Cardiotoxicity of Plants in Iran: a Review

Document Type : Review Articles


University of Shahrekord


In this review an attempt has been made to review the cardiotoxic effects of poisonous plants which are found in Iran. Among various plant species growing in different regions of Iran, a large number of plants contain chemical compounds which are toxic to animals and humans. Among those poisonous plants, cardiotoxic plants are important due to the acute nature of their toxicity and frequent lethal livestock and human intoxications. Cardiotoxic plants of Apocynaceae family, Nerium oleander, N. indicum and Thevetia peruviana contain cardiac glycosides including oleandrin, oleandroside and thevetin A-C. Plants of Taxaceae family, Taxus baccata and T. brevifolia contain taxine alkaloids, including taxine A and B. The toxic effects of cardiac glycosides are primarily attributed to inhibition of plasmalemmal Na+/ K+-ATPase which results into the accumulation of intracellular Ca2+ and, depending to its severity, inotropic or arrhythmic effects are seen. Taxine B, the prominent alkaloid in Taxus spp. block sodium and calcium channels preferentially in cardiac myocytes, thus causing conduction abnormalities. Various cardiac arrhythmias in acute cases of poisoning with aforementioned plants result in acute heart failure and death. Post mortem findings are non-diagnostic and toxicological analysis of gastrointestinal tract content or body fluids is used for detection of cardiac glycosides and taxines.


Ghahreman A, Attar F. Biodiversity of plant species in Iran. 2000; vol. 1. Tehran University publications.
Aslani MR. Poisonous plants of Iran and their effects on Animals. 2004; Ferdowsi University of Mashhad Press, Mashhad.
Aslani MR, Movassaghi AR, Najarnezhad V, Janati- Pirouz H, Heidaipour-Bami M. Acute oxalate intoxication associated to ingestion of Eshnan (Seidlitzia rosmarinus) in sheep. Tropical Animimal Health and Production 2011; 43, 1065-1068.
Aslani MR, Maleki M, Mohri M, Najjar-Nazhad V, Afshari E. Castor bean (Ricinus communis) toxicosis in a sheep flock. Toxicon 2007; 49: 400-406.
Afshari A, Majdzadeh R, Balali-Moog M. Patterns of acute poisoning in Mashhad, Iran 1993-2000. Journal Toxicology. Clinical Toxicolology 2004; 42: 965-975.
Amini M, Khosrojerdi H, Afshari R. Acute Datura Stramonium poisoning in east of Iran-a case series. Avicenna Journal of Phytomedicine 2012; 2: 86-89.
Bandara V, Weinstein SA, White J, Eddleston M. A review of the natural history, toxinology, diagnosis and clinical management of Nerium oleander(common oleander) and Thevetiaperuviana(yellow oleander) poisoning. Toxicon 2010; 56: 273-281.
Aslani MR, Binas N, Shaterzadeh H. Thevetia peruviana, a poisonous plant in Iran. 6th congress of Iranian Veterinary Practitioners 2008; 28-30 July, Tabriz.
Portis E, Comino C, Lenzi A, Lombardi P, Tesi R, Lanteri S. Amplified fragment length polymorphism fro variety identification and genetic diversity assessment in oleander (Nerium oleander L.). Euphytica 2004; 136: 125-137.
Nesy EA, Lizzy M. HPLC profiling of cardiac glycosides if Thevetia peruviana leaf extracts of three morphovariant plants grown in Kerala, India. International Journal of Pharmacology and Pharmacological Sciences 2015; 7: 191-195.
Camplesi AC, Bellodi C, Socha JJM, Hatayde MR, Sobreira MFR, Araujo GSM, Araujo CFM. Dogs poisoned with Nerium oleander fresh leaves: clinical and electrocardiographic findings. Ciência Rural, Santa Maria 2017; 47: 06. E2016o970.
Miller M, Adams HR. Digitals, Positive Inotropes and Vasodilators. In: Veterinary Pharmacology and Therapeutics. 2009; 9thEdn, Ed By RiviereJE.,Papich MG., Adams HR., Willey-Blackwell.
