ANTIOXIDATIVE PROPERTIES OF ORGANOTELLURIUM COMPOUNDS IN CELL SYSTEMS

The protective/antioxidative properties of diaryl tellurides were demo nstrated in cellular systems of increasing complexity. In the presence of glutathione, bis(4-hydroxyphenyl) celluride (1a), bis(4-aminopheny l) telluride (1d) and bis(2-carboxyphenyl) telluride (1h) reduced by m ore than 50% t-butyl hydroperoxide-induced cell death in lung fibrobla st cultures at concentrations below 2 mu M Bis(2,6-dimethyl-4-hydroxyp henyl) telluride (2b) reduced by more than 50% leukocyte-mediated and phorbol-12-myristate-13-acetate-stimulated damage to Caco-2 cells at 0 .1 mu M concentration. As judged by their abilities to reduce formatio n of thiobarbituric acid reactive substances at concentrations close t o 1 mu M, diaryl tellurides 1a, 1d and 2b protected rat kidney tissue against oxidative damage caused by anoxia and reoxygenation. The organ otellurium compounds also offered protection after systemic administra tion. In the presence of diaryl telluride 2b (0.1-1 mu M), the ischemi a/reperfusion-induced vascular permeability increase in the hamster ch eek pouch was significantly reduced as compared with the control. Some of the most active organotellurium cell protectants were evaluated fo r their ability to inhibit formation of the inflammatory mediators leu kotriene B-4 and interleukin-1 beta. An inhibitory effect on the secre tion of these species was seen for compounds 1a and 2b at or above 10 mu M concentrations. The protective effects of diaryl tellurides again st t-butyl hydroperoxide-induced cell injury can be ascribed mainly to the peroxide-decomposing, glutathione peroxidase-like capacity of the compounds. The chain-breaking, electron-or hydrogen atom-donating abi lity of diaryl tellurides seems to be the main reason for their protec tion against leukocyte-mediated cell damage in Caco-2 cells and in the oxidatively challenged rat kidney and hamster cheek pouch. (C) 1998 E lsevier Science Inc.