Guanidinoacetic acid (GAA) synthesis in rat tubular suspension as a system for evaluating gentamicin (GM) nephrotoxicity.
Since guanidinoacetic acid (GAA), a precursor of creatine, is synthesized mainly in the proximal tubule of the kidney where gentamicin (GM) nephrotoxicity often occurs, GM-induced renal cell damage was investigated using GAA synthesis in tubular suspension as an indicator. Results obtained were as follows: (1) GAA synthesis was significantly suppressed with 1 mM GM; (2) GM-induced decrease in GAA synthesis was recognized during incubation longer than 15 min; (3) furosemide significantly enhanced the suppression of GAA synthesis by GM. The results obtained parallel with those in the whole animal thus making GAA synthesis in tubular suspension a valid system for evaluating the GM-induced proximal tubular damage.
Takeda
M
M
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Jung
K Y
KY
Sekine
T
T
Endou
H
H
Koide
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004232:Diuretics / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000633:toxicity; D005839:Gentamicins / Q000633:toxicity*; D005998:Glycine / Q000031:analogs & derivatives* / Q000096:biosynthesis; D066298:In Vitro Techniques; D007674:Kidney Diseases / Q000139:chemically induced*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D000900:Anti-Bacterial Agents; D004232:Diuretics; D005839:Gentamicins; D005665:Furosemide; C004946:glycocyamine; D005998:Glycine