Human Exposure to Ecballium elaterium Fruit Juice: Fatal Toxicity and Possible Remedy

Abstract

The human serious adverse reactions of the folkloric plant, Ecballium elaterium (EE), are well documented in the literature. This report is presenting the medical literature of 74 cases, which experienced severe adverse reactions or deaths that resulted from the administration of the plant juice. The survey of these human cases exhibits several adverse effects such as: acute rhinitis, uvular edema, soft palate, upper airway edema. In conclusion, the use of EE juice in folk medicine can cause severe adverse reactions that should not be ignored but it should be medically treated.

Share and Cite:

A. Salhab, "Human Exposure to Ecballium elaterium Fruit Juice: Fatal Toxicity and Possible Remedy," Pharmacology & Pharmacy, Vol. 4 No. 5, 2013, pp. 447-450. doi: 10.4236/pp.2013.45064.

1. Introduction

The plant EE, known as squirting cucumber, is a weed belongs to cucurbitacea family. The plant is perennial, fleshy, rough hairy with stems 30 - 100 cm long. The flowers are greenish-yellow and the fruit are large juicy berry, 3 - 4 cm, ovate-oblong, detaching itself explosively at maturity scattering seeds and juice (Figure 1). The plant is widely distributed in the Mediterranean countries. In Jordan, it grows wild in many places including the roadsides and cultivated areas [1].

The fresh juice of EE had been used in folk medicine to treat jaundice since antiquities. Avicenna (980 - 1037) described the use of the juice in his famous book, ALKannon, almost one thousand years ago [2]. Nowadays, the people in Jordan as well as in other countries, are using the juice in the treatment of acute and chronic jaundice, rhinosinusitis, sinusuitis, and other ailments of inflammations [3-8].

The fruit juice of the plant contains several bioactive ingredients such as cucurbitacins. These tetracyclic triterpenoids compounds such as A, E, D, I are of interest medicinally because of their cytotoxic, antitumor and antijaundice properties.

Still these bioactive compounds have been reported to possess other pharmacological activities for example: purgatives, analgesics and hemorrhoids [6,7,9-11].

The purpose of this report is to present a recent review the medical available literature of seventy three human cases as appeared in the Pub-med and other available literature. Further to discuses the possibility of safely use of the plant juice despite its life-threatening adverse effects.

2. Results

Literature Search

Pub med was used to search for patients whom treated by EE juice for jaundice and other ailments. It was possible to allocate 73 different human cases. All of these cases are presented in (Table 1) [Pub-Med: 3,12,14-22]. One

Figure 1. Ecballium elaterium plant (Amman, countryside, Summer, 2010).

Table 1. Reported folkloric cases of patients exposed to Ecballium elaterium fruit juice.

more new case was the Jordanian female of two months old neonate (Personal communication with Professor Najwa Khori of Pediatrics Department, Faculty of Medicine, University of Jordan, Amman, Jordan).

2.1.1. The Folkloric Use

As presented in (Table 1), the plant juice was used to treat: jaundice; chronic sinusitis; acute rhinosinusitis; sinusitis; acute maxillary sinuate; sinusitis and liver cirrhosis.

2.1.2. Administration

The patients were to receive intranasal administration of few undiluted drops of fresh juice.

2.1.3. Age and Sex

The patients were to include males or females of different ages (Table 1).

2.1.4. Adverse Effects of EE Juice

Patients were admitted to the emergency services with various complaints and different signs and symptoms such like: burning sensation, sore throat, difficulty of breathing, soft palate, uvular angioedema, difficulty of swallow, conjunctivitis (eye exposure), allergic reactions, renal and heart failure and even death (Table 1).

2.1.5. Treatment in the Emergency Room

All patients were treated asymptomatically, depends on the signs and symptoms and the condition of the patient. Since, the respiratory system was the major system which was affected by EE Juice, therefore, treatment were to involve the administration of: oxygen, antihistamines, prednisolone, or epinephrine. The eye and skin exposures were treated topically by corticosteroids and antibiotics. Ninety Seven percent of patients were dismissed shortly after recovery (Table 1).

3. Discussion

Jaundice usually comprises a yellow discoloration of the skin and the sclera that produced by accumulations of bilirubin in the tissues and interstitial fluids. It is resulted from increased of bilirubin load and decrease of bilrubin elimination [22,23]. Furthermore, Juandice is still a common physiological problem affecting over half of all fullterm and most preterm infants [23-25]. Although, jaundice is mainly harmless, still the jaundiced of the newborn infant must be monitored for its subsequent consequences such as: hyperbilirunbinemia, acute encephalopathy, and kernictures. At daylight, usually bilirubin becomes visible when the concentration of plasma bilirubin exceeds 2% - 3% mg.The most common causes of jaundice are usually resulted from: increasing of the destruction of red blood cells, the obstruction of the bile ducts and the damage liver hepatocytes [22,23].

