Melatonin and Indole-3-Propionic Acid Reduce Oxidative Damage to Membrane Lipids Induced by High Iron Concentrations in Porcine Skin

Abstract

Iron excess in tissues results in increased oxidative damage. Among different tissues, the skin can particularly be severely damaged by oxidative stress, as it is exposed not only to endogenous but also directly to exogenous pro-oxidants. The skin is especially vulnerable to harmful oxidative stress. Melatonin and indole-3-propionic acid (IPA), two indole substances, are efficient antioxidants. This study aims to evaluate the potential protective effects of melatonin and IPA against oxidative damage to membrane lipids (lipid peroxidation (LPO)), induced in porcine skin homogenates by the Fenton reaction (Fe2+ + H2O2 → Fe3+ + •OH + OH−) when iron is used in extremely high concentrations. Skin homogenates were incubated in the presence of FeSO4 (2400, 1200, 600, 300, 150 and 75 µM) + H2O2 (5 mM) with/without melatonin or IPA. LPO level (MDA + 4-HDA/mg protein) was measured spectrophotometrically. Melatonin, in its highest used concentration (5.0 mM), prevented FeSO4 (1200 mM)-induced LPO, whereas it was effective in concentrations as low as 2.5 mM against all lower iron concentrations. IPA was protective in concentrations as low as 2.5 mM independently of FeSO4 concentration. In conclusion, melatonin and IPA effectively protect against oxidative damage to membrane lipids induced by high concentrations of iron in porcine skin; therefore, both can be considered pharmacological agents in the case of disorders associated with excessive iron accumulation in the skin.

Biological Effects of Indole-3-Propionic Acid, a Gut Microbiota-Derived Metabolite, and Its Precursor Tryptophan in Mammals’ Health and Disease

“…IS, the liver metabolite of microbiota-derived indole, promotes the production of reactive oxygen species (ROS) [124] and induces expression of proinflammatory cytokines, including IL-1β [125], TNF-α [125] and MCP-1 [125][126][127]. Interestingly, IPA protects cells from ROS [25,128,129], oxidative damage and lipid peroxidation caused by potassium bromate [130][131][132], potassium iodate [24], iron (II) sulphate [133,134], iron (III) chloride [135], chromium (III) chloride [136], and 2,2 -Azino-bis(3-ethylbenzothiazoline-6sulfonic acid (ABTS) [137]. Additionally, IPA decreases the expression of proinflammatory cytokines, including TNF-α [22,27,121], IL-1β [23,27], IL-6 [27], IL-12 [22], IL-13 [22] and MCP-1 [22,82].…”

“…Melatonin has antioxidative action, and also increases clearance of amyloid β-protein in the mice model of Alzheimer's disease amyloidosis [157]. IPA shares protective biological effects against oxidative stress with melatonin [24,133] and decreases aggregation of amyloid β-protein in in vitro experiments [158]. The addition of IPA to media of the primary neurons and neuroblastoma cells exposed to amyloid β-protein significantly reduced toxicity and prevented cell death [159].…”

Effects of Dietary Indole-3-carboxaldehyde Supplementation on Growth Performance, Intestinal Epithelial Function, and Intestinal Microbial Composition in Weaned Piglets

“…found that indoleacrylic acid, but not indolepropionic acid, had an anti-oxidative and anti-inflammatory function in LPS-activated human peripheral blood mono-nuclear cells, which reduced IL-6 and IL-1β secretion, and activated the NRF2-ARE pathway ( 31 ). Indole-3-propionic acid protected cells from reactive oxygen species (ROS), oxidative damage, and lipid peroxidation ( 32 – 34 ). In the current study, dietary ICA supplementation in pigs did not change the antioxidant enzyme activities in serum, including SOD, GSH-Px, CAT, T-AOC, and MDA, suggesting ICA have no anti-oxidative effect in circulation.…”

Membrane Lipids in the Thyroid Comparing to Those in Non-Endocrine Tissues Are Less Sensitive to Pro-Oxidative Effects of Fenton Reaction Substrates

“…Until now, Fenton reaction substrates were used very commonly to experimentally induce oxidative damage to macromolecules in different tissues (e.g., ovary, thyroid, and skin) with very high Fe 2+ concentrations (Rynkowska et al, 2020(Rynkowska et al, , 2021, equal to these used in the present study.…”