Joint toxic effects of the type-2 alkene electrophiles

Lihai Zhang, Brian C. Geohagen, Terrence Gavin, Richard M. LoPachin

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Human populations are exposed to complex environmental mixtures of acrolein, methylvinyl ketone (MVK) and other type-2 alkenes. Many members of this chemical class are electrophiles that possess a common molecular mechanism of toxicity; i.e., protein inactivation via formation of stable cysteine adducts. Therefore, acute or chronic exposure to type-2 alkene mixtures could represent a health risk due to additive or synergistic interactions among component chemicals. Despite this risk, there is little experimental information regarding the joint effects of type-2 alkenes. In the present study we used sum of toxic units (TUsum = ?TUi) to assess the relative toxicity of different type-2 alkene mixtures. These studies involved well characterized environmental type-2 alkene toxicants and included amide (acrylamide; ACR), ketone (methyl vinyl ketone; MVK), aldehyde (2-ethylacrolein; EA) and ester (methyl acrylate; MA) derivatives. In chemico analyses revealed that both binary and ternary mixtures could deplete thiol groups according to an additive joint effect at equitoxic and non-equitoxic ratios; i.e., TUsum = 1.0 ± 0.20. In contrast, analyses of joint effects in SNB19 cell cultures indicated that different permutations of type-2 alkene mixtures produced mostly synergistic joint effects with respect to cell lethality; i.e., TUsum <0.80. A mixture of ACR and MA was shown to produce joint toxicity in a rat model. This mixture accelerated the onset and development of neurotoxicity relative to the effects of the individual toxicants. Synergistic effects in biological models might occur when different cellular proteomes are targeted, whereas additive effects develop when the mixtures encompasses a similar proteome.

Original languageEnglish (US)
Pages (from-to)198-206
Number of pages9
JournalChemico-Biological Interactions
Volume254
DOIs
StatePublished - Jul 25 2016

Fingerprint

Poisons
Alkenes
Proteome
Toxicity
Acrolein
Biological Models
Acrylamide
Ketones
Complex Mixtures
Sulfhydryl Compounds
Aldehydes
Cysteine
Health risks
Esters
Cell Culture Techniques
Joints
Cell culture
Rats
Health
Derivatives

Keywords

  • Acrylamide
  • Additive
  • Concentration addition
  • Environmental toxicology
  • Synergistic
  • Toxicant mixture

ASJC Scopus subject areas

  • Toxicology

Cite this

Joint toxic effects of the type-2 alkene electrophiles. / Zhang, Lihai; Geohagen, Brian C.; Gavin, Terrence; LoPachin, Richard M.

In: Chemico-Biological Interactions, Vol. 254, 25.07.2016, p. 198-206.

Research output: Contribution to journalArticle

Zhang, Lihai ; Geohagen, Brian C. ; Gavin, Terrence ; LoPachin, Richard M. / Joint toxic effects of the type-2 alkene electrophiles. In: Chemico-Biological Interactions. 2016 ; Vol. 254. pp. 198-206.
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