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 FeCl(3) (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+4-HDA). 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 Fe(3+) 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 Fe(3+) was prevented by IPA only at the highest concentration (10 mM). It is concluded that Fe(3+)-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.

Iron affects the structure of cell membrane molecular models

“…The cell membrane is a selective barrier that protects the cell interior and its structure and functions are susceptible to alterations as a consequence of interaction with metals. Although the interaction of iron ions with cell membranes has been insufficiently studied (Ohba et al, 1994;Karbownik et al, 2001;Brunet et al, 1999), it has been reported that high concentrations of iron ions change neuronal membrane fluidity (Ohba et al, 1994).…”

Commensal microbiota is hepatoprotective and prevents liver fibrosis in mice

“…6 D ), confirming previously published results reported by us (17). IPA is a deamination product of dietary tryptophan, and it is a powerful antioxidant (40). Production of IPA is completely dependent on the presence of the gut microflora in particular Clostridium sporogenes (17).…”

“…6 E ). IPA protects primary neurons and hepatocytes from oxidative stress‐induced cell death (40, 41). As we observed increased hepatic oxidative stress in GF compared with conventional mice following TAA treatment (Fig.…”

Protective effects of melatonin in reducing oxidative stress and in preserving the fluidity of biological membranes: a review

“…Melatonin is the major indoleamine synthesized from tryptophan in organisms and is an important molecule that provides cellular protection and antioxidant activity. Several structurally related indoles, including 5‐hydroxytryptophan , 5‐methoxytryptophol , N‐acetylserotonin and indole‐3‐propionic acid , as well as pinoline, a ß‐carboline formed by condensation between indoleamines and aldehydes, may also act as powerful radical scavengers while stabilizing membranes .…”