Renal proximal tubule segment-specific nephrotoxicity: An overview on biomarkers and histopathology
Renal proximal tubule segment-specific nephrotoxicity: An overview on biomarkers and histopathology
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DOI：
10.1080/01926230601187430
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发表时间：
2007-01-01
影响因子：
1.5
通讯作者：
Trevisan, Andrea
中科院分区：
文献类型：
--
作者：
Cristofori, Patrizia;Zanetti, Edoardo;Trevisan, Andrea
在用节段特异性肾毒物处理的大鼠中研究了组织病理学结果与节段特异性生物标志物之间的对应关系。雄性Wistar大鼠接受了单次注射K2 Cr2 O 7（25毫克/千克，皮下注射，溶于生理盐水）、顺式铂（10毫克/千克，腹腔注射，溶于MSO缓冲液）或六氯丁二烯（100毫克/千克，腹腔注射，溶于玉米油）。处理后24和48小时，处死大鼠，取出肾脏进行组织病理学和生物化学评价，即，肾皮质GS活性和肾皮质切片PAH摄取。组织学结果显示，顺式铂和六氯丁二烯分别引起外髓外条近端小管S-3段弥漫性坏死。相反，K_2Cr_2O_7仅损伤S-1-S-2节段，在处理后24小时诱导空泡化，48小时诱导弥漫性坏死。六氯丁二烯和顺式铂处理后，肾组织中的GS活性显著降低，但K2 Cr2 O 7处理后则没有。相比之下，K2 Cr2 O 7会显著降低多环芳烃的吸收，但顺式铂或六氯丁二烯处理不会降低多环芳烃的吸收（即使六氯丁二烯在处理后48小时略有降低）。本研究的证据证实了GS活性作为S-3段损伤标志物的高度特异性，PAH摄取在S-1-S-2段中是优先活性的，并且在段特异性肾毒物、段特异性损伤的生物标志物和组织病理学发现之间存在完全对应。
The correspondence between histopathological findings and segment-specific biomarkers was investigated in rats treated with segment-specific nephrotoxicants. Male Wistar rats were treated with a single injection of K2Cr2O7 (25 mg/kg sc in saline), cis-Pt (10 mg/kg ip in buffered MSO) or HCBD (100 mg/kg ip in corn oil). Twenty-four and 48 hours after treatment, the rats were sacrificed and the kidneys were drawn for histopathological and biochemical evaluation, i.e., GS activity in renal cortex and PAH uptake in renal cortical slices. Histopathological findings show that cis-Pt and HCBD cause diffuse necrosis of S-3 segment of proximal tubules in the outer stripe of outer medulla, respectively. On the contrary, K2Cr2O7 damages exclusively S-1-S-2 segments, inducing vacuolization at 24 hr and diffuse necrosis at 48 hr after treatment. GS activity in renal tissue is significantly decreased after HCBD and cis-Pt, but not K2Cr2O7 treatment. In contrast, PAH uptake is significantly reduced by K2Cr2O7, but not by cis-Pt or HCBD treatment (even if HCBD causes a slight decrease 48 hr after treatment). The evidence of this study confirms the high specificity of GS activity as marker of S-3 segment injury, that PAH uptake is prevalently active in the S-1-S-2 Segments, and that there is complete correspondence among segment-specific nephrotoxicants, biomarkers of segment-specific damage, and histopathological findings.