Baeceloux DG. Medical Toxicology and Natural Substances: Foods, Fungi, Medicinal Herbs, Plants, and Venomous Animals. 2008; Wiley, New Jersy,
KohlsS, Scholz-Bottcher BM, Teske J, Zark P, Rullkotter J. Isolation and quantification of six cardiac glycosides from seeds of Thevetia peruviana provide a basis for toxicological survey. Indian Journal of Chemistry 2015; 54B: 1502-1510.
Kumar A, De T., Mishra A, Mishra AK. Oleandrin: A cardiac glycosides with potent cytotoxicity. Pharmacognosy Reviews 2013; 7: 131-139.
Siddiqui BS, Sultana R, Begum S, Zia A, Suri A. Cardenolides from the methanolic extract of Nerium oleander leaves possessing central nervous system depressant activity in mice. Journal of Natural Production 1997; 60, 540-544.
Sundaragiri S, Tandur S. Electrocardiographic Profile of Cardiotoxic Plants and Animals. International Journal of Medical Research and Health Sciences, 2016; 11:719-725.
Nadji S, Abdaoui A, Ouerdane H, Azzouz M, Abtroun R, Reggab M, Alamir B. Determination of oleandrin levels by HPLC-DAD in vegetal material collected throughout Algeria and the study of some influencing factors. Research Journal of Phytochemistry 2017; 26: 74-84.
Praveen US, Gowtham MD, Yogaraje-Gowda CV, Nayak VG, Mohan BM. Detection of residues of cardenolides of Nerium oleander by high-performance thin-layer chromatography in autopsy samples. International Journal of Medical Toxicology and Forensic Medicine 2012; 2:135-142.
Langford SD, Boor PJ. Oleander toxicity: an examination of human and animal toxic exposures. Toxicology 1996; 109: 1-13.
Casteel SW, Schaffer JW. Collapse and sudden death. In: Large Animal Internal Medicine, 5th Edn, Ed By Smith B,
Rezakhani A, Maham M. Cardiac manifestation of oleander poisoning in cattle and donkeys. In: Colegate, SM and Darling, PR (Eds.), Plant associated toxins agricultural, phytochemical and ecological aspects. (1st. Edn.), London, CAB International 1994; PP: 538-540.
Aslani MR. Study on the mechanism of V285 treatment of experimental oleander poisoning in calves. PhD thesis 1995, School of Veterinary Medicine, University of Shiraz, Iran.
Aslani MR, Movassaghi AR, Mohri M, Abbasian A, Zaerpour M. Clinical and pathological aspects of experimental oleander (Nerium oleander) toxicosis in sheep. Veterinary Research Communication 2004; 28: 609-6016.
Aslani MR, Movassaghi AR, Janati-Pirouz H., Karazma M. Experimental oleander (Nerium oleander) poisoning in goats: a clinical and pathological study. Irish Journal of Veterinary Research 2007; 8: 58-63.
Senthilkumaran S, Meenakshisundaram R, Michaels AD, Thirumalaikolundusubramanian P. Electrocardiographic changes during inhalational oleander toxicity. Journal of Electrocardiology 2011; 44: 470–472.
Nelson LS, Shih RD, Balick MJ. Handbook of poisonous and Injurious Plants. 2007, 2nd Edn, Springer, NewYork.
Senthilkumaran S, Saravanakumar S, Thirumalaikolundusubramanian P. Cutaneous absorption of oleander: Fact or fiction. Journal of Emergencies, Trauma and Shock. 2009; 2: 43–45.
Bijl PVD. Cardiotoxicity of plants in South Africa. Cardiovascular Journal of Africa 2012; 23: 476–477.
Galey DF. Cardiac glycosides. In: Plumlee KH., Veterinary Clinical Toxicology. 2007 Elsevier, St Louis.
Peiris-John RJ, Wickremasinghe AR. Efficacy of activated charcoal in yellow oleander poisoning. Ceylon Medical Journal 2008; 53: 33-35.
