The effect of propylene glycol on the P450-dependent metabolism of acetaminophen and other chemicals in subcellular fractions of mouse liver

Journal Article · Fri Jan 01 00:00:00 EST 1993 · Life Sciences; (United States)

DOI:https://doi.org/10.1016/0024-3205(93)90138-S· OSTI ID:7062445

Snawder, J E; Benson, R W; Leakey, J E.A.; Roberts, D W ^[1]

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1. National Center for Toxicological Research, Jefferson, AR (United States)

Propylene glycol (PG) decreases the hepatotoxicity of acetominophen (APAP). To elucidate the mechanism for this response, the authors measured the effect of PG on the in vitro metabolism of APAP by subcellular liver fractions from 6-10 week-old male B6C3F1 mice. The fractions were assayed for their ability to bioactivate APAP to N-acetyl-p-benzoquinone imine, which was trapped as APAP-glutathione conjugates or APAP-protein adducts, and for dimethyl-nitrosamine-N-demethylase (DMN), 4-nitrophenol hydroxylase (4-NPOH), and phenacetin-O-deethylase (PAD) activities. Activity in the crude mitochondrial-rich (10,000 [times] g pellet) fraction was low and PG had no effect. PG inhibited DMN and 4-NPOH, indicators of IIE1-dependent activity, and the formation of APAP-glutathione conjugates and APAP-protein adducts in both heavy (15,000 [times] g pellet) and light (100,000 [times] g pellet) microsomes. PAD, a measure of IA2-dependent activity, was not inhibited. These data demonstrate that PG selectively inhibits IIE1 activity, including the bioactivation of APAP, and implicates this as the mechanism for PG-mediated protection of APAP hepatotoxicity in mice. 27 refs., 1 fig., 1 tab.

• OSTI ID: 7062445
• Journal Information: Life Sciences; (United States), Vol. 52:2; ISSN 0024-3205
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
GLYCOLS
BIOLOGICAL EFFECTS
TOXICITY
CYTOCHROMES
EXPERIMENTAL DATA
LIVER
METABOLISM
PROPYLENE
ALCOHOLS
ALKENES
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GLANDS
HYDROCARBONS
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INFORMATION
NUMERICAL DATA
ORGANIC COMPOUNDS
ORGANS
PIGMENTS
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560300* - Chemicals Metabolism & Toxicology