Indole-3-propionic acid, a melatonin-related molecule, protects hepatic microsomal membranes from iron-induced oxidative damage

Relevance to cancer reduction

Magorzata Karbownik, Russel J Reiter, Joaquin J. Garcia, Javier Cabrera, Susanne Burkhardt, Carmen Osuna, Andrzej Lewiski

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Excessive free iron and the associated oxidative damage are commonly related to carcinogenesis. Among the antioxidants known to protect against iron-induced oxidative abuse and carcinogenesis, melatonin and other indole compounds recently have received considerable attention. Indole-3-propionic acid (IPA), a deamination product of tryptophan, with a structure similar to that of melatonin, is present in biological fluids and is an effective free radical scavenger. The aim of the study was to examine the effect of IPA on experimentally induced oxidative changes in rat hepatic microsomal membranes. Microsomes were preincubated in presence of IPA (10, 3, 2, 1, 0.3, 0.1, 0.01 or 0.001 mM) and, then, incubated with FeCl3 (0.2 mM), ADP (1.7 mM) and NADPH (0.2 mM) to induce oxidative damage. Alterations in membrane fluidity (the inverse of membrane rigidity) were estimated by fluorescence spectroscopy and lipid peroxidation by measuring concentrations of malondialdehyde+ 4-hydroxyalkenals (MDA+4HDA). IPA, when used in concentrations of 10, 3 or 2 mM, increased membrane fluidity, although at these concentrations it did not influence lipid peroxidation significantly. The decrease in membrane fluidity due to Fe3+ was completely prevented by preincubation in the presence of IPA at concentrations of 10, 3, 2 or 1 mM. The enhanced lipid peroxidation due to Fe3+ was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe3+induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA. However, IPA in high concentrations increase membrane fluidity. Besides melatonin, IPA may be used as a pharmacological agent to protect against iron-induced oxidative damage to membranes and, potentially, against carcinogenesis.

Original languageEnglish (US)
Pages (from-to)507-513
Number of pages7
JournalJournal of Cellular Biochemistry
Volume81
Issue number3
DOIs
StatePublished - 2001

Fingerprint

Melatonin
Iron
Membranes
Molecules
Liver
Membrane Fluidity
Fluidity
Neoplasms
Lipid Peroxidation
Lipids
Carcinogenesis
Rigidity
indole
propionic acid
Deamination
Free Radical Scavengers
Fluorescence Spectrometry
Fluorescence spectroscopy
Microsomes
Malondialdehyde

Keywords

  • Cancer
  • Indole-3-propionic acid
  • Iron
  • Lipid peroxidation
  • Membrane fluidity

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Indole-3-propionic acid, a melatonin-related molecule, protects hepatic microsomal membranes from iron-induced oxidative damage : Relevance to cancer reduction. / Karbownik, Magorzata; Reiter, Russel J; Garcia, Joaquin J.; Cabrera, Javier; Burkhardt, Susanne; Osuna, Carmen; Lewiski, Andrzej.

In: Journal of Cellular Biochemistry, Vol. 81, No. 3, 2001, p. 507-513.

Research output: Contribution to journalArticle

Karbownik, Magorzata ; Reiter, Russel J ; Garcia, Joaquin J. ; Cabrera, Javier ; Burkhardt, Susanne ; Osuna, Carmen ; Lewiski, Andrzej. / Indole-3-propionic acid, a melatonin-related molecule, protects hepatic microsomal membranes from iron-induced oxidative damage : Relevance to cancer reduction. In: Journal of Cellular Biochemistry. 2001 ; Vol. 81, No. 3. pp. 507-513.
@article{be9f0e1f26ed49a9b4d20a871ea9e39c,
title = "Indole-3-propionic acid, a melatonin-related molecule, protects hepatic microsomal membranes from iron-induced oxidative damage: Relevance to cancer reduction",
abstract = "Excessive free iron and the associated oxidative damage are commonly related to carcinogenesis. Among the antioxidants known to protect against iron-induced oxidative abuse and carcinogenesis, melatonin and other indole compounds recently have received considerable attention. Indole-3-propionic acid (IPA), a deamination product of tryptophan, with a structure similar to that of melatonin, is present in biological fluids and is an effective free radical scavenger. The aim of the study was to examine the effect of IPA on experimentally induced oxidative changes in rat hepatic microsomal membranes. Microsomes were preincubated in presence of IPA (10, 3, 2, 1, 0.3, 0.1, 0.01 or 0.001 mM) and, then, incubated with FeCl3 (0.2 mM), ADP (1.7 mM) and NADPH (0.2 mM) to induce oxidative damage. Alterations in membrane fluidity (the inverse of membrane rigidity) were estimated by fluorescence spectroscopy and lipid peroxidation by measuring concentrations of malondialdehyde+ 4-hydroxyalkenals (MDA+4HDA). IPA, when used in concentrations of 10, 3 or 2 mM, increased membrane fluidity, although at these concentrations it did not influence lipid peroxidation significantly. The decrease in membrane fluidity due to Fe3+ was completely prevented by preincubation in the presence of IPA at concentrations of 10, 3, 2 or 1 mM. The enhanced lipid peroxidation due to Fe3+ was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe3+induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA. However, IPA in high concentrations increase membrane fluidity. Besides melatonin, IPA may be used as a pharmacological agent to protect against iron-induced oxidative damage to membranes and, potentially, against carcinogenesis.",
keywords = "Cancer, Indole-3-propionic acid, Iron, Lipid peroxidation, Membrane fluidity",
author = "Magorzata Karbownik and Reiter, {Russel J} and Garcia, {Joaquin J.} and Javier Cabrera and Susanne Burkhardt and Carmen Osuna and Andrzej Lewiski",
year = "2001",
doi = "10.1002/1097-4644(20010601)81:3<507::AID-JCB1064>3.0.CO;2-M",
language = "English (US)",
volume = "81",
pages = "507--513",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - Indole-3-propionic acid, a melatonin-related molecule, protects hepatic microsomal membranes from iron-induced oxidative damage

