Bile and bile salts potentiate superoxide anion release from activated, rat peritoneal neutrophils

Lawrence J. Dahm, James Hewett, Robert A. Roth

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Certain bile salts cause hepatotoxicity as well as injury to extrahepatic organs when administered to animals. Activated neutrophils (PMNs) may cause tissue injury by releasing reactive oxygen species and other products. Since PMNs may come in contact with biliary components, such as bile salts, following chemical insult to the liver or during cholestasis, we examined the capacity of bile and bile salts to stimulate superoxide anion (O-2) release from rat peritoneal PMNs in vitro. Neither bile nor bile salts, with the exception of lithocholate, could by themselves stimulate O-2 release from PMNs. Lithocholate (32 μM) caused small but statistically significant release of O-2 from PMNs. When PMNs were primed with a barely suprathreshold concentration of 12-O-tetradecanoyl-phorbol-13-acetate (PMA), a classic stimulus for PMNs, the addition of bile and certain bile salts markedly enhanced O-2 release from PMNs. The monohydroxy bile salt, lithocholate, had the greatest stimulatory activity toward PMA-primed PMNs, causing approximately an eightfold increase in O-2 release. The enhancing effect of lithocholate was maximal between 10 and 32 μM, and it also occurred with PMNs isolated from rat blood. Dihydroxy bile salts, deoxycholate and chenodeoxycholate (100 μM), caused more modest enhancement of O-2 release (two- to threefold) from primed PMNs. Cholate, a trihydroxy bile salt, was not active at these concentrations. Conjugation of either lithocholate or chenodeoxycholate with either glycine or taurine markedly reduced the ability of the bile salt to enhance O-2 release from primed PMNs. Structural alterations on the hydrophilic side chain or within the planar, hydrophobic portion of the bile salt molecule reduced the capacity to enhance O-2 release from PMA-primed PMNs. These results indicate that bile salts can potentiate the respiratory burst in PMNs and suggest a role for this interaction in toxicoses or disease states characterized by elevated serum bile salts.

Original languageEnglish (US)
Pages (from-to)82-92
Number of pages11
JournalToxicology and Applied Pharmacology
Volume95
Issue number1
DOIs
StatePublished - 1988
Externally publishedYes

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ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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