Journal of Microscopy, Vol. 00, Issue 0 2016, pp. 1–13 doi: 10.1111/jmi.12492 Received 3 May 2016; accepted 18 September 2016 Cardioprotective potential of curcumin against norepinephrine-induced cell death: a microscopic study C. MANGHANI, A. GUPTA, V. TRIPATHI & V. RANI Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Uttar Pradesh, India Key words. Apoptosis, cardiomyocytes, cardioprotection, cell death, curcumin, microscopic techniques, stress. Summary Cardiomyopathy and associated heart failure continues to be one of the most severe complications that threaten a large population. Curcumin, one of the three curcuminoids of the spice turmeric, is very well known for a multitude of health benefits and functions. Norepinephrine (NE), a catecholamine and also a stress hormone may cause the cardiomyocytes to develop increased sensitivity to death with its increasing con- centrations. In this study, we investigated the cardioprotective effect of curcumin in NE-induced cardiac apoptosis using sev- eral fluorescent and nonfluorescent microscopic techniques like DAPI, PI, Giemsa, PicroSirius and TUNEL. The aim of the study was to assess the effect of curcumin in preventing the occurrence of features underlying apoptosis such as nuclear disruption, chromatin condensation, DNA fragmentation and alterations in mitochondrial membrane permeability. Our re- sults show that curcumin protects the cardiomyocytes against apoptosis significantly and also helps them to revert to their normal physiological state. Hence, we propose that curcumin has the potential to act as a therapeutic agent for the atten- uation of NE-induced cardiac cell death and modulation of apoptosis in H9c2 cardiomyocytes. Introduction Hypertrophy refers to the increase in volume and size of an organ or tissue due to the enlargement of its component cells. Cardiac hypertrophy is one of the main diseases of the my- ocardium in which a portion of the myocardium thickens mak- ing it difficult for the heart to pump blood. If the hemodynamic load is not relieved, the hypertrophied heart ultimately dilates and fails resulting in a phenomenon termed ‘decompensation’ (Vanempel, 2004). This leads to the transition of the cells from hypertrophied to apoptotic stage (Jain et al., 2015). Correspondence to: Department of Biotechnology, Jaypee Institute of Infor- mation Technology, A-10, Sector-62, Noida 210307, Uttar Pradesh, India. Tel: + (91)-120-2594210; fax: + (91)-120-2400986; e-mail: vibha.rani@jiit.ac.in Circulating catecholamines closely correlate with the sever- ity and poor prognosis in heart failure and are thus considered to play a critical role in the development of cardiovascular dis- eases. Excessive release of catecholamines induces myocardial hypertrophy, myocyte damage and contractile dysfunction (Communal et al., 1998). Oxidative stress due to increased generation of reactive oxygen species (ROS) plays a pivotal role in the catecholamine-induced cardiotoxicity. NE, also called as noradrenaline, is a catecholamine secreted as a hor- mone through the medulla of adrenal glands and through the end of sympathetic nerve fibres. Prolonged exposure to NE causes heart failure, which is marked by apoptosis of cardiomy- ocytes. NE is known to exert its effect on the heart by activat- ing ß-adrenergic receptors and it mediates apoptosis through a tumor necrosis factor (TNF)-caspase mediated pathway (Communal et al., 1998; Fu et al., 2004). There are multiple cellular events that characterise the onset and induction of apoptosis. An in-depth study of these charac- teristics may provide insights into approaches for preventing heart failure by curbing apoptosis. Curcumin, a well-known phytoceutical and one of the main curcuminoids of turmeric, is well known for its beneficial effects in varied physiological con- ditions (Aggarwal & Harikumar, 2009). The cardio protective potential of curcumin has been investigated and established in our studies conducted earlier (Kohli et al., 2013; Ahuja et al., 2011) and hence it can be inferred that curcumin may be used to prevent cardiac stress. There are several proposed mechanisms by which curcumin exerts its cardioprotective action, one of them being inhibiting the activity of TNF, a lo- cal inflammatory cytokine whose over expression is said to contribute towards heart failure. Since curcumin is able to block and suppress the activity of TNF, whose β adrenergic receptor is activated by NE, we hypothesize that it can serve as a potential therapeutic agent to reverse the effects of NE in failing heart. Being inexpensive, safe and natural curcumin has several advantages over the existing TNF blockers such as Thalidomide (Immunoprin), Golimumab (Simponi) and Etan- ercept (Enbrel), which are known to cause a variety of side effects (Chattopadhyay et al., 2004). C  2016 The Authors Journal of Microscopy C  2016 Royal Microscopical Society