title: Biochemical mechanisms of oxfenicine cardiotoxicity.
abstract: Oxfenicine (S-4-OH-phenyl-glycine) was proposed as a compound which would stimulate carbohydrate utilization in the heart and thus reduce oxygen requirement, especially in ischemic heart disease. Oral administration to rats for several weeks gave rise to an increase in heart, liver and kidney weights. The drug damaged mitochondrial metabolism, reducing oxygen consumption and uncoupling oxidative phosphorylation in all three organs. In heart mitochondria creatine phosphate kinase was inhibited and the creatine content of the mitochondria increased. Myocyte membrane functions (Ca uptake as well as Na/K-, Mg- and Ca-ATPases) were inhibited. In all three organs lipids (phospholipids and triglycerides) as well as free fatty acids showed a transient accumulation.
authors.affiliation: Swiss Federal Institute of Technology, Schwerzenbach, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Bachmann
authors.forename: E
authors.initials: E
authors.lastname: Weber
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D003402:Creatine Kinase / Q000037:antagonists & inhibitors; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D006321:Heart / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats
chemical_list: C023010:4-hydroxyphenylglycine; D003402:Creatine Kinase; D000251:Adenosine Triphosphatases; D003401:Creatine; D002118:Calcium; D005998:Glycine