1 |
Isoprenaline |
Synthetic catecholamine and β-adrenergic agonist |
• Hypoxia due to hyperactivity of myocardium. • Fall of pressure in coronary arteries, overload of calcium. • Removal of high energy phosphate as well as production of free radicle because of auto oxidation of catecholamine leading to membrane peroxidation. |
85 mg/kg |
Amran et al., 2015Amran AZ, Jantan I, Dianita R, Buang F. Protective effects of the standardized extract of Zingiber officinale on myocardium against isoproterenol-induced biochemical and histopathological alterations in rats. Pharm Biol. 2015;53(12):1795-802.
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2 |
Aluminium Chloride |
Salt of aluminium and chlorine |
• Oxidative stress • Disturbance in the intracellular redox framework. • Prooxidant properties of aluminium |
50 mg/kg |
Ghorbel et al., 2017Ghorbel I, Elwej A, Chaabane M, Jamoussi K, Zeghal N. Protective effect of selenium against aluminium chloride induced cardiotoxicity in rats. Pharm Biomed Res. 2017;3(2):19-25.
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3 |
Azithromycin |
Macrolides Antibiotics |
• Oxidative stress occurs due to a disruption in the antioxidant defense system • An increase in the generation/production of reactive oxygen species in the cases of ischemia-reperfusion. • The changes in the cardiac functions and the functions of ion channels, ionic pumps, ion exchangers, connexin-43 remodeling and inflammatory processes have been suggested to be associated with the oxidative stress |
15 mg/kg and 30 mg/kg |
Atli et al., 2015Atli O, Ilgin S, Altuntas H, Burukoglu D. Evaluation of azithromycin induced cardiotoxicity in rats. Int J Clin Exp Med. 2015;8(3):3681-90.
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4 |
Bupivacaine |
Long-acting local anaesthetic |
• Bupivacaine reduces the availability of fatty acids for β-oxidation in myocardial mitochondria by specific inhibition of the enzyme systems involved in the carnitine shuttle. • The resulting loss of energy substrate potentially could contribute to the cardiotoxicity observed clinically. • Conduction blockade by inhibiting Na channel and negative inotropy. |
6 µg/mL |
Křikava et al., 2010Křikava I, Jarkovský J, Štourač P, Nováková M, Ševčík P. The effects of lidocaine on bupivacaine-induced cardiotoxicity in the isolated rat heart. Physiol Res. 2010;59(Suppl 1):S65-9.
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5 |
Carbon tetrachloride |
Clear, colourless, volatile, heavy and nonflammable liquid |
• Production of free radicals which is a rate limiting process in cellular peroxidative damage, causing oxidative stress, which produces the major interrelated changes in cellular metabolism, thus increasing the level of calcium inside the cell. • Causes damage to the permeability and transport of ions through membrane and also destroy the cell by lipid peroxidation. |
1mL/kg |
Eshaghi et al., 2012Eshaghi M, Zare S, Banihabib N, Nejati V, Farokhi F, Mikaili P. Cardioprotective effect of cornus mas fruit extract against carbon tetrachloride induced-cardiotoxicity in albino rats. J Basic Appl Sci Res. 2012;2(11):11106-14.
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6 |
Chlorpyrifos |
Broad spectrum organophosphate insecticide |
• Chlorpyrifos has multiple effects on cells including generation of reactive oxygen species and induction of intracellular oxidative stress thereby disrupting normal cellular development and differentiation of cell. |
5.4 mg/kg |
Baş, Kalender, 2011Baş H, Kalender Y. Chlorpyrifos induced cardiotoxicity in rats and the protective role of quercetin and catechin. Gazi Univ J Sci. 2011;24(3):385-95.
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7 |
Cisplatin |
Organometallic chemotherapeutic drug |
• Cisplatin reacts with DNA, and causes intra and inter crosslinkage. The subsequent DNA produced starts apoptosis. • It induces oxidative stress |
7.5 mg/kg |
Oguzturk et al., 2016Oguzturk H, Ciftci O, Cetin A, Kaya K, Disli OM, Turtay MG. Beneficial effects of hesperidin following cis - diamminedichloroplatinum - induced damage in heart of rats. Niger J Clin Pract. 2016;19(1):99-103.
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8 |
Clozapine |
Antipsychotic drug |
• Possible IgE-mediated hypersensitivity reaction. • Hyper-catecholaminergic states. • An increased release of inflammatory cytokines. • An increase in ROS. |
10, 15, 25 mg/kg |
Abdel-Wahab, Metwally, 2014Abdel-Wahab BA, Metwally ME. Clozapine-induced cardiotoxicity in rats: Involvement of tumour necrosis factor alpha, NF-κβ and caspase-3. Toxicol Reports. 2014;1:1213-23.
