Peganum harmala, is a plant of the family Nitrariaceae with small seeds, traditionally used to induce abortion and menstruation. It also has pharmacological properties such as lowering blood glucose, as well as analgesic, anti-cancer, antibacterial and antifungal effects. The current report presents a rare case of a middle-aged female referring to Clinical Toxicology Service with the history of drinking a glass of boiled Esfand seeds, in order to reduce blood sugar, and complaining of nausea, abdominal pain, general weakness, dizziness, and several vomiting episodes.

Ataee, Zahra

Dadpour, Bita

Najari, Dorsa

Najari, Fares

Rahimpour, Mehran

English

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119Case Report: Acute Poisoning With Peganum Harmala, Esfand: A Rare Case ReportZahra Ataee1 , Bita Dadpour2, Fares Najari3* , Mehran Rahimpour4, Dorsa Najari5 1. Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Department of Medical Toxicology, School of Medicine, Imam Reza Hospital, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Department of Forensic Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.4. School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.5. School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.* Corresponding Author: Fares Najari, MDAddress: Department of Forensic Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.Tel: +98 (912) 3195140E-mail: najari.hospital@sbmu.ac.irPeganum harmala, is a plant of the family Nitrariaceae with small seeds, traditionally used to induce abortion and menstruation. It also has pharmacological properties such as lowering blood glucose, as well as analgesic, anti-cancer, antibacterial and antifungal effects. The current report presents a rare case of a middle-aged female referring to Clinical Toxicology Service with the history of drinking a glass of boiled Esfand seeds, in order to reduce blood sugar, and complaining of nausea, abdominal pain, general weakness, dizziness, and several vomiting episodes. A B S T R A C TKeywords:Zygophyllaceae, Harmaline, Triterpenes, PoisoningCitation: Ataee Z, Dadpour B, Najari F, Rahimpour M, Najari D. Acute Poisoning With Peganum Harmala, Esfand: A Rare Case Report. International Journal of Medical Toxicology and Forensic Medicine. 2018; 8(3):119-121. https://doi.org/10.22037/ijmtfm.v8i3(Summer).22342 :  https://doi.org/10.22037/ijmtfm.v8i3(Summer).22342Use your device to scan and read the article onlineArticle info: Received: 28 Dec 2017First Revision: 20 Jan 2018Accepted: 17 May 2018Available Online: 01 Jul 2018Funding: See Page 121 Copyright: The Author(s)1. Introductionsfand or Peganum harmala is traditionally used in the Middle East countries such as Turkey, Syria, Pakistan, Afghanistan, Morocco, Jordan, Azerbaijan, and Iran to protect from the evil eye. Its extract is also used to induce abortion and menstruation. Its con-sumption as an antiparasitic agent, especially as an anti-worm, was already a common practice.A red agent is released from boiled Esfand, which is used in the carpet industry. According to studies, Pega-num harmala has analgesic effects (central and periph-eral) and can suppress the pain if used with naloxone, in which its mechanism of action is similar to opioids [1, 2]. A study also showed that high doses of Esfand can reduce spermatogenesis in mice [3]. This plant has β-carboline alkaloids with Monoamine Oxidase (MAO) inhibitory effects. One of these alkaloids is harmine. Harmine is a neurotoxin and an endogenous ligand of benzodiazepine receptors that is believed to have strong correlation with essential tremor. By selective and re-versible inhibition of MAO, harmine reduces the rate of monoamines destruction (neurotransmitters, hormones, ESummer 2018, Volume 8, Number 3120 Ataee Z, et al. Acute Poisoning With Peganum Harmala, Esfand. IJMTFM. 2018; 8(3):119-121.and psychotropic substances), which in turn increases their effects. Research studies show that the simultane-ous application of many kinds of hallucinogenic agents and harmine increases their effects [4, 5]. It also has cy-totoxic effects on the HL60 and K562 cell lines, that both of which are strongly associated with leukemia [6, 7].Harmine facilitates osteoblasts and chondrocytes dif-ferentiation, and prevents osteoclastogenesis. It is also proven that harmine plays a role in the proliferation of alpha and beta cells of pancreas; therefore, it can be used to treat diabetes. Harmine has anticholinesterase effects and prevents the breakdown of acetylcholine [8, 9]. Har-maline, harmalol, tetrahydroharmine, vasicine and va-sicinone have bronchodilatory effects [10]. Alkaloids of Esfand can form dangerous, even