Involvement of oxidative stress in paraquat-induced metallothionein synthesis under glutathione depletion

Ippei Nakagawa, Mieko Suzuki, Nobumasa Imura, Akira Naganuma

Research output: Contribution to journalArticlepeer-review

35 Citations (Scopus)

Abstract

The inhibition of glutathione (GSH) synthesis by L-buthionine-SR- sulfoximine (BSO) causes aggravation of hepatotoxicity of paraquat (PQ), an oxidative-stress inducing substance, in mice. On the other hand, synthesis of metallothionein (MT), a cysteine-rich protein having radical scavenging activity, is induced by PQ, and the induction by PQ is significantly enhanced by pretreatment of mice with BSO. The purpose of present study is to examine whether generation of reactive oxygens is involved in the induction of MT synthesis by PQ under inhibition of GSH synthesis. Administration of PQ to BSO-pretreated mice increased hepatic lipid peroxidation and frequency of DNA single strand breakage followed by manifestation of the liver injury and induction of MT synthesis. Both vitamin E and deferoxamine prevented MT induction as well as lipid peroxidation in the liver of mice caused by administration of BSO and PQ. In cultured colon 26 cells, both cytotoxicity and the increase in MT mRNA level caused by PQ were significantly enhanced by pretreatment with BSO. Facilitation of PQ-induced reactive oxygen generation was also observed by BSO treatment. These results suggest that reactive oxygens generated by PQ under inhibition of GSH synthesis may stimulate MT synthesis. GSH depletion markedly increased reactive oxygen generation induced by PQ, probably due to the reduced cellular capability to remove the radical species produced.

Original languageEnglish
Pages (from-to)1390-1395
Number of pages6
JournalFree Radical Biology and Medicine
Volume24
Issue number9
DOIs
Publication statusPublished - 1998 Jun

Keywords

  • Free radicals
  • Glutathione
  • L-Buthionine-SR- sulfoximine
  • Metallothionein
  • Mouse
  • Paraquat
  • Reactive oxygens

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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