Valentovic M, Williams P, Carl J, Rankin G O
Department of Pharmacology, Marshall University School of Medicine, Huntington, WV 25755-9310.
J Appl Toxicol. 1994 Jul-Aug;14(4):281-5. doi: 10.1002/jat.2550140407.
The kidney has been identified as the specific target organ for in vivo exposure to an agricultural fungicide, N-(3,5-dichlorophenyl)succinimide (NDPS). The goal of this study was to determine if urinary protein and enzyme excretion were sensitive, non-invasive markers for NDPS-induced renal damage. The proximal tubular enzymes that were monitored were the brush-border enzyme alkaline phosphatase (ALP) and the lysosomal enzyme N-acetyl-beta-D-glucosaminidase (NAG). Male Fischer 344 (F344) rats were injected intraperitoneally (i.p.) with 0.2 or 1.0 mmol kg-1 NDPS. Control animals were injected i.p. with sesame oil (2.5 ml kg-1). Urine was collected on ice 0-3, 3-6 and 6-24 h after NDPS or vehicle injection. Urinary protein and urinary NAG excretion levels were elevated (P < 0.05) above the control levels 0-3 h after treatment with 0.2 mmol kg-1 NDPS. Urinary protein and enzyme excretion was comparable between 0.2 mmol kg-1 NDPS-treated and control groups for all other time periods. Administration of a marked nephrotoxicant dose (1.0 mmol kg-1) was associated with elevated levels of urinary protein, NAG and ALP beginning 0-3 h after treatment when compared to the control group or to respective baseline values. It was concluded from these studies that measurement of urinary protein as well as the release of ALP and NAG were sensitive markers of renal damage produced by NDPS.
肾脏已被确定为体内接触农用杀菌剂N-(3,5-二氯苯基)琥珀酰亚胺（NDPS）的特定靶器官。本研究的目的是确定尿蛋白和酶排泄是否为NDPS诱导的肾损伤的敏感、非侵入性标志物。所监测的近端肾小管酶为刷状缘酶碱性磷酸酶（ALP）和溶酶体酶N-乙酰-β-D-氨基葡萄糖苷酶（NAG）。雄性Fischer 344（F344）大鼠腹腔注射0.2或1.0 mmol kg-1的NDPS。对照动物腹腔注射芝麻油（2.5 ml kg-1）。在注射NDPS或赋形剂后0 - 3、3 - 6和6 - 24小时在冰上收集尿液。用0.2 mmol kg-1的NDPS处理后0 - 3小时，尿蛋白和尿NAG排泄水平高于对照水平（P < 0.05）。在所有其他时间段，0.2 mmol kg-1 NDPS处理组和对照组之间的尿蛋白和酶排泄相当。与对照组或各自的基线值相比，给予显著肾毒性剂量（1.0 mmol kg-1）与治疗后0 - 3小时开始的尿蛋白、NAG和ALP水平升高有关。从这些研究得出结论，尿蛋白的测量以及ALP和NAG的释放是NDPS产生的肾损伤的敏感标志物。
