Antimuscarinic action of doxorubicin does not involve free-radical formation in isolated guinea pig hearts. 2010

Takushi Sasaki, and Shunji Ueno, and Yukio Hara, and Tsuyoshi Uchide, and Kyosuke Temma
Laboratory of Toxicology, School of Veterinary Medicine, Kitasato University, 35-1 Higashi 23-bancho, Towada-shi, Aomori 034-8628, Japan.

It has been proposed that the cardiotoxicity of anthracycline anticancer drugs involves free-radical formation. One early manifestation of toxicity appears to be caused by the antimuscarinic actions of these drugs. Accordingly, we examined whether the antimuscarinic action of one of these drugs, doxorubicin, is altered by antioxidants. In electrically stimulated left atrial muscle preparations obtained from guinea pig hearts, doxorubicin significantly increased the tissue concentration of thiobarbituric acid-reactive substance indicating increased lipid peroxidation. This effect of doxorubicin was significantly suppressed by the antioxidants alpha-tocopherol, dexrazoxane, and epigallocatechin gallate. Carbachol produced a concentration-dependent negative inotropic effect in our atrial preparations. Doxorubicin caused a seemingly parallel rightward shift of the concentration-response curve for carbachol. Neither alpha-tocopherol, dexrazoxane, nor epigallocatechin gallate reversed this effect of doxorubicin. The results indicate that in extirpated heart tissue, doxorubicin causes lipid peroxidation through the formation of free radicals. However, this effect of doxorubicin is unrelated to its antimuscarinic action.

UI MeSH Term Description Entries
D008297 Male Males
D009206 Myocardium The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow. Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004317 Doxorubicin Antineoplastic antibiotic obtained from Streptomyces peucetius. It is a hydroxy derivative of DAUNORUBICIN. Adriamycin,Adriablastin,Adriablastine,Adriblastin,Adriblastina,Adriblastine,Adrimedac,DOXO-cell,Doxolem,Doxorubicin Hexal,Doxorubicin Hydrochloride,Doxorubicin NC,Doxorubicina Ferrer Farm,Doxorubicina Funk,Doxorubicina Tedec,Doxorubicine Baxter,Doxotec,Farmiblastina,Myocet,Onkodox,Ribodoxo,Rubex,Urokit Doxo-cell,DOXO cell,Hydrochloride, Doxorubicin,Urokit Doxo cell
D005609 Free Radicals Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. Free radicals include reactive oxygen and nitrogen species (RONS). They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. Free Radical
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D018727 Muscarinic Antagonists Drugs that bind to but do not activate MUSCARINIC RECEPTORS, thereby blocking the actions of endogenous ACETYLCHOLINE or exogenous agonists. Muscarinic antagonists have widespread effects including actions on the iris and ciliary muscle of the eye, the heart and blood vessels, secretions of the respiratory tract, GI system, and salivary glands, GI motility, urinary bladder tone, and the central nervous system. Antimuscarinic,Antimuscarinic Agent,Antimuscarinic Agents,Cholinergic Muscarinic Antagonist,Muscarinic Antagonist,Antimuscarinics,Cholinergic Muscarinic Antagonists,Agent, Antimuscarinic,Agents, Antimuscarinic,Antagonist, Cholinergic Muscarinic,Antagonist, Muscarinic,Antagonists, Cholinergic Muscarinic,Antagonists, Muscarinic,Muscarinic Antagonist, Cholinergic,Muscarinic Antagonists, Cholinergic

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