption from a baseline 96.7 ± 7.6 μmol O2/min/kg to 109 ± 7.4 μmol O2/min/kg at an infusion concentration of 150 μM H2S (P < 0.001). Removal of O2 from the perfusate decreased H2S clearance from a maximal 97% to only 23%. Livers isolated from rats subjected to cecal ligation and puncture (CLP) did not differ significantly from control livers in their capacity to metabolize H2S, suggesting that H2S oxidation remains a priority during sepsis. To test whether H2S induces O2 consumption in vivo, intravital microscopy was utilized to monitor the oxygen content in the hepatic microenvironment. Infusion of H2S increased the NADH/NAD+ ratio (645 gray-scale-unit increase, P = 0.035) and decreased hepatic O2 availability visualized with Ru(Phen)3(2+) (439 gray-scale-unit increase, P = 0.040). We conclude that the liver has a high hepatic capacity for H2S metabolism. Moreover, H2S oxidation consumes available oxygen and may exacerbate the tissue hypoxia associated with sepsis.
authors: Department of Biology, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA.
authors: Eric J
authors: EJ
authors: Norris
authors: Catherine R
authors: CR
authors: Culberson
authors: Sriram
authors: S
authors: Narasimhan
authors: Mark G
authors: MG
authors: Clemens
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