Folic acid induces acute renal failure (ARF) by enhancing renal prooxidant state
Folic acid induces acute renal failure (ARF) by enhancing renal prooxidant state
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DOI：
10.1016/j.etp.2010.08.010
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发表时间：
2012-03-01
影响因子：
--
通讯作者：
Puri, Sanjeev
中科院分区：
文献类型：
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作者：
Gupta, Anuj;Puri, Veena;Puri, Sanjeev
用叶酸（FA）对小鼠进行全身给药，研究其与急性肾功能衰竭（ARF）相关的发病机制。然而，FA诱导ARF的机制仍然知之甚少。因此，本研究计划研究叶酸给药对促氧化状态和肾组织相关超微结构变化的影响。将4-6周龄的BalB/c雄性小鼠分为对照组和两个叶酸处理组（A组和B组）。A组动物连续7天腹腔注射叶酸（100 mg/kg体重），而B组动物腹腔注射叶酸（250 mg/kg体重）。收集肾组织，用于肾组织脂质过氧化指标和抗氧化酶活性的分析。为了证实肾组织中的生化发现，研究了扫描电子显微镜（SEM）。叶酸处理的动物表现出明显的肾肥大，伴有肾功能严重受损。FA处理后，SOD、CAT、GSH-Px、GSH水平显著降低，LPO水平显著升高。SEM结果进一步证实了所观察到的生化变化，如肾小球中的严重炎症、初级和次级蒂中的肿胀、绒毛中的起泡以及FA处理的肾脏中的红细胞（RBC）的巨大剥夺所证明的。因此，目前的研究表明，叶酸急性给药导致氧化应激的产生和改变膜结构负责叶酸诱导的ARF。(C)2010年Elsevier GmbH。All rights reserved.
Systemic administration of folic acid (FA) in mice was used for studying the pathogenesis associated with acute renal failure (ARF). However, the mechanism by which FA induces ARF remains poorly understood. The present study therefore, was planned to investigate the effect of folic acid administration on prooxidant state and associated ultrastructural changes in renal tissue. Balb/c male mice of 4-6 weeks old were divided into control and two folic acid treatment groups (Groups A and B). The animals in group A were administered intraperitoneal injection of folic acid (100 mg kg(-1) body weight) for a period of 7 consecutive days while the animal in group B were administered a single intraperitoneal dose of folic acid (250 mg kg(-1) body weight). The renal tissues were collected and used for the analyses of lipid peroxidative indices and activities of antioxidant enzymes in renal tissues. To corroborate biochemical findings scanning electron microscopy (SEM) in renal tissue was studied. Folic acid treated animals demonstrated marked renal hypertrophy accompanied by severe impairment of renal function. Glutathione levels (GSH) and antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) levels were significantly decreased and LPO levels increased following FA treatment. SEM results further substantiated the observed biochemical changes as evident by severe inflammation in glomeruli, swelling in primary and secondary pedicels, blebbing in villi, and tremendous deprivation of erythrocytes (RBCs) in FA treated kidneys. The present study therefore suggests that acute administration of folic acid leads to the generation of oxidative stress and altered membrane architecture responsible for folic acid induced ARF. (C) 2010 Elsevier GmbH. All rights reserved.