Insight into the role of DL-alpha-lipoic acid against cyclophosphamide induced alterations in calcium sensitivity of cardiac myofilaments. 2006

Y Mythili, and P T Sudharsan, and P Varalakshmi
Department of Medical Biochemistry, Dr. ALM. Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, India.

Cyclophosphamide (CP), a potent antitumor drug, is known to cause severe cardiotoxicity. The present study is aimed at evaluating the role of DL-alpha-Lipoic acid (LA) on the calcium responsiveness of cardiac myofilaments isolated from CP treated rats. Adult male Wistar rats were divided into four treatment groups. Two groups received single intraperitoneal injection of CP (200 mg/kg b.wt.) to induce cardiotoxicity, one of these groups received LA treatment (25 mg/kg b.wt. for 10 days). A vehicle treated control group and a LA drug control were also included. Cardiotoxicity was evident from increased levels of cardiac Troponin I in serum of CP treated rats. The pCa-actomyosin ATPase relationship of myofilaments demonstrated a rightward shift indicating diminished responsiveness in CP treated rats. The hill coefficient was reduced and the myofibrillar myosin Ca(2+)-ATPase and K(+)-(EDTA) activities were also significantly (P < 0.05) reduced. Ultrastructural observations were also in agreement with the above abnormal changes, wherein loss of myofilaments occurred. LA effectively normalized these abnormalities and restored the cardiac function in CP administered rats.

UI MeSH Term Description Entries
D008063 Thioctic Acid An octanoic acid bridged with two sulfurs so that it is sometimes also called a pentanoic acid in some naming schemes. It is biosynthesized by cleavage of LINOLEIC ACID and is a coenzyme of oxoglutarate dehydrogenase (KETOGLUTARATE DEHYDROGENASE COMPLEX). It is used in DIETARY SUPPLEMENTS. Lipoic Acid,Alpha-Lipogamma,Alpha-Lipon Stada,Alpha-Liponsaure Sofotec,Alpha-Lippon AL,Alphaflam,Azulipont,Fenint,Juthiac,Liponsaure-ratiopharm,MTW-Alphaliponsaure,Neurium,Pleomix-Alpha,Pleomix-Alpha N,Thioctacid,Thioctacide T,Thiogamma Injekt,Thiogamma oral,Tromlipon,Verla-Lipon,alpha-Lipoic Acid,alpha-Liponaure Heumann,alpha-Liponsaure von ct,alpha-Vibolex,biomo-lipon,duralipon,espa-lipon,Acid, alpha-Lipoic,Alpha Lipogamma,Alpha Lipon Stada,Alpha Liponsaure Sofotec,Alpha Lippon AL,AlphaLipogamma,AlphaLipon Stada,AlphaLiponsaure Sofotec,AlphaLippon AL,Injekt, Thiogamma,Liponsaure ratiopharm,Liponsaureratiopharm,MTW Alphaliponsaure,MTWAlphaliponsaure,Pleomix Alpha,Pleomix Alpha N,PleomixAlpha,PleomixAlpha N,Verla Lipon,VerlaLipon,alpha Lipoic Acid,alpha Liponaure Heumann,alpha Liponsaure von ct,alpha Vibolex,alphaLiponaure Heumann,alphaLiponsaure von ct,alphaVibolex,biomo lipon,biomolipon,espa lipon,espalipon
D008297 Male Males
D008841 Actin Cytoskeleton Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments. Actin Filaments,Microfilaments,Actin Microfilaments,Actin Cytoskeletons,Actin Filament,Actin Microfilament,Cytoskeleton, Actin,Cytoskeletons, Actin,Filament, Actin,Filaments, Actin,Microfilament,Microfilament, Actin,Microfilaments, Actin
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
D009218 Myosins A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain. Myosin ATPase,ATPase, Actin-Activated,ATPase, Actomyosin,ATPase, Myosin,Actin-Activated ATPase,Actomyosin ATPase,Actomyosin Adenosinetriphosphatase,Adenosine Triphosphatase, Myosin,Adenosinetriphosphatase, Actomyosin,Adenosinetriphosphatase, Myosin,Myosin,Myosin Adenosinetriphosphatase,ATPase, Actin Activated,Actin Activated ATPase,Myosin Adenosine Triphosphatase
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003520 Cyclophosphamide Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer. (+,-)-2-(bis(2-Chloroethyl)amino)tetrahydro-2H-1,3,2-oxazaphosphorine 2-Oxide Monohydrate,B-518,Cyclophosphamide Anhydrous,Cyclophosphamide Monohydrate,Cyclophosphamide, (R)-Isomer,Cyclophosphamide, (S)-Isomer,Cyclophosphane,Cytophosphan,Cytophosphane,Cytoxan,Endoxan,NSC-26271,Neosar,Procytox,Sendoxan,B 518,B518,NSC 26271,NSC26271
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
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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