DIFFERENCE IN H2O2 TOXICITY BETWEEN INTACT RENAL TUBULES AND CULTUREDPROXIMAL TUBULAR CELLS

The present study was undertaker, to examine the response to H2O2 and t-butylhydroperoxide (t-BHP) in various in vitro model systems of rena l proximal tubules: rabbit renal cortical slices, freshly isolated rab bit proximal tubules, rabbit primary cultured proximal tubular cells, and opossum kidney (OK) cells. t-BHP increased lactate dehydrogenase r elease and lipid peroxidation in a concentration-dependent manner over the concentration range of 0.2 to 3 mM in cortical slices, whereas H2 O2 caused a similar concentration-dependent increase in both parameter s at 5-100 mM. The sensitivity of isolated tubules to both peroxides w as similar to that of cortical slices. In primary cultured cells and O K cells, however, the cytotoxicity of H2O2 was identical to that of t- BHP. The cytotoxicity of t-BHP was not different among all the systems examined. The specific activity of catalase in cortical slices was si milar to that of isolated tubules, but it was much higher than that of primary cultured cells or opossum kidney cells. Glutathione (GSH) per oxidase activity was not different among all the systems examined. The expression of catalase mRNA in cortical slices and isolated tubules w as higher than that in primary cultured cells, whereas those of supero xide dismutase, glutathione peroxidase, or beta-actin were not differe nt among the systems. These results indicate that intact proximal tubu les are more resistant to H2O2 than are cultured proximal tubular cell s, and the resistance is due to a higher specific activity of catalase resulting from the increased expression of its mRNA. BIOCHEM PHARMACO L 56;4:489-495, 1998. (C) 1998 Elsevier Science Inc.