Anti-hypotensive drug induced cardiotoxicity: an in vitro study. 2018

Aditi Jain, and Vibha Rani
Department of Biotechnology, Jaypee Institute of Information Technology, A-10, Sector-62, Noida, Uttar Pradesh, 210307, India.

Cardiotoxic side effects of broad range of drugs have emerged as an important cause of developing cardiovascular complications, as patients recover from one disease but develop another. Both cardiovascular and non-cardiovascular drugs may lead to the toxicity in the heart. Many drugs were initially not screened for cardiotoxicity, which is now an essential concern for drug discovery. Levophed is used for treating hypotension in critical care patients. Being a neurotransmitter, its concentration increases significantly in stress conditions and administration of this drug to patients' results in developing acute as well as persistent cardiac complications. Therefore, understanding its concentration-mediated effects and identifying the toxic concentration will serve as a platform to develop interventions to prevent adverse drug effects. In the present study, concentration and time-dependent effects of Levophed in H9C2 cardiomyoblasts were studied in detail by various cytotoxicity assays. Norepinephrine as a Levophed substitute was used and apoptotic cellular death was characterized by Annexin V and TUNEL DNA fragmentation assays. Morphological alterations, growth inhibition, and cellular death were also studied in detail. We observed that Levophed induces concentration-mediated deleterious effects in cardiomyoblasts. In-depth analysis of these effects will help in designing strategies in near future to combat and reduce this drug-induced cardiac toxicity.

UI MeSH Term Description Entries
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
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
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
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
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
D053938 DNA Fragmentation Splitting the DNA into shorter pieces by endonucleolytic DNA CLEAVAGE at multiple sites. It includes the internucleosomal DNA fragmentation, which along with chromatin condensation, are considered to be the hallmarks of APOPTOSIS. DNA Degradation, Apoptotic,Apoptotic DNA Degradation,Fragmentation, DNA
D032386 Myoblasts, Cardiac Precursor cells destined to differentiate into cardiac myocytes (MYOCYTES, CARDIAC). Cardiac Myoblast,Cardiac Myoblasts,Myoblast, Cardiac
D066126 Cardiotoxicity Damage to the HEART or its function secondary to exposure to toxic substances such as drugs used in CHEMOTHERAPY; IMMUNOTHERAPY; or RADIATION. Cardiac Toxicity,Cardiac Toxicities,Cardiotoxicities,Toxicity, Cardiac

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