Production of Methylguanidine from Creatinine in Normal Rats and Rats with Renal Failure

Abstract

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/l00 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 μg/ 100 g body weight) than in normal rats (70.30 μg/l00 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.

Methylguanidine cytotoxicity on HK-2 cells and protective effect of antioxidants against MG-induced apoptosis in renal proximal tubular cellsin vitro

“…Some experiments revealed that animals with high-level MG displayed a lot of functional and pathological characteristic features of uremia. 12,13 Another study showed significant reduction of the glomerular filtration rate, renal plasma flow, and renal blood flow after administration of MG to normal rats 14 and rats with adenine-induced chronic renal failure. 15 Thus, MG has apparent toxic effects on kidney and causes deterioration of renal function, but the pathogenesis is still not very well understood.…”

Increase in Kidney 8-Hydroxydeoxyguanosine Level with the Progression of Renal Failure

“…Normal animals were fed on an 18% casein diet for 10 days. In rats given adenine, it had been confirmed previously both histologically and biochemi cally that renal failure progressed as the peri od of adenine feeding was prolonged [16][17][18][19][20][21][22][23]. The level of serum constituents in experimen tal rats were as follows: in rats fed on the adenine diet, urea nitrogen levels were 3.2 times (50.5 ±1.5 mg/dl) those in normal rats on the 10th experimental day, and 8.6 times higher on the 30th experimental day.…”

Biodistribution of 99m technetium- labeled creatinine in healthy rats

“…It seems that the normal brain content of creatinine is very low but increases considerably in the presence of an extra creatinine load. Creatinine levels have been found to be increased in the brain of both uremic persons and experimental animals, with the latter suffering convulsions after intraperitoneal injection of creatinine (18,19). The uptake of 99m Tc-creatinine in blood did not change significantly during the present study, possibly due to a balanced exchange of creatinine between blood and tissues.…”