The mainstay treatment and intervention of Jaundice is by phototherapy, exchanging transfusion, using of medication such as phenobarbital, baby body massage, and the use of herbal medicine.

The combination of four herbs that sound promising: Artemesia capillaries, Gardenia jasminoides Ellis, Rheum officinale Baill, and Scutellaria baicalensis. This combination is called Yin Zhi Huang combination [25,26]. The use of combination and phenobarbital was found to be useful since phenobarbital induced the activity of the enzyme bilirubin glucoronyltranferase, while, the combination has a potent stimulatory effect on bilirubin clearance through the induction of the activity of the nuclear receptor (CAR) [25]. At the meantime, Huang, et al., 2004 reported that the combination enhances bilirubin clearance by activating the nuclear receptor (androstane receptor, CAR) [25].

However, in our previous investigation using four different animal species models [27], we reported, that EE juice resulted a significant marked decrease in bilirubin presented in the serum in a dose related manor. Therefore, the exact mechanism(s) of the juice has to be clarified in future researches.

4. Conclusion

In conclusion, the nostril administration of EE juice, although resulted of serious adverse reactions and even deaths, of patients, still comprehensive research protocols have to be developed to test the safety and the efficacy of the juice.

5. Acknowledgements

The author would to acknowledge the help of the professor Najwa Khoury for her personal communication, and Khaled A Salhab for his secretarial help.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] B. Abu-Irmeileh, “Weeds of Jordan (Book),” Publication of the University of Jordan, Amman, 1982.
[2] J. Jabour, “Al-kannon in Medicine of Avicenna (Book),” Al-Ma’ref Library, Beirut, 1983.
[3] E. A. Mazokopakis, C. M. Karefilakis and I. K. Starakis, “The Safety and Efficacy of the Fruit Juice of Ecballium elaterium in the Treatment of Acute Rhinosinusitis,” The Journal of Alternative and Complementary Medicine, Vol. 15, No. 2, 2009, pp. 1273-1274. doi:10.1089/acm.2009.0241
[4] G. Worall, “Acute Sinusitis,” Canadian Family Physician, Vol. 54, 2008, pp. 82-83
[5] E. Cezik and E. Yesilada, “Clincal Effects of the Juice of Ecbalium elaterium in the Treatment of Sinusitis,” Clinical Toxicology, Vol. 33, No. 4, 1995, pp. 381-383. doi:10.3109/15563659509028931
[6] E. Yesilada, S. Tanaka, E. Sezik and M. Tabata, “Isolation of Anti-Inflammatory Principle from the Fruit Juice of Ecballium elaterium,” Journal of Natural Products, Vol. 51, No. 3, 1988, pp. 504-508. doi:10.1021/np50057a008
[7] H. Greige-Gerges, R. A. Khalil, E. A. Mansour, J. Magdalou, R. Chahine and N. Quaini, “Cucurbitacins from Ecballium elaterium Juice Increase the Binding of Bilirubin and Ibuprofen to Albumin in Human Plasma,” Chemico-Biological Interactions, Vol. 169, No. 1, 2007, pp. 53-62. doi:10.1016/j.cbi.2007.05.003
[8] A. S. Salhab, H. H. Elayan, M. N. Ghraibeh and S. Amer, “The Acute Toxicity of the Juice of Ecballium elaterium Rich,” Dirasat, Vol. 8, No. 11, 1986, pp. 91-99.
[9] D. Lavi and D. Willner, “The Constituent of Ecballium elatrrium L. III. Elatrecein A and B,” Journal of the American Society, Vol. 80, No. 3, 1985, pp. 710-714. doi:10.1021/ja01536a047
[10] J. L. Hartwell, “Types of Anticancer Agents Isolated from Plants,” Cancer Treatment Report, Vol. 60, No. 8, 1976, pp. 1031-1067.
[11] G. A. Cordell and N. R. Fransworth, “Expermental Antitumer Agents,” Journal of Natural Products, Vol. 40, No. 60, 1977, pp. 1-66.
