Rousseau Ivan, Galleano Monica, Puntarulo Susana
Physical Chemistry-PRALIB, School of Pharmacy and Biochemistry, Buenos Aires, Argentina.
Toxicol Pathol. 2011 Dec;39(7):1075-83. doi: 10.1177/0192623311425057. Epub 2011 Oct 17.
The hypothesis of this study was that alterations in Fe distribution triggered by lipopolysaccharide (LPS) administration were affected in vivo by Fe overload. Lipopolysaccharide treatment by itself significantly decreased Fe content in serum and increased the blood NO-hemoglobin (NO-Hb) EPR signal and nitrotyrosine protein content in liver, as compared to values in control animals. Fe overload (produced by Fe-dextran ip administration) caused an increase, as compared to values in control animals, in Fe content in serum, and a significant enhancement in ferritin (Ft) content, Fe content in Ft, the labile Fe pool (LIP), and the protein carbonyl content in the liver. The simultaneous administration of LPS and Fe-dextran lead to a significant increase in the Fe content in serum, blood NO-Hb EPR signal, the content of Fe, Fe in Ft, LIP, protein carbonyl, and nitrotyrosine protein in liver, as compared to values in control animals. The data reported here indicate that the protective strategy against endotoxemia of sequestering serum Fe content is not fully operative under Fe overload conditions. However, the oxidative condition of the liver does not seem to be being affected, since endogenous mechanisms were able to regulate the amount of catalytically active Fe to the same levels observed after Fe-dextran administration, even in the presence of LPS, over the initial six-hour period.
本研究的假设是，铁过载在体内影响了由脂多糖（LPS）给药引发的铁分布改变。与对照动物的值相比，单独的脂多糖处理显著降低了血清中的铁含量，并增加了肝脏中的血液一氧化氮血红蛋白（NO-Hb）电子顺磁共振信号和硝基酪氨酸蛋白含量。与对照动物的值相比，铁过载（通过腹腔注射右旋糖酐铁产生）导致血清中铁含量增加，肝脏中铁蛋白（Ft）含量、Ft中的铁含量、不稳定铁池（LIP）和蛋白羰基含量显著升高。与对照动物的值相比，同时给予LPS和右旋糖酐铁导致血清中铁含量、血液NO-Hb电子顺磁共振信号、肝脏中铁、Ft中的铁、LIP、蛋白羰基和硝基酪氨酸蛋白含量显著增加。此处报告的数据表明，在铁过载条件下，隔离血清铁含量以对抗内毒素血症的保护策略并未完全起作用。然而，肝脏的氧化状态似乎未受影响，因为即使在存在LPS的情况下，内源性机制在最初的六小时内能够将具有催化活性的铁量调节至腹腔注射右旋糖酐铁后观察到的相同水平。
