Minami T, Nakagawa H, Nabeshima M, Kadota E, Namikawa K, Kawaki H, Okazaki Y
Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Biol Pharm Bull. 1994 Aug;17(8):1032-7. doi: 10.1248/bpb.17.1032.
Twenty-four adenine analogs were administered to mice and the relationship between the structure of analogs and the occurrence of renal injury was examined. Plasma urea nitrogen (UN) and creatinine levels were measured 24 h after oral administration of analogs. Both levels increased in the adenine-, 8-azaadenine-, isoguanine-, or 6-dimethyl aminopurine (6-DMAP)-administered group, but did not increase in the other analog groups. From light microscopy, the damages of tubuli, mainly of proximal tubuli, were observed in the kidneys of these four groups. The common property of these compounds is the strong basicity of nitrogen which binds the 6-position of the purine ring. Furthermore, UN and creatinine increased time-dependently with intravenous administration of isoguanine. When adenine was intravenously administered, UN slightly increased at 1 h, but creatinine was unchanged. No changes were observed in the 6-DMAP- or 8-azaadenine-administered group. The basicity of nitrogen which binds to the 6-position of the purine ring is thus considered to be related to the occurrence of renal injury with oral administration, and isoguanine has high affinity with the kidney.
给小鼠施用了24种腺嘌呤类似物，并研究了类似物结构与肾损伤发生之间的关系。在口服类似物24小时后测量血浆尿素氮（UN）和肌酐水平。在给予腺嘌呤、8-氮杂腺嘌呤、异鸟嘌呤或6-二甲基氨基嘌呤（6-DMAP）的组中，这两个水平均升高，但在其他类似物组中未升高。通过光学显微镜观察，在这四组小鼠的肾脏中均观察到肾小管损伤，主要是近端肾小管损伤。这些化合物的共同特性是与嘌呤环6位结合的氮具有强碱性。此外，静脉注射异鸟嘌呤后，UN和肌酐水平呈时间依赖性升高。静脉注射腺嘌呤时，1小时时UN略有升高，但肌酐无变化。在给予6-DMAP或8-氮杂腺嘌呤的组中未观察到变化。因此，与嘌呤环6位结合的氮的碱性被认为与口服给药时肾损伤的发生有关，并且异鸟嘌呤对肾脏具有高亲和力。