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9 |
Cyclophosphamide |
Antineoplastic and immunosuppressant agent |
• Cyclophosphamide quickly disturbs the cellular respiration • It harms the internal mitochondrial layer of heart prompting the penetrability of calcium ion is mediated by oxidative stress. • Cyclophosphamide initiated cardiotoxicity has been involved in increasing the production of superoxide radicals and hydrogen peroxide. |
150 mg/kg |
Gado et al., 2013Gado AM, Nasser A, Adam I, Aldahmash BA. Cardiotoxicity induced by cyclophosphamide in rats: Protective effect of curcumin. J Res Environ Sci Toxicol. 2013;2(4):2315-5698.
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10 |
Doxorubicin |
Anthracycline category anti-cancer drug |
• Doxorubicin causes myocardial injury by means of the development of free oxygen radicals. • Oxidative injury to membrane lipids and other cellular component, injury to the microtubules, vacuolization, and sarcomere disturbance occurs in myoctes. |
1 mg/kg, 2.5 mg/kg |
Shahzadi et al., 2014Shahzadi A, Sonmez I, Allahverdi O, Onal B, Kandaz C, Ozyazgan SO, et al. Cardiac Troponin-I (cTnI) a biomarker of cardiac injuries induced by doxorubicin alone and in combination with ciprofloxacin, following acute and chronic dose protocol in sprague dawley rats. Int J Pharmacol. 2014;10(5):258-66.
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11 |
Gamma Radiation |
Very short wavelength electromagnetic radiation |
• Biological frameworks of the body to deliver free radicals or reactive oxygen species (ROS), which causes injury to different cellular segment including DNA, proteins and membrane lipids, prompting chronic cellular injury. |
10 Gy delivered at a dose rate of 0.46 Gy/min. |
Elkady, Mohamed, 2016Elkady AA, Mohamed ET. Possible role of withania somnifera against gamma radiation induced cardiotoxicity in male albino rats. Pak J Zool. 2016;48(2):539-45.
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12 |
Imatinib |
Tyrosine kinase inhibitor based anti-cancer drug. |
• Mitochondrial abnormalities and accumulation of membrane whorls. Autophagy. • Cell death in H9c2 cardiac muscle cell. • The cardiotoxic actions of Imb are thought to be mediated through suppression of fusion protein BCR-ABL activity. • Mitochondrial membrane potential and cell viability. |
10 to 50 mg/kg, 100 mg/kg |
Herman et al., 2011Herman EH, Knapton A, Rosen E, Thompson K, Rosenzweig B, Estis J, et al. A multifaceted evaluation of imatinib-induced cardiotoxicity in the rat. Toxicol Pathol. 2011;39(7):1091-106.
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13 |
Lead and Mercury |
Heavy metals |
• It is related to be enhanced ROS and oxidative stress in heart tissue, leading to biochemical alterations and heart tissue damage. |
Lead 45 mg/kg Mercury 0.02 mg/kg |
Kalender, 2016Kalender S. Effects of mercury chloride and lead nitrate induced cardiotoxicity in male rats. J Harran Univ Med Fac. 2016;13:136-43.
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14 |
Lithium |
Mood stabilizer metal, Antimanic |
• Li may directly or indirectly induce oxidative stress through the mitochondria via redox cycling, or promoting iron accumulation and oxidative/nitrative modifications of essential mitochondrial proteins. |
2, 5, or 100 mg/kg |
Mezni et al., 2017Mezni A, Aoua H, Khazri O, Limam F, Aouani E. Lithium induced oxidative damage and inflammation in the rat’s heart: Protective effect of grape seed and skin extract. Biomed Pharmacother. 2017;95:1103-11.
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15 |
Penconazole |
Systemic fungicide |
• It induced a state of oxidative stress in the heart of adult rats as proved by the increased lipid peroxidation, PCO formation, and the changed enzymatic and nonenzymatic antioxidant situation. • Its administration also resulted in inhibition of the cardiac AChE activity and altering the metabolism of lipid. • The toxic effects of PEN are basically mediated through free radical generation, leading to injury in various cardiomyocyte structure. |
67 mg/kg |
Chaâbane et al., 2016Chaâbane M, Tir M, Hamdi S, Boudawara O, Jamoussi K, Boudawara T, et al. Improvement of heart redox states contributes to the beneficial effects of selenium against penconazole-induced cardiotoxicity in adult rats. Biol Trace Elem Res. 2016;169(2):261-70.
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16 |
Tilmicosin |
Macrolide antibiotic |
• TMC causes positive chronotropic and negative inotropic cardiovascular dysfunction with increased heart rate and loss of ventricular function results in causing various degree of lipid peroxidation, inhibition in antioxidant enzymes activities and changes in serum biochemical parameters. |
75 mg/kg |
Ibrahim, Abdel-Daim, 2015Ibrahim A, Abdel-Daim M. Modulating effects of spirulina platensis against tilmicosin-induced cardiotoxic-ity in mice. Cell J. 2015;17(1):137-144.
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