Testicular creatine and urinary creatine-creatinine profiles in mice after the administration of the reproductive toxicant methoxyacetic acid.

It was previously observed that the acute or subchronic administration of some testicular toxicants, caused a significant raise in urinary creatine in rats. The aim of this study was to verify whether creatinuria could be detected in mice (a species with a different excretion profile of creatine) and whether it could be correlated to the levels of creatine in testis and to other parameters of testicular toxicity. The well known testicular toxicant methoxyacetic acid (MAA) was orally administered as a single dose (400 or 600 mg kg(-)) to male adult mice B6C3F1. Twenty-four hours after dosing, urinary creatine and creatinine showed a significant reduction with respect to the pre-treatment values. At the following times post-dosing (48 and 72 h) the creatine exceeded the control and pre-treatment values, while creatinine had not yet recovered. The ratio creatine/creatinine was significantly higher than control and pre-treatment values, at 24 and 48 h after the treatments. In testis a significant, dose-dependent, decrease of creatine was observed 24 h after dosing, with a pattern related to the histopathologic alterations observed at different times after the treatments. Creatine determination was the earlier quantitative parameter of testicular toxicity, since at this time testis weights, sperm head number and enzyme activities (LDH-C4, SDH) were less affected, their maximum decrease being reached at 14 days after the treatments. These data suggest that in mice, 2-MAA could interfere with the metabolism of creatine, both in testis and other biosynthetically active tissues.