Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activation

Jong Hee Sohn, Kyu Lee Han, Jeong Hwan Kim, Yaya Rukayadi, Jae-Kwan Hwang

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Cisplatin is one of the most effective antineoplastic drugs, but it has undesirable side effects such as hepatotoxicity at high doses. This study investigated the protective effect of macelignan, isolated from Myristica fragrans HOUTT. (nutmeg), against cisplatin-induced hepatotoxicity and the possible mechanisms involved in these effects in mice. Pretreatment with macelignan for 4 d significantly prevented the increased serum enzymatic activities of alanine and aspartate aminotransferase in a dose-dependent manner. The results also showed that the protective effects of macelignan on cisplatin-induced hepatotoxicity may be associated with the mitogen activated protein kinase (MAPK) signaling pathway. Cisplatin-induced phosphorylation of c-Jun N-terminal kinase1/2 (JNK1/2) and extracellular signal-regulated kinase1/2 (ERK1/2) was abrogated by pretreatment with macelignan, however, that of p38 was not significantly affected. It was also found that macelignan attenuated the expression of phosphorylated c-Jun in cisplatin-treated mice. Accordingly, it is suggested that the hepatoprotective effects of macelignan could be related to activation of the MAPK signaling pathway, especially JNK and c-Jun, its substrate. The present findings suggest that co-treatment of cisplatin with macelignan may provide more advantage than cisplatin treatment alone in cancer therapy.

Original languageEnglish
Pages (from-to)273-277
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume31
Issue number2
DOIs
Publication statusPublished - 2008 Feb 1

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Cisplatin
Myristica fragrans
Mitogen-Activated Protein Kinases
MAP Kinase Signaling System
Aspartate Aminotransferases
macelignan
Alanine Transaminase
Antineoplastic Agents
Phosphorylation
Serum
Neoplasms

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Sohn, Jong Hee ; Han, Kyu Lee ; Kim, Jeong Hwan ; Rukayadi, Yaya ; Hwang, Jae-Kwan. / Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activation. In: Biological and Pharmaceutical Bulletin. 2008 ; Vol. 31, No. 2. pp. 273-277.
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Protective effects of macelignan on cisplatin-induced hepatotoxicity is associated with JNK activation. / Sohn, Jong Hee; Han, Kyu Lee; Kim, Jeong Hwan; Rukayadi, Yaya; Hwang, Jae-Kwan.

In: Biological and Pharmaceutical Bulletin, Vol. 31, No. 2, 01.02.2008, p. 273-277.

Research output: Contribution to journalArticle

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