Effect of various oestrogens on cell injury and alteration of apical transporters induced by tert-butyl hydroperoxide in renal proximal tubule cells

1. The present study was undertaken in order to examine the effect of various oestrogens on tert-butyl hydroperoxide (t-BHP)-induced cell injury and changes in apical transporters in primary cultured rabbit renal proximal tubule cells. 2. Compared with control, t-BHP (0.5 mmol/L; 1 h) decreased cell viability (62%) and glutathione (GSH) content (60%) and increased lipid peroxide (LPO) formation (309%), arachidonic acid (AA) release (193%) and Ca2+ influx (168%). 3. The protective potency of various oestrogens for these parameters is dependent on the precise oestrogenic structure, with 2-hydroxy-oestradiol-17beta (2-OH-E-2) and 4-OH-E-2, both catecholic oestrogens, or diethylstilbesterol (DES) being more potent than oestradiol (E-2), oestriol or oestradiol-17alpha, all phenolic oestrogens (P < 0.05). 4. These cytoprotective effects of oestrogens occur at concentrations above 10 mumol/L and are not dependent on classical oestrogen receptors and gene transcription and translation. In addition, various oestrogens have different preventative effects against t-BHP-induced inhibition of [C-14]-alpha-methyl-D-glucopyranoside (alpha-MG), inorganic phosphate (Pi) and Na+ uptake, consistent with the results of cell injury. In contrast, the potency against t-BHP-induced changes in cell viability, LPO, GSH content and transporter function of the anti-oxidants taurine and vitamin C is similar to that of phenolic oestrogens, whereas that of the iron chelators deferoxamine and phenanthroline is similar to that of catecholic oestrogens. 5. In conclusion, various oestrogens have differential cytoprotective potential against t-BHP-induced cell injury and decreases in alpha-MG, Na+ and Pi uptake. These effects are due, in part, to both the basic chemical properties of the compounds and the maintenance of endogenous GSH or inhibition of AA release and Ca2+ influx.