Oxygen and redox-active drugs

Shared toxicity sites

Olen R. Brown, Richard Seither

Research output: Contribution to journalArticle

Abstract

Oxygen and Redox-Active Drugs: Shared Toxicity Sites. Brown, O.R. and Seither, R.L. (19S3).Fundam. Appl. Toxicol. 3:209-214. Paraquat and nitrofurantoin can accept single electrons and, under appropriate conditions in tissues and cells, can pass these electrons to oxygen, thus participating in redox cycling. Similarities in the response of the target organ (the lung) and in subsequent pathology have also been observed among animals poisoned by oxygen and by these chemicals. We report evidence primarily obtained from Escherichia coli for common biochemical sites of toxicity for these agents. Common sites for oxygen and paraquat involve biosynthesis of specific amino acids, induction of genetic stringency via unloaded tRNAs resulting from amino acid deficiencies, decreased thiamin content, and impaired biosynthesis of pyridine nucleotide coenzyme biosynthesis for paraquat and oxygen. Inhibition of specific amino acid biosynthesis and induction of stringency also have been observed for nitrofurantoin. RNA and DNA biosynthesis are also impaired by oxygen; this has not been examined for paraquat or nitrofurantoin. There is a biochemical basis and preliminary data to support inhibition of NAD biosynthesis as a component of mammalian toxicity for these agents. Niacin may act to circumvent the consequences of the biochemical lesion at quinolinate phosphori-bosyl transferase in NAD biosynthesis.

Original languageEnglish (US)
Pages (from-to)209-214
Number of pages6
JournalToxicological Sciences
Volume3
Issue number4
DOIs
StatePublished - Jul 1983
Externally publishedYes

Fingerprint

Biosynthesis
Drug-Related Side Effects and Adverse Reactions
Paraquat
Oxidation-Reduction
Toxicity
Reactive Oxygen Species
Nitrofurantoin
Oxygen
Pharmaceutical Preparations
Amino Acid-Specific Transfer RNA
Electrons
Thiamine Deficiency
Quinolinic Acid
NAD
Amino Acids
Niacin
Coenzymes
Transcriptional Activation
Thiamine
Nucleotides

ASJC Scopus subject areas

  • Molecular Biology
  • Embryology
  • Cell Biology
  • Genetics
  • Developmental Biology
  • Toxicology

Cite this

Oxygen and redox-active drugs : Shared toxicity sites. / Brown, Olen R.; Seither, Richard.

In: Toxicological Sciences, Vol. 3, No. 4, 07.1983, p. 209-214.

Research output: Contribution to journalArticle

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