Stępniak Jan, Rynkowska Aleksandra, Karbownik-Lewińska Małgorzata
Department of Oncological Endocrinology, Medical University of Lodz, Lodz, Poland.
Polish Mother's Memorial Hospital-Research Institute, Lodz, Poland.
Front Mol Biosci. 2022 Jun 3;9:901062. doi: 10.3389/fmolb.2022.901062. eCollection 2022.
Iron is an essential microelement for the proper functioning of many organs, among others it is required for thyroid hormone synthesis. However, its overload contributes to the increased formation of reactive oxygen species via Fenton chemistry (Fe+HO→Fe+OH + OH), and it is potentially toxic. Individual organs/tissues are affected differently by excess iron. The excessive absorption of iron with subsequent deposition in various organs is associated with diseases such as hemochromatosis. Such an iron deposition also occurs in the thyroid gland where it can disturb thyroid hormone synthesis. In turn, melatonin is an effective antioxidant, which protects against oxidative damage. This study aims to check if lipid peroxidation resulting from oxidative damage to membrane lipids, is caused by Fenton reaction substrates, and if protective effects of melatonin differ between the thyroid and various non-endocrine porcine tissues (liver, kidney, brain cortex, spleen, and small intestine). To mimic the conditions of iron overload, Fe was used in extremely high concentrations. Homogenates of individual tissues were incubated together with Fenton reaction substrates, i.e., FeSO (9.375, 18.75, 37.5, 75, 150, 300, 600, 1,200, 1,800, 2,100, 2,400, 3,000, 3,600, 4,200, and 4,800 µM)+HO (5 mM), either without or with melatonin (5 mM). The concentration of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA), as the LPO index, was evaluated by a spectrophotometrical method. Fenton reaction substrates increased concentrations of LPO products in all chosen tissues. However, in the thyroid, compared to non-endocrine tissues, the damaging effect was generally weaker, it was not observed for the two lowest concentrations of iron, and the LPO peak occurred with higher concentrations of iron. Melatonin reduced experimentally induced LPO in all examined tissues (without differences between them), and these protective effects did not depend on iron concentration. In conclusion, membrane lipids in the thyroid compared to those in non-endocrine tissues are less sensitive to pro-oxidative effects of Fenton reaction substrates, without differences regarding protective effects of melatonin.
铁是许多器官正常运作所必需的微量元素，甲状腺激素合成也需要铁。然而，铁过载会通过芬顿化学反应（Fe²⁺+H₂O₂→Fe³⁺+OH⁻+OH·）导致活性氧生成增加，具有潜在毒性。过量的铁对各个器官/组织的影响不同。铁的过度吸收以及随后在各个器官中的沉积与血色素沉着症等疾病有关。这种铁沉积也会发生在甲状腺中，进而干扰甲状腺激素的合成。而褪黑素是一种有效的抗氧化剂，可防止氧化损伤。本研究旨在检验膜脂质氧化损伤导致的脂质过氧化是否由芬顿反应底物引起，以及褪黑素在甲状腺和各种非内分泌猪组织（肝脏、肾脏、大脑皮层、脾脏和小肠）中的保护作用是否存在差异。为模拟铁过载情况，使用了极高浓度的铁。将各个组织的匀浆与芬顿反应底物，即硫酸亚铁（9.375、18.75、37.5、75、150、300、600、1200、1800、2100、2400、3000、3600、4200和4800 μM）+过氧化氢（5 mM）一起孵育，分别在不加或添加褪黑素（5 mM）的情况下进行。通过分光光度法评估丙二醛+4-羟基烯醛（MDA+4-HDA）的浓度，作为脂质过氧化指标。芬顿反应底物使所有选定组织中的脂质过氧化产物浓度增加。然而，在甲状腺中，与非内分泌组织相比，损伤作用通常较弱，在最低的两种铁浓度下未观察到损伤，脂质过氧化峰值出现在更高的铁浓度时。褪黑素降低了所有检测组织中实验诱导的脂质过氧化（各组织之间无差异），且这些保护作用不依赖于铁浓度。总之，与非内分泌组织相比，甲状腺中的膜脂质对芬顿反应底物的促氧化作用不太敏感，褪黑素的保护作用没有差异。
