Reduced lipid peroxidation in dilated hearts of cardiomyopathic turkeys.
Adverse pulmonary reactions to some nitrofuran antibiotics are thought, in part, to involve production of reactive oxygen radicals. Furazolidone, a nitrofuran antibiotic, causes a dilated cardiomyopathy in domestic turkeys. The mechanism of this drug induced cardiomyopathy is unknown. We investigated the possible role of free radical injury in this heart failure model. Left ventricular lipid peroxidation capacity, assessed by two methods (the thiobarbituric acid reactive substances and lipid hydroperoxides assays respectively), was investigated in five 5-8 week old cardiomyopathic turkeys with severe cardiac dilatation, left ventricular dysfunction and systemic hypotension, and in five control birds. Superoxide dismutase activity, total and manganese, was also measured in the crude left ventricular homogenates. Both lipid peroxidation products were reduced in the myopathic hearts: thiobarbituric acid reactive substances (malondialdehyde) 70(SEM 4) v 86(3) nmol.100 mg protein-1 in controls, p less than 0.02; and lipid hydroperoxides 29(7) v 74(14) nmol.100 mg protein-1, p less than 0.02. Total superoxide dismutase activity was similar in cardiomyopathic and control hearts: 670(26) v 657(105) nitrite units.100 mg protein-1. Although total superoxide dismutase activity was unchanged, we found decreased manganese superoxide dismutase in the dilated hearts compared with controls (54% v 84% of total activity, p less than 0.02). In separate in vitro experiments furazolidone (2-10 mg.g wet weight-1) did not increase malondialdehyde production in turkey (or rat) left ventricular homogenates. These results indicate that cardiomyopathy induced by furazolidone is associated with decreased myocardial lipid peroxidation. Although as yet unexplained, the decrease may be due to a diminished amount of heart lipid susceptible to peroxidation accompanying the process of cardiac hypertrophy and dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)
Lax
D
D
Department of Pediatrics, University of Minnesota, Minneapolis.
Zhang
S L
SL
Li
Y
Y
Williams
L
L
Berry
J M
JM
Elsperger
J
J
Staley
N A
NA
Noren
G R
GR
Einzig
S
S
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000378:metabolism*; D005664:Furazolidone; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D011201:Poultry Diseases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism; D014422:Turkeys / Q000378:metabolism*
D008054:Lipid Peroxides; D008315:Malondialdehyde; D005664:Furazolidone; D013482:Superoxide Dismutase