Changes in lysosomal morphology and enzyme activities during the development of adriamycin-induced cardiomyopathy.
Morphologic and enzymic changes in heart lysosomes were studied following a chronic treatment of animals with a cumulative dose of 15 mg/kg of adriamycin. Myocardial cell damage due to adriamycin included lysosomal changes, sarcotubular swelling, vacuolization and myofibrillar drop-out. These structural changes were more pronounced in the 6-week treated group as opposed to the 3-week treated group. The number of lysosomes per unit area increased from a control value of 3.6 +/- 1.7 to 17.8 +/- 4.0 in the 3-week treated group and 35.9 +/- 9.2 in the 6-week treated groups, respectively. The scatter in the size distribution of lysosomes was much wider in treated animals. Lysosomal hydrolases in the 3-week and 6-week adriamycin-treated group changed as follows: N acetyl beta-glucosaminidase activity fell in the homogenate (H) and nonsedimentable (NS) and rose in the serum (Ser) fractions; a drop in alpha-mannosidase was seen in the sedimentable (S) and Ser fractions; an increase in beta-galactosidase was noted in the H, S and Ser fractions; acid phosphatase was increased in H, S, NS and Ser fractions. Lanthanum staining, used as a cytochemical probe for normal membrane permeability, revealed intracytoplasmic localization of the tracer only in the 6-week group. Malondialdehyde content was increased significantly in the 3-week and 6-weed treated groups. These results show lysosomal changes in adriamycin-treated hearts which precede as well as accompany nonspecific permeability changes in the sarcolemma.(ABSTRACT TRUNCATED AT 250 WORDS)
D000118:Acetylglucosaminidase / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D004317:Doxorubicin / Q000633:toxicity*; D008247:Lysosomes / Q000201:enzymology* / Q000648:ultrastructure; D008297:Male; D008361:Mannosidases / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D011919:Rats, Inbred Strains; D001616:beta-Galactosidase / Q000378:metabolism
D004317:Doxorubicin; D000135:Acid Phosphatase; D008361:Mannosidases; D001616:beta-Galactosidase; D000118:Acetylglucosaminidase