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Effects of chronic torbafylline treatment on energy metabolism of ischemic skeletal muscle
Author(s) -
Comte Jane,
Gautheron Danièle C.,
Godinot Catherine,
OkyayuzBaklouti Ismahan
Publication year - 1990
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430200304
Subject(s) - medicine , endocrinology , skeletal muscle , creatine kinase , chemistry , xanthine oxidase , adenine nucleotide , creatine , malate dehydrogenase , mitochondrion , ischemia , oligomycin , atpase , saline , biochemistry , enzyme , nucleotide , gene
This study investigates the effects of chronic oral treatment with Torbafylline, a xanthine derivative, on the energy metabolism of chronically ischemic skeletal muscle of the rat. Blood flow to one hindlimb was reduced by unilateral femoral artery ligation. One group of animals received 5 ml/kg body weight saline while the other group received 25 mg/kg Torbafylline dissolved in the same volume of saline. Treatment was pursued for 5 weeks, 2 times a day, except during the weekends. In NaCI‐treated rats, ischemia leads to muscle atrophy as measured by a decrease in muscle weights and to a concomitant decrease in lactate dehydrogenase and creatine kinase activities, while adenine nucleotide contents remain unchanged. Chronic administration of Torbafyllin almost totally prevented these changes. In isolated mitochondria from ischemic and non‐ischemic muscles, treated or not with Torbafylline, no significant changes were measured in malate dehydrogenase, citrate synthase, creatine kinase, cytochrome oxidase and oligomycin‐sensitive ATPase. However, in mitochondria prepared from NaCI‐treated muscles with limited flow, an increase of substrate oxidation was observed after formation of endogenous ATP (final state 4 of oxidation). This increase can be interpreted as an indication of a deviation from the normal use of ATP, e.g., non‐efficient energy production. Torbafylline treatment prevented this apparent waste of energy.