Dehpour A R, Essalat M, Ala S, Ghazi-Khansari M, Ghafourifar P
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
Toxicology. 1999 Feb 15;132(2-3):119-25. doi: 10.1016/s0300-483x(98)00143-7.
Urinary N-acetyl-beta-D-glucosaminidase (NAG) had been shown to be a useful early marker of renal injury such as lead nephrotoxicity. This study investigated the effect of lead acetate on nephrotoxicity and its correlation with the nitric oxide (NO) system by determining the NAG release in perfused rat kidney. Lead acetate caused a time and concentration-dependent increase in enzymuria. The effect of concurrent perfusion with lead and L-arginine (L-arg) or L-N(G)-nitro arginine methyl ester (L-NAME) [substrate and inhibitor of NO synthase respectively] in the perfusion fluid was also studied by measuring NAG activity in the perfusate kidney rat. L-arg (2 mM) has significantly decreased the lead-induced NAG release (P < 0.001), and L-NAME (0.1 mM) has significantly increased the lead-induced enzyme release in a time-dependent manner (P < 0.001). Moreover, histological studies using light microscope showed that some of the epithelial cells of the proximal convoluted tubules are degenerated or necrotic and desquamated into the lumens in rat treated with lead acetate. This change occurs at 50 microg/dl of lead acetate and was increased by addition of L-NAME to lead acetate. However, addition of L-arg had no effect on histology of lead nephrotoxicity. This may suggest that lead may interfere with the NO system in rat kidney.
尿N-乙酰-β-D-氨基葡萄糖苷酶（NAG）已被证明是肾损伤如铅肾毒性的一种有用的早期标志物。本研究通过测定灌注大鼠肾脏中的NAG释放，研究了醋酸铅对肾毒性的影响及其与一氧化氮（NO）系统的相关性。醋酸铅导致酶尿呈时间和浓度依赖性增加。通过测量灌注液中大鼠肾脏的NAG活性，还研究了在灌注液中同时灌注铅与L-精氨酸（L-arg）或L-N（G）-硝基精氨酸甲酯（L-NAME）[分别为NO合酶的底物和抑制剂]的效果。L-arg（2 mM）显著降低了铅诱导的NAG释放（P < 0.001），而L-NAME（0.1 mM）以时间依赖性方式显著增加了铅诱导的酶释放（P < 0.001）。此外，使用光学显微镜的组织学研究表明，在用醋酸铅处理的大鼠中，一些近曲小管的上皮细胞发生变性、坏死并脱落到管腔中。这种变化在醋酸铅浓度为50微克/分升时出现，并因向醋酸铅中添加L-NAME而加剧。然而，添加L-arg对铅肾毒性的组织学没有影响。这可能表明铅可能干扰大鼠肾脏中的NO系统。
