The effect of extracellular acidosis on different types of cell injury and death was examined using suspensions of rabbit renal proximal tubules. Cell death produced by the mitochondrial inhibitors rotenone, antimycin A, carbonyl cyanide p-trifluoromethoxyphenylhydrazone and oligomycin and by the ion exchangers valinomycin, nigericin and monensin was ameliorated by reducing extracellular pH (pH(e)) from 7.4 to 6.4. The protection lasted for more than 5 hr and was not due to the release of mitochondrial inhibition or to the maintenance of tubular ATP levels. In contrast, extracellular acidosis potentiated the cell injury and death produced by the oxidants t-butyl hydroperoxide, H2O2 and ochratoxin A. Because a decrease in pH(e) resulted in an increase in lipid peroxidation and in glutathione disulfide formation, and caused a decrease in glutathione peroxidase and glutathione reductase activities, the mechanism of this potentiation is most likely the result of an increase in free-radical production or a decrease in free-radical detoxification. The findings with the oxidants are in marked contrast to those in hepatocytes. These results show that renal cell death as a consequence of mitochondrial inhibition is sensitive to the protective effects of extracellular acidosis and that the effects of extracellular acidosis on cell death are dependent on the mechanism of injury.
|Original language||English (US)|
|Number of pages||6|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1993|
ASJC Scopus subject areas
- Molecular Medicine