Troncoso P, Smok G, Videla L A
Department of Biochemistry, Faculty of Medicine, University of Chile, Santiago, Chile.
Free Radic Biol Med. 1997;23(1):19-25. doi: 10.1016/s0891-5849(96)00575-8.
Parameters related to hepatic oxidative stress, cell injury, and liver histology were determined in control rats and in animals treated with 3,3',5-triiodothyronine (T3), after in vitro perfusion under normoxic or ischemia-reperfusion conditions. Thyroid calorigenesis was found concomitantly with higher rates of hepatic O2 consumption and thiobarbituric acid reactive substances (TBARS) formation, glutathione (GSH) depletion, enhanced TBARS/GSH ratio as indicator of oxidative stress, and higher sinusoidal lactate dehydrogenase (LDH) efflux compared to control values, assessed under normoxic conditions. Perfused livers from control animals subjected to ischemia-reperfusion exhibited significant increases in the TBARS/GSH ratio and in the sinusoidal LDH efflux over values obtained under normoxic conditions, concomitantly with the appearance of small foci of necrotic cells in centrilobular and midzonal areas of the liver lobule. These parameters were further modified in the liver of hyperthyroid rats subjected to ischemia-reperfusion, with elevations in the TBARS/GSH ratio and in the sinusoidal LDH efflux largely exceeding the sum of effects elicited by hyperthyroidism or ischemia-reflow alone. In this situation, liver injury was more pronounced than in control rats, being characterized by multifocal areas of necrotic cells, irregularly distributed in the hepatic lobule, with lymphoid and macrophagic reaction. It is concluded that the concurrence of the hepatic mechanisms related to the oxidative stress underlying thyroid calorigenesis and ischemia-reoxygenation exacerbates liver injury, which seems to be mediated by potentiation of the prooxidant state of the organ.
在常氧或缺血再灌注条件下进行体外灌注后，测定了对照大鼠以及用3,3',5-三碘甲状腺原氨酸（T3）处理的动物的肝氧化应激、细胞损伤和肝脏组织学相关参数。与对照值相比，在常氧条件下评估发现，甲状腺产热伴随着肝脏耗氧率和硫代巴比妥酸反应性物质（TBARS）生成率升高、谷胱甘肽（GSH）耗竭、作为氧化应激指标的TBARS/GSH比值升高以及肝窦乳酸脱氢酶（LDH）外流量增加。对照动物的灌注肝脏在缺血再灌注后，与常氧条件下获得的值相比，TBARS/GSH比值和肝窦LDH外流量显著增加，同时在肝小叶的中央小叶和中区出现小灶性坏死细胞。在缺血再灌注的甲状腺功能亢进大鼠肝脏中，这些参数进一步改变，TBARS/GSH比值和肝窦LDH外流量升高，大大超过单独由甲状腺功能亢进或缺血再灌注引起的效应之和。在这种情况下，肝脏损伤比对照大鼠更明显，其特征是坏死细胞多灶性区域，不规则地分布在肝小叶中，并伴有淋巴细胞和巨噬细胞反应。结论是，与甲状腺产热和缺血再氧合潜在的氧化应激相关的肝脏机制同时存在会加剧肝脏损伤，这似乎是由器官促氧化状态的增强介导的。
