Iwan Paulina, Stepniak Jan, Karbownik-Lewinska Malgorzata
Department of Oncological Endocrinology, Medical University of Lodz, 7/9 Zeligowski St., 90-752 Lodz, Poland.
Polish Mother's Memorial Hospital-Research Institute, 281/289 Rzgowska St., 93-338 Lodz, Poland.
Toxics. 2021 Apr 21;9(5):89. doi: 10.3390/toxics9050089.
Iodine deficiency is the main environmental factor leading to thyroid cancer. At the same time iodine excess may also contribute to thyroid cancer. Potassium iodate (KIO), which is broadly used in salt iodization program, may increase oxidative damage to membrane lipids (lipid peroxidation, LPO) under experimental conditions, with the strongest damaging effect at KIO concentration of ~10 mM (corresponding to physiological iodine concentration in the thyroid). Melatonin and indole-3-propionic acid (IPA) are effective antioxidative indoles, each of which protects against KIO-induced LPO in the thyroid. The study aims to check if melatonin used together with IPA (in their highest achievable in vitro concentrations) reveals stronger protective effects against KIO-induced LPO in porcine thyroid homogenates than each of these antioxidants used separately. Homogenates were incubated in the presence of KIO (200; 100; 50; 25; 20; 15; 10; 7.5; 5.0; 2.5; 1.25; 0.0 mM) without/with melatonin (5 mM) or without/with IPA (10 mM) or without/with melatonin + IPA, and then, to further clarify the narrow range of KIO concentrations, against which melatonin + IPA reveal cumulative protective effects, the following KIO concentrations were used: 20; 18.75; 17.5; 16.25; 15; 13.75; 12.5; 11.25; 10; 8.75; 7.5; 0.0 mM. Malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA) concentration (LPO index) was measured spectrophotometrically. Protective effects of melatonin + IPA were stronger than those revealed by each antioxidant used separately, but only when LPO was induced by KIO in concentrations from 18.75 mM to 8.75 mM, corresponding to physiological iodine concentration in the thyroid. In conclusion, melatonin and indole-3-propionic acid exert cumulative protective effects against oxidative damage caused by KIO, when this prooxidant is used in concentrations close to physiological iodine concentrations in the thyroid. Therefore, the simultaneous administration of these two indoles should be considered to prevent more effectively oxidative damage (and thereby thyroid cancer formation) caused by iodine compounds applied in iodine prophylaxis.
碘缺乏是导致甲状腺癌的主要环境因素。同时,碘过量也可能促使甲状腺癌的发生。广泛用于食盐碘化计划的碘酸钾(KIO)在实验条件下可能会增加对膜脂质的氧化损伤(脂质过氧化,LPO),在KIO浓度约为10 mM(相当于甲状腺中的生理碘浓度)时损伤作用最强。褪黑素和吲哚 - 3 - 丙酸(IPA)是有效的抗氧化吲哚,它们各自都能防止KIO诱导的甲状腺LPO。该研究旨在检验褪黑素与IPA一起使用(在它们可达到的最高体外浓度下)对猪甲状腺匀浆中KIO诱导的LPO的保护作用是否比单独使用这两种抗氧化剂更强。匀浆在有KIO(200;100;50;25;20;15;10;7.5;5.0;2.5;1.25;0.0 mM)且无/有褪黑素(5 mM)或无/有IPA(10 mM)或无/有褪黑素 + IPA的情况下孵育,然后,为了进一步明确褪黑素 + IPA显示出累积保护作用的KIO浓度的狭窄范围,使用了以下KIO浓度:20;18.75;17.5;16.25;15;13.75;12.5;11.25;10;8.75;7.5;0.0 mM。通过分光光度法测量丙二醛 + 4 - 羟基烯醛(MDA + 4 - HDA)浓度(LPO指标)。褪黑素 + IPA的保护作用比单独使用每种抗氧化剂更强,但仅当LPO由浓度为18.75 mM至8.75 mM的KIO诱导时才如此,这一浓度范围相当于甲状腺中的生理碘浓度。总之,当这种促氧化剂以接近甲状腺生理碘浓度的浓度使用时,褪黑素和吲哚 - 3 - 丙酸对KIO引起的氧化损伤发挥累积保护作用。因此,应考虑同时给予这两种吲哚,以更有效地预防碘预防中使用的碘化合物引起的氧化损伤(从而预防甲状腺癌形成)。