Production of methylguanidine from creatinine in normal rats and rats with renal failure

Creatinine (Cr) was administered intraperitoneally to both normal rats and those given adenine, and time-course changes in methylguanidine (MG) production from Cr were compared. In rats with renal failure, the accumulation of MG in the body increased gradually with time after Cr administration. In particular, the MG level in skeletal muscle was markedly high in comparison with that in serum, liver or kidney, and a high concentration of MG was still present 24 h after Cr loading. In contrast, the amount of MG excreted into urine in these rats during 24 h after Cr administration was lower than the corresponding values in normal rats. Thus, the amount of MG per rat, distributed at 24 h after intraperitoneal administration of Cr 300 mg/100 g body weight was calculated. The production of MG from Cr was found to be markedly higher in rats with adenine-induced renal failure (172.09 micrograms/100 g body weight) than in normal rats (70.30 micrograms/100 g body weight). Produced MG was mostly excreted into urine in normal rats, whereas in rats with renal failure as much as 79.1% of produced MG was accumulated in the body.