Simoni J, Simoni G, Garcia E L, Prien S D, Tran R M, Feola M, Shires G T
Texas Tech University Health Sciences Center, Department of Surgery, Lubbock 79430, USA.
Artif Cells Blood Substit Immobil Biotechnol. 1995;23(4):469-86. doi: 10.3109/10731199509117963.
The toxicity of hemoglobin (Hb) solutions is related, at least in part, to the generation of oxygen free radicals with consequent induction of lipid peroxidation. The present study was designed to examine whether selenium (Se) may prevent the oxidative damage observed after Hb administration. Three groups of rats were compared; (I) the negative control group receiving autotransfusion; (II) the positive control group with replacement of 40% total blood volume (TBV) with modified bovine Hb solution; and (III) the experimental group which received dietary supplemented selenium (Na2SeO3) in daily doses of 5 micrograms.kg body wt-1 in drinking water, 4 days before and 3 days after administration of Hb solution in the same volume as in group II. Three days after Hb injection, all animals were sacrificed. Oxidative stress was determined by measuring conjugated dienes (CD) and thiobarbituric acid reactants (MDA) in homogenates of the perfused liver, heart, lungs, kidney, brain and plasma. Additionally, the 45k x g supernatants of the organs homogenates and plasma were assayed for the antioxidant enzymes activity: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and the intracellular level of reduced glutathione (GSH). Also, a measurement of nonprotein bound intracellular free iron (Fe) and tissue Se concentrations was performed. Simultaneously, injury dysfunction of vital organs was assessed by the measurement of plasma LDH, SGPT, creatinine, blood PaO2 and by histopathological studies. Results indicate that the exchange transfusion with Hb solution introduced significant increases in CD and MDA formation, particularly in the liver and heart tissues, and in plasma. While the values of the SOD and CAT in the liver and heart tissue were generally altered, the SOD/CAT ratio was also increased. After the Hb injection, activity of GSH-Px remained unchanged and was associated with significant depletion of GSH. The plasma levels of SGPT and LDH were increased, but the creatinine and PaO2 was similar to that of the control and corresponded with histopathological findings. The liver and heart intracellular free Fe was found to be higher than that of control. Treatment with Se was very effective in the prevention of oxidative damage introduced by Hb. Full protection from MDA formation was noted in liver tissue (p < 0.001). Also, plasma levels of MDA, SGPT and LDH were significantly decreased and appeared similar to that of the control group (I). Treatment with Se increased liver (p < 0.05) and plasma (p < 0.1) level of GSH-Px.(ABSTRACT TRUNCATED AT 400 WORDS)
血红蛋白（Hb）溶液的毒性至少部分与氧自由基的产生及随之引发的脂质过氧化有关。本研究旨在检验硒（Se）是否可预防输注Hb后观察到的氧化损伤。比较了三组大鼠：（I）接受自体输血的阴性对照组；（II）用改良牛Hb溶液替代40%总血容量（TBV）的阳性对照组；（III）实验组，在输注与II组相同体积的Hb溶液前4天及后3天，通过饮水给予每日剂量为5微克/千克体重的膳食补充硒（亚硒酸钠）。注射Hb溶液3天后，处死所有动物。通过测量灌注肝脏、心脏、肺、肾脏、脑匀浆及血浆中的共轭二烯（CD）和硫代巴比妥酸反应物（MDA）来确定氧化应激。此外，检测器官匀浆和血浆45k×g上清液中的抗氧化酶活性：超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）以及还原型谷胱甘肽（GSH）的细胞内水平。同时，还进行了非蛋白结合细胞内游离铁（Fe）和组织硒浓度的测量。同时，通过测量血浆乳酸脱氢酶（LDH）、谷丙转氨酶（SGPT）、肌酐、动脉血氧分压（PaO2）以及组织病理学研究来评估重要器官的损伤功能。结果表明，用Hb溶液进行换血输血显著增加了CD和MDA的形成，尤其是在肝脏和心脏组织以及血浆中。虽然肝脏和心脏组织中SOD和CAT的值普遍改变，但SOD/CAT比值也增加。注射Hb后，GSH-Px的活性保持不变，且与GSH的显著消耗有关。血浆中SGPT和LDH水平升高，但肌酐和PaO2与对照组相似，且与组织病理学结果相符。发现肝脏和心脏细胞内游离铁高于对照组。硒治疗对预防Hb引起的氧化损伤非常有效。在肝脏组织中观察到对MDA形成的完全保护（p<0.001）。此外，血浆中MDA、SGPT和LDH水平显著降低，且与对照组（I）相似。硒治疗增加了肝脏（p<0.05）和血浆（p<0.1）中GSH-Px的水平。（摘要截选至400字）
