The contribution of the major metabolite 4'-O-methylmonoHER to the antioxidant activity of the flavonoid monoHER

K.J. Lemmens, P.M. Herst, B.A. Housmans, M. Moalin, W.J. van der Vijgh, A. Bast, G.R. Haenen

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The antioxidant flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER) effectively protects against doxorubicin-induced cardiotoxicity in mice. Doxorubicin is a very effective anticancer drug. The clinical use of doxorubicin is limited by severe cardiotoxicity. Free radicals, i.e., hydroxyl and superoxide radicals play a crucial role in this toxicity. In this study the involvement of the major metabolite of monoHER, 4'-O-methylmonoHER (methylmonoHER) in the protective effect of monoHER is studied. MethylmonoHER displayed antioxidant activity i.e., TEAC, hydroxyl and superoxide radical scavenging activity; nevertheless monoHER appeared to be superior compared to methylmonoHER. As a result of scavenging, flavonoids are oxidized and display reactivity towards thiols. Oxidized methylmonoHER, is far less thiol reactive towards creatine kinase than monoHER, which indicates that methylmonoHER is less toxic towards thiol containing enzymes. The thiol-reactivity of oxidized methylmonoHER was also negligible towards KEAP1 compared to monoHER. These results indicate that methylmonoHER hardly protects against radical damage via scavenging or via activating the NRF2 defense system. Also in HUVECs, methylmonoHER provided far less protection against oxidative stress (EC50>100muM) than monoHER which was a very potent protector (EC50=80nM). The results indicate that the contribution of methylmonoHER to the protection against doxorubicin-induced cardiotoxicity by monoHER is relatively low.
Original languageEnglish
Pages (from-to)146-152
Number of pages7
JournalChemico-Biological Interactions
Volume239
DOIs
Publication statusPublished - 5 Sep 2015

Keywords

  • MonoHER
  • MethylmonoHER
  • 4'-O-methylmonoHER
  • Doxorubicin
  • Antioxidant activity
  • DOXORUBICIN-INDUCED CARDIOTOXICITY
  • ENDOTHELIAL-CELLS
  • OXIDATIVE STRESS
  • PREVENTION
  • QUERCETIN
  • MECHANISM
  • PROTECT
  • DAMAGE

Cite this

Lemmens, K.J. ; Herst, P.M. ; Housmans, B.A. ; Moalin, M. ; van der Vijgh, W.J. ; Bast, A. ; Haenen, G.R. / The contribution of the major metabolite 4'-O-methylmonoHER to the antioxidant activity of the flavonoid monoHER. In: Chemico-Biological Interactions. 2015 ; Vol. 239. pp. 146-152.
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abstract = "The antioxidant flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER) effectively protects against doxorubicin-induced cardiotoxicity in mice. Doxorubicin is a very effective anticancer drug. The clinical use of doxorubicin is limited by severe cardiotoxicity. Free radicals, i.e., hydroxyl and superoxide radicals play a crucial role in this toxicity. In this study the involvement of the major metabolite of monoHER, 4'-O-methylmonoHER (methylmonoHER) in the protective effect of monoHER is studied. MethylmonoHER displayed antioxidant activity i.e., TEAC, hydroxyl and superoxide radical scavenging activity; nevertheless monoHER appeared to be superior compared to methylmonoHER. As a result of scavenging, flavonoids are oxidized and display reactivity towards thiols. Oxidized methylmonoHER, is far less thiol reactive towards creatine kinase than monoHER, which indicates that methylmonoHER is less toxic towards thiol containing enzymes. The thiol-reactivity of oxidized methylmonoHER was also negligible towards KEAP1 compared to monoHER. These results indicate that methylmonoHER hardly protects against radical damage via scavenging or via activating the NRF2 defense system. Also in HUVECs, methylmonoHER provided far less protection against oxidative stress (EC50>100muM) than monoHER which was a very potent protector (EC50=80nM). The results indicate that the contribution of methylmonoHER to the protection against doxorubicin-induced cardiotoxicity by monoHER is relatively low.",
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author = "K.J. Lemmens and P.M. Herst and B.A. Housmans and M. Moalin and {van der Vijgh}, W.J. and A. Bast and G.R. Haenen",
year = "2015",
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The contribution of the major metabolite 4'-O-methylmonoHER to the antioxidant activity of the flavonoid monoHER. / Lemmens, K.J.; Herst, P.M.; Housmans, B.A.; Moalin, M.; van der Vijgh, W.J.; Bast, A.; Haenen, G.R.

