Nephrotoxicity induced by adenine and its analogs: relationship between structure and renal injury.
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.
Minami
T
T
Faculty of Pharmaceutical Sciences, Kinki University, Osaka, Japan.
Nakagawa
H
H
Nabeshima
M
M
Kadota
E
E
Namikawa
K
K
Kawaki
H
H
Okazaki
Y
Y
D000225:Adenine / Q000031:analogs & derivatives* / Q000633:toxicity*; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship
D003404:Creatinine; D000225:Adenine