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

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.

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