Ni D, Madden TL, Johansen M, Felix E, Ho DH, Newman RA. Murine pharmacokinetics and metabolism of oleandrin, a cytotoxic component of Nerium oleander. Journal of Experimental Therapeutic Oncolology 2002; 2:278-85.
Marcus FL, Huang SK. Digitalis. In: The Heart, Arteries and Veins, Ed by Hurst JW, Schlant RC, 1990; McGrew-Hill Information Service Company, New York.
Rezakhani A, Maham M. Oleander poisoning in cattle of the Fars Province, Iran. Veterinary and Human Toxicology 1992; 34: 549.
Aslani MR, Rezakhani A. A case report of oleander (Nerium oleander) intoxication in Cattle. International Journal of Tropical Agriculture 2000; 18: 185-187.
Rajapakse S. Management of yellow oleander poisoning. Clinical Toxicology 2009; 47: 206-212.
Mannineh V, Nyberg L. Interaction between cardiac glycosides and other substances in the body. In: Cardiac Glycosides, part II: Pharmacokinetics and Clinical pharmacology, Ed by Greef K 1981, Springer, New York.
Roberts AM, Gallapatthy G, Dunuwille A, Chan BS. Pharmacological treatment of cardiac glycoside poisoning. British Journal of Clinical Pharmacology 2016; 81: 488–495
Miller MW, Adams HR. Digitalis, Positive Inotropes and Vasodilators. In: Veterinary Pharmacology and Therapeutics, 9th Edn, Ed by Riviere JE, Papich MG, 2009; Wiley-Blackwell.
Konstantinou DM, Karvounis H, Giannakoulas G. Digoxin in Heart Failure with a Reduced Ejection Fraction: A Risk Factor or a Risk Marker? Cardiology 2016; 134:311-319.
Lelie`vre LG, Lechat Ph. Mechanisms, manifestations, and management of digoxin toxicity. Heart and Metabism 2007; 35: 9–11.
Wasserstrom JA, Aistrup GL. Digitalis: new actions for an old drug. American Journal Physiology- Heart and Circulatory Physiology 2005; 289: H1781–H1793.
Ho HT, Liu B, Snyder JS, Lou Q, Brundage EA, Velez-Cortes F, Wang H, Ziolo MT, Anderson ME, Sen CK, Wehrens XHT, Fedorov VV, Biesiadecki BJ, Hund TJ, Gyorke S. Ryanodine receptor phosphorylation by oxidized CaMKII contributes to the cardiotoxic effects of cardiac glycosides. Cardiovascular Research 2014; 101: 165–174.
Kanji S, McLean RD. Cardiac glycoside toxicity: More than 200 years and counting. Critical Care Clinics 2012; 28: 527–535.
45. Renier AC, Cass PhH., Magdesian KG., Madigan JE., Aleman M., Pusterla N. Oleander toxicosis in equids: 30 cases (1995–2010). Journal of American Veterinary Medical Association 2013; 242: 540-549.
Butler J, Khan S, Scarzella G. Fatal oleander toxicosis in two miniature horses. Journal of American Animal Hospital Association 2016; 42: 398-402.
Page C, Murtaugh RJ. Hypoglycemia Associated With Oleander Toxicity in a Dog. Journal of Medical Toxicology 2015; 11:141–143.
Vashishta MS, Singh RP. Camel Disease in India. 1977, Scientific Book Agency, Calcutta.
Kosikowski TA, Magdesian G, Puschner B. Oleander intoxication in New World Camelids: 12 cases (1995-2006). Journal of American Veterinary Medical Association 2009; 235: 305-310.
Galey FD, Holstege DM, Plumlee KH, Tor E, Johnson B, Anderson ML, Blanchard PC, Brown F. Diagnosis of oleander poisoning in livestock. Journal of Veterinary Diagnosis Investigation 1996; 8: 358-364.
Tor ER, Filigenzi MS, Puschner B. Determination of oleandrin in tissues and biological fluids by liquid chromatography-electrospray tandem mass spectrometry. Journal of Agriculture and Food Chemistry 2005; 53: 4322-5.
