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The effect of 4-hydroxy-2,2,6,6-tetramethyl-piperidine-1-oxyl(4-OH-TEMPO), a scavenger for free radicals, and 4-hydroxypyrazolo [3,4-d(pyrimidine)allopurinol], a xanthine oxidase inhibitor, on the hydrazine-induced changes of mitochondrial ultrastructure and those in the antioxidant system of the liver were investigated using rats as experimental animals. Animals were placed on a powdered diet containing 0.5% hydrazine for 7 d in the presence and absence of a combined treatment with 4-OH-TEMPO or allopurinol. Results obtained were as follows. 4-OH-TEMPO completely prevented the hydrazine-induced formation of megamitochondria in the liver, while it was partly prevented by allopurinol. The following changes observed in hydrazine-treated animals were improved almost completely by 4-OH-TEMPO:decreases in the body weight and liver weight; lowered rates of ADP-stimulated respiration and coupling efficiency of hepatic mitochondria; remarkable elevation of the level of lipid peroxidation. Improving effects of allopurinol were incomplete. The present results suggest that free radicals may play a key role in the mechanism of the hydrazine-induced formation of megamitochondria and that a part of free radicals generated during the hydrazine intoxication is ascribed to the degradation of purine nucleotides via xanthine oxidase. A general mechanism of the megamitochondria formation induced in various pathological conditions besides the case of hydrazine are discussed.
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
January 1997,
Molecular aspects of medicine,
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
February 1999,
Free radical biology & medicine,
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
January 1995,
Toxicologic pathology,
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
June 1994,
Experimental and molecular pathology,
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
February 1987,
Toxicology and applied pharmacology,
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
March 1975,
Acta pathologica japonica,
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
January 1975,
Acta pathologica japonica,
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
March 1978,
Acta pathologica japonica,
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
March 1978,
Acta pathologica japonica,
T Matsuhashi, and
X Liu, and
M Karbowski, and
M Wozniak, and
J Antosiewicz, and
T Wakabayashi
April 1960,
Proceedings of the National Academy of Sciences of the United States of America,