deadly, fission agents in reaction with antihistamines, antidepressants, decon-gestants, and expectorant, and some stimulants. In case of continuous use, sudden discontinuation of MAOIS can lead to a withdrawal syndrome, taking 30 to 300 mg of alkaloids in Esfand can lead to manifestation of the following symptoms: agitation, bradycardia or tachy-cardia, blurred vision, hypotension, paresthesia, nausea, vomiting and hallucinations [11, 12].2. Case presentationA 58-year-old female, accompanied by her husband, referred to Clinical Toxicology Service, complaining of nausea and abdominal pain. One hour before the visit, she consumed a glass (250 mL) of concentrated boiled Esfand seeds to reduce her blood glucose. Her complaints were limited to general weakness, dizziness, imbalance when walking, several episodes of nonbilious vomiting, and abdominal pain in epigastrium that was irritated and not prickled. She was a known case of diabetes mellitus type 2, since 15 years ago and was under metformin (one 500 mg tablet every eight hours) and glibenclamide (5 mg every six hours) treatment and a diabetic diet, with no other complaints. However, the physician prescribed her insulin in order to control her blood glucose. Physical examination revealed the patient’s vital signs: blood pressure: 140/80 mm Hg, pulse rate: 120 beats/min, respiratory rate: 21 breaths/min, pulse ox-imetry (O2Sat): 96%, the Glasgow coma scale: 14/15, Blood Sugar (BS) glucometry: 250 mg/dL, body tem-perature: 37.5°C. The patient had warm skin that her extremities were agitated with dermal stimulation. The pupils were miotic with decreased light reflex. She had no neck stiffness, oral mucosa was normal, the lungs were normal, but the patient had tachycardia, the abdo-men was soft and lacked tenderness. The organs were normal with no lateral symptoms, the tendon reflux were normal and symmetric. The patient was admitted to the poisoning department after gastric lavage with 3 liters of normal saline solution and administration of activated charcoal 70 g/kg.Of the clinical laboratory tests, the following mea-sures were remarkable: WBC: 25000/m3 with 63% polymorphs, RBC cholinesterase level>6.5 Unit, se-rum cholinesterase level <25% normal, HbA1C>8, ALT:123 Unit, AST;195, ALK PH:62, PT:14, PTT:36, AMYLASE:175, LIPASE:78, BS:250 mg/dL, k+:3 mEq, Ca+:7.5 mEq, Mg+:3 mEq, Na:145 mEq, LDH:770 Unit, CPK: 8000/Unit. In addition, the patient had no patho-logic symptoms and viral biomarkers were also negative.In toxicological profiling, the tests were negative for opioids and psychotropic substances, and organophos-phates and carbamate toxins. Arterial blood gas analysis revealed the following results: pH: 3.7, PCO2:60 mm Hg, HCO3:25 mEq/L. The patient was monitored and her agitation and tachycardia were controlled with oxy-gen therapy and administration of midazolam. Activated charcoal was also prescribed for 4 extra doses as 35 g daily plus sorbitol, followed by oral administration of ondansetron. After 2 days of hospital stay and requesting oncology and psychiatry counseling to convince the pa-tient to use insulin, instead of any traditional non-scien-tific treatment and supportive therapies, the patient was discharged in good condition. She was advised to refer to the poisoning clinic. The patient was free of specific complications caused by poisoning in follow-ups.Discussion: Peganum harmala, commonly called “Es-fand”, rooted in traditional medicine is still used by many people. Oral administration of 30-300 mg Esfand may lead to the toxic effects such as nausea, vomiting, abdominal pain, agitation, bradycardia or tachycardia, blurred vision, hypotension, paresthesia, and delusion. The half-life of harmala alkaloids in blood is 1-3 hours. In most studies conducted on animal models or sole de-scription of subjective or objective signs of the plant, no certain laboratory finding was reported in humans [5-8]. The treatment of this poisoning is also neglected in most studies [9-11]. Furthermore, in the absence of a his-tory or not mentioning the name of the consumed sub-stance, it is very difficult to detect this particular poison-ing. Because of bilateral miosis and higher prevalence of opioids in the region, the first clinical suspicion of such patients is poisoning with opioids or simultaneous poi-soning with opioids and psychotropic substances such as methamphetamine or clonidine, particularly, because Summer 2018, Volume 8, Number 3121Ataee Z, et al. Acute Poisoning With Peganum Harmala, Esfand. IJMTFM. 