The non-metabolizable organic
anion indocyanine green (ICG) has been shown previously to reduce markedly the biliary secretion of
acetaminophen, particularly the
glutathione conjugate of
APAP (
APAP-GSH), suggesting that this
APAP metabolite may compete with other
xenobiotics for excretion into the bile via a canalicular organic
anion transport process. This study was conducted to determine whether changes in the biliary disposition of
APAP induced by ICG could lead to alterations in susceptibility to
APAP hepatotoxicity. To investigate this, groups of overnight-fasted male CD-1 mice received 30 micromol ICG/kg, intravenously, immediately prior to
APAP dosing (500 mg/kg, ip). Controls were given
propylene glycol vehicle. Mice were killed at 4 h after
APAP challenge for immunochemical analysis of cytosolic
protein arylation and determination of non-
protein sulfhydryl (NPSH) depletion, or at 12 and 24 h for biochemical and histological assessment of liver injury. Elevated plasma
sorbitol dehydrogenase activity and centrilobular hepatocellular
necrosis was present in control mice receiving
APAP at 12 and 24 h. Treatment with ICG did not alter susceptibility to
APAP toxicity when measured at 12 h after challenge. However, the severity of histologic lesions in the ICG-
APAP group was significantly lower at 24 h after challenge. Furthermore, treatment with ICG did not alter
APAP-induced
glutathione depletion or cytosolic
protein arylation. These data suggest that the organic
anion ICG has a protective effect on
APAP toxicity that promotes a faster recovery from liver injury.