Laboratory of Biochemistry, UR03/ES-08 Human Nutrition and Metabolic Disorders, Faculty of Medicine, Monastir, Tunisia.
Toxicol Mech Methods. 2012 Nov;22(9):696-704. doi: 10.3109/15376516.2012.717650.
The present study evaluated the effects of sub-acute exposure to different doses of 2,4-dichlorophenoxyacetic acid (2,4-D) on rat kidney. Forty animals were divided into four equal groups and treated with different doses of 2,4-D: 0, 15, 75 and 150 mg/kg body weight per day via oral gavage for 28 consecutive days. Renal function, histopathology, tissue malondialdehyde and antioxidant enzyme activities were evaluated. The results showed a significant decrease (p < 0.01) in uric acid level and an increase in plasma levels of urea and creatinine (p < 0.01) in rats administered 2,4-D at the three studied doses. The activities of catalase and superoxide dismutase were significantly affected for all treated rats, while glutathione peroxidase significantly decreased in rats exposed to 2,4-D at a dose of 150 mg/kg. Through sub-acute treatment, starting from the low to the high doses of 2,4-D, there were significant increase in kidney MDA as compared to controls. The histopathological study revealed tubular damages, glomerular alterations, vascular congestion and increased number of pyknotic nuclei in kidneys of all 2,4-D treated groups. The severity of these alterations increase in a dose-dependent manner. Our findings confirm that sub-acute exposure to 2,4-D induced oxidative renal dysfunction in rats. Therefore, at higher doses, 2,4-D may be implicated in the pathogenesis of kidney failure via lipid peroxidation and oxidative stress.
本研究评估了亚急性接触不同剂量 2,4-二氯苯氧乙酸（2,4-D）对大鼠肾脏的影响。将 40 只动物分为四组，每组 10 只，分别用不同剂量的 2,4-D 经口灌胃：0、15、75 和 150mg/kg 体重，连续 28 天。评估肾功能、组织丙二醛和抗氧化酶活性。结果显示，与对照组相比，经口给予 2,4-D 三个研究剂量后，尿酸水平显著降低（p<0.01），尿素和肌酐的血浆水平升高（p<0.01）。所有处理组的过氧化氢酶和超氧化物歧化酶活性均受到显著影响，而接触 150mg/kg 2,4-D 的大鼠谷胱甘肽过氧化物酶活性显著降低。通过亚急性处理，2,4-D 从低剂量到高剂量，与对照组相比，肾脏 MDA 显著增加。组织病理学研究显示，所有 2,4-D 处理组的肾小管损伤、肾小球改变、血管充血和核固缩增加。这些改变的严重程度呈剂量依赖性增加。我们的研究结果证实，亚急性接触 2,4-D 导致大鼠肾脏氧化功能障碍。因此，在较高剂量下，2,4-D 可能通过脂质过氧化和氧化应激参与肾衰竭的发病机制。
