Boisier X, Schön M, Sepúlveda A, Basualdo A, Cornejo P, Bosco C, Carrión Y, Galleano M, Tapia G, Puntarulo S, Fernández V, Videla L A
Programas de Farmacología Molecular y Clínica, Facultad de Medicina, Universidad de Chile, Santiago.
Redox Rep. 1999;4(5):243-50. doi: 10.1179/135100099101534963.
Liver oxidative stress, Kupffer cell functioning, and cell injury were studied in control rats and in animals subjected to L-3,3',5-tri-iodothyronine (T3) and/or acute iron overload. Thyroid calorigenesis with increased rates of hepatic O2 uptake was not altered by iron treatment, whereas iron enhanced serum and liver iron levels independently of T3. Liver thiobarbituric acid reactants formation increased by 5.8-, 5.7-, or 11.0-fold by T3, iron, or their combined treatment, respectively. Iron enhanced the content of protein carbonyls independently of T3 administration, whereas glutathione levels decreased in T3- and iron-treated rats (54%) and in T3Fe-treated animals (71%). Colloidal carbon infusion into perfused livers elicited a 109% and 68% increase in O2 uptake in T3 and iron-treated rats over controls. This parameter was decreased (78%) by the joint T3Fe administration and abolished by gadolinium chloride (GdCl3) pretreatment in all experimental groups. Hyperthyroidism and iron overload did not modify the sinusoidal efflux of lactate dehydrogenase, whereas T3Fe-treated rats exhibited a 35-fold increase over control values, with a 54% reduction by GdCl3 pretreatment. Histological studies showed a slight increase in the number or size of Kupffer cells in hyperthyroid rats or in iron overloaded animals, respectively. Kupffer cell hypertrophy and hyperplasia with presence of inflammatory cells and increased hepatic myeloperoxidase activity were found in T3Fe-treated rats. It is concluded that hyperthyroidism increases the susceptibility of the liver to the toxic effects of iron, which seems to be related to the development of a severe oxidative stress status in the tissue, thus contributing to the concomitant liver injury and impairment of Kupffer cell phagocytosis and particle-induced respiratory burst activity.
在对照大鼠以及接受L-3,3',5-三碘甲状腺原氨酸（T3）和/或急性铁过载的动物中，研究了肝脏氧化应激、库普弗细胞功能和细胞损伤。甲状腺产热以及肝脏氧气摄取率的增加不受铁处理的影响，而铁独立于T3增加了血清和肝脏铁水平。T3、铁或它们的联合处理分别使肝脏硫代巴比妥酸反应物的形成增加了5.8倍、5.7倍或11.0倍。铁独立于T3给药增加了蛋白质羰基的含量，而在T3和铁处理的大鼠（54%）以及T3Fe处理的动物（71%）中谷胱甘肽水平降低。向灌注肝脏中注入胶体碳，在T3和铁处理的大鼠中，氧气摄取量比对照组分别增加了109%和68%。在所有实验组中，联合给予T3Fe会使该参数降低（78%），而用氯化钆（GdCl3）预处理可消除该影响。甲状腺功能亢进和铁过载并未改变乳酸脱氢酶的窦状隙外流，而T3Fe处理的大鼠比对照值增加了35倍，用GdCl3预处理可使其降低54%。组织学研究表明，甲状腺功能亢进大鼠或铁过载动物中库普弗细胞的数量或大小分别略有增加。在T3Fe处理的大鼠中发现库普弗细胞肥大和增生，伴有炎症细胞的存在以及肝脏髓过氧化物酶活性增加。结论是，甲状腺功能亢进增加了肝脏对铁毒性作用的易感性，这似乎与组织中严重氧化应激状态的发展有关，从而导致伴随的肝脏损伤以及库普弗细胞吞噬作用和颗粒诱导的呼吸爆发活性受损。
