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Year : 2000  |  Volume : 32  |  Issue : 2  |  Page : 120-125

Inhibition of Ca 2+ -ATPase and perturbation in Ca ++ homeostasis in rat liver on administration of methyl isocyanate

Correspondence Address:
K Jeevaratnam

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Source of Support: None, Conflict of Interest: None

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Objectives: To study the perturbations of calcium homeostasis by methyl isocyanate (MIC), if any. Methods: Hepatic microsomal Ca2+ -ATPase activity, Ca2+ and 45Ca distribution in serum and hepatic subcellular fractions were determined. Results: Addition of MIC in vitro resulted in dose-dependent inhibition of Ca2+ -ATPase. Subcutaneous administration of MIC at lethal dose caused a significant inhibition of Ca2+ -ATPase activity in vivo and significant changes in subcellular Ca 2+ distribution in rat liver as a result of an enhanced extracellular Ca2+ influx. The serum Ca2+ level was decreased. There was an enhanced cytosolic Ca2+ which was accumulated primarily in the mitochondria. In these rats, there was a significant increase in the mitochondrial pool of reduced glutathione (GSH) with a concomitant decrease in the cytosolic GSH. The isolated hepatic mitochondria of these rats showed significantly lower rates of calcium-stimulated respiration. Conclusion: This study suggests that the perturbations in the intracellular calcium homeostasis due to inhibition of Ca2+ -ATPase by MIC in rat liver could be one of the several factors associated with its cytotoxicity.


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