In: Chemico-Biological Interactions, Vol. 239, 05.09.2015, p. 146-152.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The contribution of the major metabolite 4'-O-methylmonoHER to the antioxidant activity of the flavonoid monoHER

AU - Lemmens, K.J.

AU - Herst, P.M.

AU - Housmans, B.A.

AU - Moalin, M.

AU - van der Vijgh, W.J.

AU - Bast, A.

AU - Haenen, G.R.

PY - 2015/9/5

Y1 - 2015/9/5

N2 - The antioxidant flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER) effectively protects against doxorubicin-induced cardiotoxicity in mice. Doxorubicin is a very effective anticancer drug. The clinical use of doxorubicin is limited by severe cardiotoxicity. Free radicals, i.e., hydroxyl and superoxide radicals play a crucial role in this toxicity. In this study the involvement of the major metabolite of monoHER, 4'-O-methylmonoHER (methylmonoHER) in the protective effect of monoHER is studied. MethylmonoHER displayed antioxidant activity i.e., TEAC, hydroxyl and superoxide radical scavenging activity; nevertheless monoHER appeared to be superior compared to methylmonoHER. As a result of scavenging, flavonoids are oxidized and display reactivity towards thiols. Oxidized methylmonoHER, is far less thiol reactive towards creatine kinase than monoHER, which indicates that methylmonoHER is less toxic towards thiol containing enzymes. The thiol-reactivity of oxidized methylmonoHER was also negligible towards KEAP1 compared to monoHER. These results indicate that methylmonoHER hardly protects against radical damage via scavenging or via activating the NRF2 defense system. Also in HUVECs, methylmonoHER provided far less protection against oxidative stress (EC50>100muM) than monoHER which was a very potent protector (EC50=80nM). The results indicate that the contribution of methylmonoHER to the protection against doxorubicin-induced cardiotoxicity by monoHER is relatively low.

AB - The antioxidant flavonoid 7-mono-O-(beta-hydroxyethyl)-rutoside (monoHER) effectively protects against doxorubicin-induced cardiotoxicity in mice. Doxorubicin is a very effective anticancer drug. The clinical use of doxorubicin is limited by severe cardiotoxicity. Free radicals, i.e., hydroxyl and superoxide radicals play a crucial role in this toxicity. In this study the involvement of the major metabolite of monoHER, 4'-O-methylmonoHER (methylmonoHER) in the protective effect of monoHER is studied. MethylmonoHER displayed antioxidant activity i.e., TEAC, hydroxyl and superoxide radical scavenging activity; nevertheless monoHER appeared to be superior compared to methylmonoHER. As a result of scavenging, flavonoids are oxidized and display reactivity towards thiols. Oxidized methylmonoHER, is far less thiol reactive towards creatine kinase than monoHER, which indicates that methylmonoHER is less toxic towards thiol containing enzymes. The thiol-reactivity of oxidized methylmonoHER was also negligible towards KEAP1 compared to monoHER. These results indicate that methylmonoHER hardly protects against radical damage via scavenging or via activating the NRF2 defense system. Also in HUVECs, methylmonoHER provided far less protection against oxidative stress (EC50>100muM) than monoHER which was a very potent protector (EC50=80nM). The results indicate that the contribution of methylmonoHER to the protection against doxorubicin-induced cardiotoxicity by monoHER is relatively low.

KW - MonoHER

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KW - 4'-O-methylmonoHER

KW - Doxorubicin

KW - Antioxidant activity

KW - DOXORUBICIN-INDUCED CARDIOTOXICITY

KW - ENDOTHELIAL-CELLS

KW - OXIDATIVE STRESS

KW - PREVENTION

KW - QUERCETIN

KW - MECHANISM

KW - PROTECT

KW - DAMAGE

U2 - 10.1016/j.cbi.2015.07.004

DO - 10.1016/j.cbi.2015.07.004

M3 - Article

VL - 239

SP - 146

EP - 152

JO - Chemico-Biological Interactions

JF - Chemico-Biological Interactions

SN - 0009-2797

ER -