Urinary creatine profiles after administration of cell-specific testicular toxicants to the rat.
Cell-specific testicular toxicants have been used to examine the distribution of creatine within the rat testis, and to examine the potential use of creatinuria as a non-invasive indicator of testicular damage. Groups of rats were administered single doses of various toxicants: a germ cell toxicant (methoxyacetic acid, MAA), one of two Sertoli cell toxicants (di-n-pentyl phthalate, DPP or 1,3-dinitrobenzene, 1,3-DNB), or a Leydig cell toxicant (ethane-1,2-dimethane sulphonate, EDS). Urinary creatine and creatinine levels were monitored in 24 h periods over the following 48 h, after which time the testes were removed, weighed and, after processing, sections were examined by light microscopy. All four treatments resulted in reductions in relative testis weight (RTW) and produced morphological changes similar to those which have been previously reported. In addition, MAA, DPP and 1,3-DNB all caused significant elevations in urinary creatine excretion and the urinary creatine:creatinine ratio (Cr/Crn) within 24 h. EDS had no such effect. We conclude that creatine is associated with the cells of the seminiferous epithelium, and that elevated urinary excretion of creatine may serve as a non-invasive marker for damage to these cells in vivo.
Moore
N P
NP
Toxicology Unit, School of Pharmacy, University of London, UK.
Creasy
D M
DM
Gray
T J
TJ
Timbrell
J A
JA
D000085:Acetates / Q000633:toxicity*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003401:Creatine / Q000652:urine*; D004136:Dinitrobenzenes / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D008297:Male; D008698:Mesylates / Q000633:toxicity; D010795:Phthalic Acids / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012708:Sertoli Cells / Q000187:drug effects*
D000085:Acetates; D004136:Dinitrobenzenes; D008698:Mesylates; D010795:Phthalic Acids; C034171:di-n-pentyl phthalate; C017906:3-dinitrobenzene; C002994:ethylene dimethanesulfonate; C013598:methoxyacetic acid; D003401:Creatine