LLU-α, an endogenous metabolite of γ-tocopherol, is more effective against metal nephrotoxicity in rats than γ-tocopherol

Abstract

Antioxidants of the vitamin E family have protective effects against metal toxicity. We examined the protective effect of racemic LLU-α [2,7,8-trimethyl-2-(carboxyethyl)-6-hydroxychroman] a metabolite of γ-tocopherol, in comparison to the effect of α- and γ-tocopherol in rats treated with sodium dichromate (Cr) or thallium sulfate (Tl). We measured metal nephrotoxicity based on urinary protein excretion and discussed it with respect to the metal concentration in renal tissue. The ranking of antioxidant activity (iron stimulated lipid peroxidation, luminol and lucigenin amplified chemiluminescence) was determined in the following order: α-tocopherol<γ-tocopherol<LLU-α. Pretreatment with LLU-α produced lower chromate nephrotoxicity than α- or γ-tocopherol, but did not influence Cr concentration in renal tissue. The protective effect of LLU-α against Cr toxicity seemed to be caused by its stronger antioxidant activity in comparison to α- and γ-tocopherol. Pretreatment with LLU-α resulted in lower thallium-induced proteinuria, a lower concentration of Tl in the renal medulla, and higher urinary Tl excretion. Unlike LLU-α, which has been shown to inhibit K + channels in the apical membrane of the thick ascending limb of Henle's loop, we found that γ-tocopherol did not. This finding reaffirmed the similarity between K + and Tl + and also explained the significantly decreased Tl concentration in the renal medulla in rats treated with LLU-α. We speculate that the protective effect of LLU-α against Tl nephrotoxicity is caused both by its antioxidant effect and, at least in part, by its ability to decrease Tl concentration as a consequence of inhibited Tl + uptake through K + channels. This finding confirmed the similarity between K + and Tl + and also explained the significantly decreased Tl concentration in the renal medulla in rats treated with LLU-α.