2018; 8(3):119-121.addicts use it for substance withdrawal purposes. On the other hand, consumption of insecticides and herbal pesticides is high in Iran and poisoning with such com-pounds should also be considered by clinicians. There-fore, it seems that taking a precise history from patient or his/her companions as well as accurate examination of the patient are of great importance. Overall, the im-portance of such measures in clinical practices should be noted and repeated for learners.3. ConclusionThe presented case was a prominent example of the im-portance of obtaining a precise history from a patient or his companions in order to prevent additional diagnostic and therapeutic measures, as well as imposing unneces-sary costs to the patients.Ethical ConsiderationsCompliance with ethical guidelinesAll information obtained from patients Will remain confidential.FundingThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.Conflict of interestThe authors certify that they have no affiliation with or involvement in any organization or entity with any finan-cial interest, or non- financial interest in the subject mat-ter or materials dismissed in this manuscript. All authors meet the four criteria of authorship contribution based on the recommendations of the international committee of medical journal editors.AcknowledgementsWe would like to express our special thanks to the Head of Hospital, Tehran, Iran.References[1] Farouk L, Laroubi A, Aboufatima R, Benharref A, Chait A. Evaluation of the analgesic effect of alkaloid extract of Pe-ganumharmala L.: Possible mechanisms involved. Journal of Ethnopharmacology. 2008; 115(3):449–54. [DOI:10.1016/j.jep.2007.10.014] [PMID][2] El-Dwairi QA, Banihani SM. Histo-functional effects of Peganumharmala on male rat’s spermatogenesis and fertil-ity. NeuroEndocrinol. Neuroendocrinology Letters. 2007; 28(3):305-10. [PMID][3] Hemmateenejad B, Abbaspour A, Maghami H, Miri R, Pan-jehshahin MR. Partial least squares-based multivariate spec-tral calibration method for simultaneous determination of beta-carboline derivatives in Peganum harmala seed extracts. Analytica Chimica Acta. 2006; 575(2):290–9. [DOI:10.1016/j.aca.2006.05.093] [PMID][4] Louis ED, Zheng W, Jiang W, Bogen KT, Keating GA. Quan-tification of the neurotoxic beta-carboline harmane in barbe-cued/grilled meat samples and correlation with level of done-ness. Journal of Toxicology and Environmental Health, Part A. 2007; 70(12):1014–9. [DOI:10.1080/15287390601172015] [PMID] [PMCID][5] Rommelspache H, Nanz C, Borbe HO, Fehske KJ, Müller WE, Wollert U. 1-Methyl-β-carboline (Harmane), a potent endogenous inhibitor of benzodiazepine receptor binding. Naunyn-Schmiedeberg’s Archives of Pharmacology. 1980; 314(1):97-100. [DOI:10.1007/BF00498436] [PMID][6] Louis ED, Zheng W, Jurewicz EC, Watner D, Chen J, Factor Litvak P, et al. Elevation of blood β-carboline alkaloids in essen-tial tremor. Neurology. 2002; 59(12):1940-4. [DOI:10.1212/01.WNL.0000038385.60538.19] [PMID] [PMCID][7] Jahaniani F, Ebrahimi SA, Rahbar Roshandel N, Mahmou-dian M. Xanthomicrol is the main cytotoxic component of Dracocephalum Kotschyii and a potential anti-cancer agent. Phytochemistry. 2005; 66(13):1581-92. [DOI:10.1016/j.phytoo-chem.2005.04.035] [PMID][8] Yonezawa T, Lee JW, Hibino A, Asai M, Hojo H, Cha BY, et al. Harmine promotes osteoblast differentiation through bone morphogenetic protein signaling. Biochemical and Biophysical Research Communications. 2011; 409(3):260–265. [DOI:10.1016/j.bbrc.2011.05.001] [PMID][9] Hara ES, Ono M, Kubota S, Sonoyama W, Oida Y, Hattori T, et al. Novel chondrogenic and chondroprotective effects of the natural compound harmine. Biochimie. 2013; 95(2):374-81. [DOI:10.1016/j.biochi.2012.10.016] [PMID][10] Egusa H, Doi M, Saeki M, Fukuyasu S, Akashi Y, Yokota Y, at al. The small molecule harmine regulates NFATc1 and Id2 expression in osteoclast progenitor cells. Bone. 2011; 49(2):264-74. [DOI:10.1016/j.bone.2011.04.003] [PMID][11] Zheng XY, Zhang ZJ, Chou GX, Wu T, Cheng XM, Wang CH, et al. Acetylcholinesterase inhibitive activity-guided isolation of two new alkaloids from seeds of peganum ni-gellastrum bunge by an in vitro TLC-bioautographic assay. Archives of Pharmacological Research. 2009; 32(9):1245-51. [DOI:10.1007/s12272-009-1910-x] [PMID][12] Avula B, Begum S, Ahmed S, Choudhary MI, Khan IA. Quantitative determination of vasicine and vasicinone in Ad-hatoda vasica by high performance capillary electrophoresis. Die Pharmazie- An International Journal of Pharmaceutical Sciences. 2008; 63(1):20-2.Summer 2018, Volume 8, Number 3

Acute Poisoning With Peganum Harmala, Esfand: A Rare Case Report

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Acute Poisoning With Peganum Harmala, Esfand: A Rare Case Report

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