[12] G. Kloutsos, D. G. Balatsouras, A. C. Kaberos, et al., “Upper Airway Edema Resulting from Use of Ecbalium elaterium,” Laryngoscope, Vol. 111, No. 9, 2001, pp. 1652-1655. doi:10.1097/00005537-200109000-00030
[13] I. Kocak, Y. Kaabela, M. Karaman and F. Kaya, “Latee Lamellar Keratitis as a Result of the Toxic Effects of Ecballium elaterium Herb,” Journal of Refractive Surgery, Vol. 22, No. 8, 2006, pp. 826-827.
[14] S. Satar, Y. Gokel, N. Toprak and A. Sebe, “Life-Threatening Uvular Angioedema Caused by Ecbalilium elaterium,” European Journal of Emergency Medicine, Vol. 8, No. 4, 2001, pp. 337-339. doi:10.1097/00063110-200112000-00018
[15] B. Raiklin-Eisenkraft and Y. Bentur, “Ecballium elaterium (Squirting Cucumber): Remedy or Poison?” Clinical Toxicology, Vol. 38, No. 3, 2000, pp. 305-308. doi:10.1081/CLT-100100936
[16] I. Kokkonouzis, G. Antonio, S. Varvaressos, G. Konstantopoulos, V. Ntouli, P. Vergou and V. Myidaki, “Upper Airway Edema Due to Nasal Aspiration of Undiluet Juice of Ecballium elaterium: Report of Three Cases,” American Journal of Case Reports, Vol. 9, 2008, pp. 255-258.
[17] G. A. Koussidis, S. Mountantonakis and C. C. Petrichou, “Folk Remedies Still in Use, a Case of Soft Palate Uvular Edema Due to Ecballium,” International Journal of Clinical Practice, Vol. 56, No. 10, 2002, p. 817.
[18] O. Eray, Y. Tuncok, E. Eray, A. Gunerli and H Guven, “Severe Uvular Angioedema Caused by Intranasal Administration of Ecballium elaterium,” Veterinary and Human Toxicology, Vol. 41, No. 6, 1999, pp. 376-378.
[19] P. Apostolos, P. Athanasios, G. Georgios, S. Charalambos, L. Emmanouil, D. Loannis, C. Loannis, K. Anastasia and A. Georgios, “Severe Uvular Edema and Resulting Hypoxemia Due to Single Use of Ecballium elaterium Extract,” American Journal, Vol. 13, 2012, pp. 11-13.
[20] P. Vlachos, N. N. Kanitsakis and N. Konsas, “Fatal Cardiac and Renal Failure Due to Ecballium elaterium (Squirting Cucumber),” Clinical Toxicology, Vol. 32, No. 6, 1994, pp. 737-738. doi:10.3109/15563659409017981
[21] K. Aydogan, S. Yazici and H. Turan, “A Rare Reason for Uvular Angioedema: Ecballium elaterium,” Annals of Dermatology, Vol. 24, No. 3, 2012, pp. 358-359. doi:10.5021/ad.2012.24.3.358
[22] C. Eken, K. Ozbek, C. K. Yildirim and O. Eray, “Severe Uvular Edema and Nasal Muosal Necrosis Due to Ecballium elaterium (Squirting Cucumber): An Allergic Reaction or Direct Toxic Effect?” Clinical Toxicology, Vol. 46, No. 3, 2008, pp. 257-258. doi:10.1080/15563650601158834
[23] P. A. Dennery, D. S. Seidman and D. K. Stevenson, “Neonatal Hyperbilirubinnemia,” The New England Journal of Medicine, Vol. 344, 2001, pp. 581-590. doi:10.1056/NEJM200102223440807
[24] P. A. Dennery, “Pharmacological Intervention for the Treatment of Neonatal Jaundice,” Seminars in Neonatology, Vol. 7, No. 2, 2002, pp. 111-119. doi:10.1053/siny.2002.0098
[25] W. Huang, J. Zhang and D. D. Moore, “A Traditional Herbal Medicine Enhances Bilirubin Clearance by Activating the Nuclear Receptor,” The Journal of Clinical Investigation, Vol. 113, No. 1, 2004, pp. 137-143.
[26] J. Yin, M. Miller and R. P. Wennberg, “Induction of Hypatic Bilirubin Metabolizing Enzymes by the Traditional Chinese Medicine Yin Zhi Hung,” Developmental Pharmacology and Therapeutics, Vol. 16. No. 3, 1991, pp. 176-184.
[27] H. H. Elayan, M. N. Gharaibeh, S. M. Zmmeili and A. S. Salhab, “Effects of Ecballium elaterium Juice on Serum Bilirubin Concentration in Male Rats,” International Journal of Crude Drug Research, Vol. 27, 1984, pp. 227-238.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.