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

Abstract

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 investigated the production of creatol and MG from creatinine in rats with renal failure induced by the lipid peroxide produced as a consequence of vitamin E deficiency and depletion of the reduced form of glutathione (GSH). In addition, we examined serum levels of other guanidino compounds, 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 creatol, 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 stress 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.