Protective mechanism of sodium molybdate against the acute toxicity of cadmium in rats. II. Prevention of cytoplasmic acidification |
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Authors: | Toshiaki Koizumi Toshiki Yokota Mikiko Fukuchi Hideki Tatsumoto Yasuhiro Yamane |
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Affiliation: | (1) Department of Hygienic Chemistry Faculty of Pharmaceutical Sciences, Chiba University, Japan;(2) Department of Human Environmental Chemistry Faculty of Engineerings, Chiba University, Japan;(3) Dept. of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Chiba University, 1–33, Yayoi-Cho, 260 Chiba, Japan |
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Abstract: | In order to clarify the protective mechanism of sodium molybdate against the acute toxicity of cadmium chloride in rat, the effect of in vivo sodium molybdate pretreatment on the cytotoxic action of cadmium in isolated hepatocytes was studied. The cytosolic pH of hepatocytes isolated from untreated rats immediately decreased with incubation in either neutral Hank's balanced salt solution (HBS), pH 7.4, containing 5 µM cadmium chloride minimum or acidic HBS (pH 7.1, 6.8, 6.5, and 6.2). The presence of 5 µM cadmium in HBS adjusted to pH 7.1 aggravated cytosalic acidification induced by the acidic medium alone. Cell viability of hepatocytes incubated in HBS at pH 6.2 was significantly reduced as compared to that of control cells in HBS at pH 7.4, but the presence of cadmium in the acidic HBS had no aggravating action against such a toxic action of the acidic medium although cellular uptake of the metal in the medium increased, as compared to that in HBS at pH 7.4. Molybdenum pretreatment alleviated cytoplasmic acidification induced by the treatment with HBS at pH 7.4 or 7.1 containing cadmium or by extracellular acid load wothout cadmium. This pretreatment also prevented the loss of cell viability induced by the treatment with HBS at pH 6.2 but could not attenuate that when cadmium was present in the medium.These facts suggest that molybdenum pretreatment alleviated the acute toxicity of cadmium in rat by preventing cytoplasmic acidification caused by the harmful metal. |
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Keywords: | cadmium molybdenum intracellular pH Na+/H+ exchanger cellular acidification free cytosolic calcium |
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