CHANGES IN SERUM LEVELS OF CREATOL AND METHYLGUANIDINE IN RENAL INJURY-INDUCED BY LIPID PEROXIDE PRODUCED BY VITAMIN-E-DEFICIENCY AND GSH DEPLETION IN RATS

A novel creatinine metabolite, creatol (5-hydroxycreatinine), is a key precursor in the synthesis of the uremic toxin methylguanidine (MG). Creatinine is converted to creatol within the mammalian body and this conversion is mediated specifically by hydroxyl radicals. We investiga ted the production of creatol and MG from creatinine in rats with rena l failure induced by the lipid peroxide produced as a consequence of v itamin E deficiency and depletion of the reduced form of glutathione ( GSH). In addition, we examined serum levels of other guanidino compoun ds, namely guanidinoacetic acid (GAA) and guanidinosuccinic acid (GSA) . The injury to kidneys induced by the depletion of GSH in combination with vitamin E deficiency caused markedly elevated serum levels of cr eatol, MG and GSA and decreased serum GAA. The molar ratio of creatol to creatinine in the serum, which should be an index of the oxygen str ess mediated by hydroxyl radicals, increased with time. Therefore, the enhanced production of creatol in vitamin-E-deficient rats that have been depleted of GSH might be due to the enhanced production of oxygen radicals in this system.