Creatinine (Cr), creatol and methylguanidine (MG), which accumulate in the body with the progress of renal failure after adenine administration, were given separately to rats in order to compare their toxicities. Food containing adenine was given to rats for 20 days to induce renal failure. Then each of the test substances was administered intraperitoneally, and renal function of the rats was determined. The changes in glomerular filtration rate, renal plasma flow and renal blood flow after administration of Cr were only slight in comparison with those of the control group. Creatol or MG administration induced a significant decrease in renal function. In addition, the level of MG in serum, liver and kidney was extraordinarily high in rats given creatol or MG. The toxic effects are discussed on the basis of these results.
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Yokozawa et al. (2008) studied this question.