Constable PD, Hinchkliff KW, Done SH, Grunberg W. Veterinary Medicine, A Textbook of the Diseases of Cattle, Horses, Sheep, Pigs and Goats. 11th Edn, 2017; Elsevier, St Louis.
Yazdiani D, Shahnazi S, Rezazadeh SH, Pir Ali Hamedani M. A review on T. baccata. Journal of Medicinal Plants 2005; 4: 1-8.
Janfaza S, Pourmajidiyan MR, Moradi M. Study of the ecological status of Iranian yew herbal towards its revival in Iran and the word in recent years. Annals of Biological Research 2014; 5: 68-71.
Thomas PA, Polwart A. Biological flora of the British Isles: Taxus baccata. Journal of Ecolology 2003; 91: 489-524.
Labossiere AW, Thompson DF. A review of the clinical toxicology of yew poisoning. Annals of Pharmacology 2018; 1-9, DOI: 10.1177/1060028017754225 .
Wilson CR, Hooser SB. Toxicity of yew (Taxus spp) alkaloids. In: Gupta RC, Veterinary Toxicology; Basic and Clinical Principles. 2012; 2nd edition, Academic press.
Tiwary AK, Puschner B, Kinde H, Tor ER. (2005) Diagnosis of Taxus (Yew) poisoning in a horse. Journal of Veterinary Diagnostic Investigation 17; 252-255.
Itokawa H, Lee KH. Taxus: The Genus Taxus. 2003; Tylor & Francis, London; pp 153-156.
Sufness M. Taxol: Science and Applications. 1995; CRC Press, Boca Raton, pp 7/8-311/312.
Casteel SW. Taxine alkaloids. In: Plumlee KH, Veterinary Clinical Toxicology. 2007; Elsevier, St Louis.
Sula MJM, Morgan S, Baily KL, Schumpert M, Njaa BL. Characterization of cardiac lesions in calves after ingestion of Japanese yew (Taxus cuspidate). Journal of Veterinary Diagnostic Investigation 2013; 25: 522-526.
Persico A, Bacis G, Uberti F, Panzeri C, Lorenzo CD, Moro E, Restani P. Identification of taxine derivatives in biological fluids from a patient after attempted suicide by ingestion of yew (Taxus baccata) leaves. Journal of Analytical Toxicology 2011; 35: 238-241.
Valis M, Koci J, Tucek D, Lutonsky T, Kopova J, Barton P, Vysata O, Krajickova D, Korabekny J, Masopust J, Klzo L. Common yew intoxication: a case report. Journal of Medical Case Report 2015; 8: 1/4.
Holstege CP, Eldridge DL, Rowden AK. ECG manifestations: the poisoned patient. Emergency Medicine Clinics of North America 2006; 24: 159-177.
Andersen KB. Future perspectives of the role of taxines derived from the yew (Taxus baccata) in research and therapy. Journal of Pre-Clinical and Clinical Research 2009; 3: 1-4.
Aslani MR, Taghavi-Rezavi-Zadeh AR, Mohri M, Movassaghi AR, Nabipour A, Rezakhani A, Yaghoobi-Faz S, Andalib A, Ahmadi F. Clinical and pathological study on experimentally induced yew (Taxus baccata) poisoning in sheep. Iranian Journal of Veterinary Science and Technology 2011; 3: 11-22.
Evans KL, Cooke IR. Japanese yew poisoning in a dog. Journal of American Animal Hospital Association 1991; 27; 300-302.
Perju-Dumbrava D, Morar S, Chiroban O, Lechintan E, Cioca A. Suicidal poisoning by ingestion of Taxus Baccata leaves. Case report and literature review. Romanian Journal of Legal Medicine 2013; 21: 115-118.
Piskac O, Střibrnýb J, Rakocova H, Malý M, Cardiotoxicity of Yew. Cor et Vasa 2015; 57: 234-238.
Cerrato M, Calzolaria G, Tizzani P, Perinetto EA, Dellavalle A, Aluffi E. Bizarre and scary ECG in yew leaves poisoning: Report of successful treatment. Ann Noninvasive Electrocardiol. 2018;e12535.