LLU-alpha, an endogenous metabolite of gamma-tocopherol, is more effectiveagainst metal nephrotoxicity in rats than gamma-tocopherol

Antioxidants of the vitamin E family have protective effects against metal toxicity. We examined the protective effect of racemic LLU-alpha [2,7,8-tri methyl-2-(carboxyethyl)-6-hydroxychroman] a metabolite of gamma -tocopherol , in comparison to the effect of alpha- and gamma -tocopherol in rats treat ed with sodium dichromate (Cr) or thallium sulfate (Tl). We measured metal nephrotoxicity based on urinary protein excretion and discussed it with res pect to the metal concentration in renal tissue. The ranking of antioxidant activity (iron Stimulated lipid peroxidation, luminol and lucigenin amplif ied chemiluminescence) was determined in the following order: alpha -tocoph erol < gamma -tocopherol < LLU-alpha. Pretreatment with LLU-alpha produced lower chromate nephrotoxicity than alpha- or gamma -tocopherol. but did not influence Cr concentration in renal tissue. The protective effect of LLU-a lpha against Cr toxicity seemed to be caused by its stronger antioxidant ac tivity in comparison to alpha- and gamma -tocopherol. Pretreatment with LLU -alpha resulted in lower thallium-induced proteinuria, a lower concentratio n of Tl in the renal medulla, and higher urinary Tl excretion. Unlike LLU-a lpha, which has been shown to inhibit K+ channels in the apical membrane of the thick ascending limb of Henle's loop, we found that gamma -tocopherol did not. This finding reaffirmed the similarity between K- and Tl+ and also explained the significantly decreased Tl concentration in the renal medull a in rats treated with LLU-alpha. We speculate that the protective effect o f LLU-alpha against Tl nephrotoxicity is caused both by its antioxidant eff ect and, at least in part, by its ability to decrease Tl concentration as a consequence of inhibited Tl+ uptake through K+ channels. This finding conf irmed the similarity between K+ and Tl+ and also explained the significantl y decreased Tl concentration in the renal medulla in rats treated with LLU- alpha. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.