The induction of mitochondrial myopathy in the rat by feeding beta-guanidinopropionic acid and the reversibility of the induced mitochondrial lesions: a biochemical and ultrastructural investigation.
The long-lasting depletions of creatine phosphate induced by feeding rats with a beta-guanidinopropionic acid (GPA)-supplemented diet induces specific mitochondrial alterations in skeletal muscles very similar to those observed in human mitochondrial myopathies. The slow-twitch soleus muscle appears to be affected primarily, while the fast-twitch extensor digitorum longus is affected less severely and only after a longer period of treatment (6 months). Changes in the enzyme activities of glucose metabolism appear to be secondary and differ between the two muscles. Withdrawal of GPA from the diet after 2 months of treatment shows that both mitochondrial alterations and biochemical modification are reversible.
De Tata
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V
Istituto di Patologia Generale, Università degli Studi di Pisa, Italy.
Cavallini
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G
Pollera
M
M
Gori
Z
Z
Bergamini
E
E
D000818:Animals; D004032:Diet; D006146:Guanidines / Q000633:toxicity*; D008297:Male; D008854:Microscopy, Electron; D008931:Mitochondria, Muscle / Q000187:drug effects* / Q000648:ultrastructure; D017240:Mitochondrial Myopathies / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology; D009132:Muscles / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D011422:Propionates / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015430:Weight Gain / Q000187:drug effects
D006146:Guanidines; D011422:Propionates; C005775:guanidinopropionic acid