The temporal relationship between hepatic gsh loss, heme oxygenase induction, and cytochrome p450 loss following intraperitoneal aluminum administration to mice

Barbara Fulton, Elizabeth H. Jeffery

Research output: Contribution to journalArticlepeer-review

Abstract

The time- and dose-dependent accumulation of aluminum (Al) in liver and its effect on several hepatic systems were investigated in Swiss-Webster mice given intraperitoneal (ip) Al lactate. A single dose of 50, 75, or 100 mg Al/kg produced significant depletion of hepatic glutathione (GSH) and cytochrome P450 (P450) and an increase in heme oxygenase (HO) activity when measured at 6 hr. However, no increase in hepatic malondialdehyde (MDA) was seen at this time. Using a dose of 100 mg Al/kg, Al rapidly accumulated in liver (0.29±0.03 vs 0.12±0.04 μg Al/mg protein at 6 hr). Hepatic GSH was significantly depleted at 2, 4, and 6 hr postdosing, HO activity was significantly increased at 6, 12, 24, 48, and 96 hr postdosing, hepatic cytochrome P450 was decreased at 12, 18, 24, and 48 hr postdosing, while hepatic MDA was not significantly elevated until 24 hr postdosing. Twenty-four hours following three daily doses of 50 mg Al/kg, HO activity was increased, P450 levels were depleted, and hepatic Al content was significantly increased, although hepatic MDA was unaffected. We conclude that parenteral Al produces a course of hepatic damage that begins with GSH depletion and proceeds through a sustained increase in HO activity, with cytochrome P450 loss being an early event and production of hepatic MDA being a late event.

Original languageEnglish (US)
Pages (from-to)291-297
Number of pages7
JournalToxicology and Applied Pharmacology
Volume127
Issue number2
DOIs
StatePublished - Mar 3 1994

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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