T2 - Relevance to cancer reduction

AU - Karbownik, Magorzata

AU - Reiter, Russel J

AU - Garcia, Joaquin J.

AU - Cabrera, Javier

AU - Burkhardt, Susanne

AU - Osuna, Carmen

AU - Lewiski, Andrzej

PY - 2001

Y1 - 2001

N2 - Excessive free iron and the associated oxidative damage are commonly related to carcinogenesis. Among the antioxidants known to protect against iron-induced oxidative abuse and carcinogenesis, melatonin and other indole compounds recently have received considerable attention. Indole-3-propionic acid (IPA), a deamination product of tryptophan, with a structure similar to that of melatonin, is present in biological fluids and is an effective free radical scavenger. The aim of the study was to examine the effect of IPA on experimentally induced oxidative changes in rat hepatic microsomal membranes. Microsomes were preincubated in presence of IPA (10, 3, 2, 1, 0.3, 0.1, 0.01 or 0.001 mM) and, then, incubated with FeCl3 (0.2 mM), ADP (1.7 mM) and NADPH (0.2 mM) to induce oxidative damage. Alterations in membrane fluidity (the inverse of membrane rigidity) were estimated by fluorescence spectroscopy and lipid peroxidation by measuring concentrations of malondialdehyde+ 4-hydroxyalkenals (MDA+4HDA). IPA, when used in concentrations of 10, 3 or 2 mM, increased membrane fluidity, although at these concentrations it did not influence lipid peroxidation significantly. The decrease in membrane fluidity due to Fe3+ was completely prevented by preincubation in the presence of IPA at concentrations of 10, 3, 2 or 1 mM. The enhanced lipid peroxidation due to Fe3+ was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe3+induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA. However, IPA in high concentrations increase membrane fluidity. Besides melatonin, IPA may be used as a pharmacological agent to protect against iron-induced oxidative damage to membranes and, potentially, against carcinogenesis.

AB - Excessive free iron and the associated oxidative damage are commonly related to carcinogenesis. Among the antioxidants known to protect against iron-induced oxidative abuse and carcinogenesis, melatonin and other indole compounds recently have received considerable attention. Indole-3-propionic acid (IPA), a deamination product of tryptophan, with a structure similar to that of melatonin, is present in biological fluids and is an effective free radical scavenger. The aim of the study was to examine the effect of IPA on experimentally induced oxidative changes in rat hepatic microsomal membranes. Microsomes were preincubated in presence of IPA (10, 3, 2, 1, 0.3, 0.1, 0.01 or 0.001 mM) and, then, incubated with FeCl3 (0.2 mM), ADP (1.7 mM) and NADPH (0.2 mM) to induce oxidative damage. Alterations in membrane fluidity (the inverse of membrane rigidity) were estimated by fluorescence spectroscopy and lipid peroxidation by measuring concentrations of malondialdehyde+ 4-hydroxyalkenals (MDA+4HDA). IPA, when used in concentrations of 10, 3 or 2 mM, increased membrane fluidity, although at these concentrations it did not influence lipid peroxidation significantly. The decrease in membrane fluidity due to Fe3+ was completely prevented by preincubation in the presence of IPA at concentrations of 10, 3, 2 or 1 mM. The enhanced lipid peroxidation due to Fe3+ was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe3+induced rigidity and, to a lesser extent, lipid peroxidation in microsomal membranes may be reduced by IPA. However, IPA in high concentrations increase membrane fluidity. Besides melatonin, IPA may be used as a pharmacological agent to protect against iron-induced oxidative damage to membranes and, potentially, against carcinogenesis.

KW - Cancer

KW - Indole-3-propionic acid

KW - Iron

KW - Lipid peroxidation

KW - Membrane fluidity

UR - http://www.scopus.com/inward/record.url?scp=0035042609&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035042609&partnerID=8YFLogxK

U2 - 10.1002/1097-4644(20010601)81:3<507::AID-JCB1064>3.0.CO;2-M

DO - 10.1002/1097-4644(20010601)81:3<507::AID-JCB1064>3.0.CO;2-M

M3 - Article

VL - 81

SP - 507

EP - 513

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 3

ER -