Key result
Single IV doxorubicin does not change mitochondrial calcium or magnesium content in rat hearts.
Why the study?
Abnormalities of mitochondrial divalent cation metabolism as early causative events in doxorubicin cardiotoxicity were uncertain.
Answers are grounded in this paper and cite their sources.
Animal data on early mitochondrial Ca/Mg shifts in DXR toxicity leave open causality and any clinical relevance.
The purpose of this study was to determine whether abnormalities of mitochondrial divalent cation metabolism are early, causative events in doxorubicin (DXR, Adriamycin) cardiotoxicity. We used electron probe microanalysis (EPMA) to examine the calcium (Ca) and magensium (Mg) content of in situ mitochondria in cryosections of rat hearts, rapidly frozen at 6 hr and 1, 3, and 5 days after a single iv injection of 20 mg/kg DXR. This dose produced 100% mortality in 7 days, with a mean survival of 5.8 days. Mean control mitochondrial Ca and Mg was 0.7 and 28 mmol/kg dry wt, respectively (+/- SEM), and did not change in the DXR-injected animals, even in severely symptomatic rats 5 days after DXR. This suggests that an alteration in mitochondrial divalent cation metabolism is unlikely to be a primary event in the pathogenesis of DXR-induced cardiotoxicity, and that the mitochondrial Ca accumulation demonstrated in previous studies represents a secondary event in cells damaged by another mechanism.
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Eckenhoff et al. (1989) studied Doxorubicin cardiotoxicity. Doxorubicin vs. Control was evaluated on Mitochondrial calcium and magnesium content. A single iv injection of 20 mg/kg doxorubicin did not change mean mitochondrial calcium (0.7 mmol/kg) or magnesium (28 mmol/kg) content in rat hearts compared to controls.
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