Pharmacokinetics and Preventive Effects of Sulfo-Albumin as a Novel Macromolecular Hydrogen Sulfide Prodrug on Carbon Tetrachloride-Induced Hepatic Injury.

Hydrogen sulfide (H2S) has been recently recognized as a gaseous signaling molecule that controls various biological activities. In the present study, we developed sulfo-albumin as a macromolecular H2S prodrug for therapeutic use, in which multisulfide groups (source of H2S) were conjugated with bovine serum albumin through a covalent linkage. In an in vitro study on H2S release in phosphate buffered saline solution, we found that H2S was released from sulfo-albumin in the presence of 5-mM glutathione but not in its absence. Furthermore, sulfo-albumin was taken up by RAW 264.7 cells, and it released H2S in cells but not in plasma. These results indicate that H2S can be selectively released from sulfo-albumin in cells. 111In-labeled sulfo-albumin predominantly accumulated in the liver, dependent upon the number of sulfide groups, after intravenous injection in mice. In a carbon tetrachloride-induced acute liver injury mouse model, sulfo-albumin significantly suppressed the increase in plasma aspartate aminotransferase and alanine aminotransferase activities, which are indicators of hepatocyte injury, after intravenous injection. These findings indicate that sulfo-albumin is a promising compound for the treatment of hepatic injuries.