| Summary: | 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 (Fe<sup>2+</sup> + H<sub>2</sub>O<sub>2</sub> → Fe<sup>3+</sup> + <sup>•</sup>OH + OH<sup>−</sup>) when iron is used in extremely high concentrations. Skin homogenates were incubated in the presence of FeSO<sub>4</sub> (2400, 1200, 600, 300, 150 and 75 µM) + H<sub>2</sub>O<sub>2</sub> (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 FeSO<sub>4</sub> (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 FeSO<sub>4</sub> 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.
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