Histochemical alterations of acute and chronic doxorubicin cardiotoxicity

• Published in: Journal of molecular and cellular cardiology Vol. 15; no. 8; pp. 543 - 553
• Main Authors: Aversano, Renee C., Boor, Paul J.
• Format: Journal Article
• Language: English
• Published: Kent Elsevier Ltd 01.08.1983; Elsevier
• Subjects: Animals; Biological and medical sciences; Calcium - metabolism; Cardiomyopathies - chemically induced; Cardiomyopathies - enzymology; Cardiomyopathy; Coenzyme Q 10; Creatine Kinase - metabolism; Cytochrome Oxidase; Dose-Response Relationship, Drug; Doxorubicin; Doxorubicin - toxicity; Drug toxicity and drugs side effects treatment; Enzymes - metabolism; Glutathione - metabolism; Histochemistry; Intracellular calcium; L-Lactate Dehydrogenase - metabolism; Male; Medical sciences; Mice; Mice, Inbred Strains; Mitochondria; Mitochondria, Heart - drug effects; Myocardium - enzymology; Oxidation-Reduction; Pharmacology. Drug treatments; Succinate dehydrogenase; Succinate Dehydrogenase - metabolism; Toxicity: cardiovascular system; Ubiquinone - metabolism; Cytochrome Oxidase; Succinate dehydrogenase; Mitochondria; Intracellular calcium; Cardiomyopathy; Coenzyme Q 10; Doxorubicin; Histochemistry; Antineoplastic agent; Heart; Toxicity; Rodentia; Vertebrata; Antibiotic; Mammalia; Mouse; Animal; Heart disease; Anthracyclins
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1016/0022-2828(83)90330-9

Histochemical alterations of acute and chronic doxorubicin (DOX) cardiotoxicity in the mouse were assessed by the localization of succinate dehydrogenase (SDH), coenzyme Q 10 (CoQ), cytochrome oxidase (COX), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), reduced glutathione (GSH), and intracellular calcium. Isolated myocytes intensely stained for calcium were found at 72 and 120 h under the acute protocol; altered staining patterns of SDH, CoQ, and COX, were evident at 120 h. Chronically, two patterns of intracellular calcium staining were evident: (1) intensely stained myocytes as found in the acute protocol; and (2) multiple discrete intracellular deposits suggestive of mitochondrial localization. Altered staining patterns of SDH, CoQ, COX, CPK, and LDH under the chronic protocol were only seen after abnormal staining was evident in trichrome stained sections. The presence of characteristic vacuolated myocardial cells in both acute and chronic protocols was confirmed by one micron epon-embedded toluidine blue stained sections and electron microscopy. These histochemical findings suggest that DOX alters the functional integrity of mitochondrial respiratory chain enzymes in the myocardial cell.