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SQUIRTING CUCUMBER [ Ecballium elaterium ( L .) A. Richard]

Medical Toxicology of Natural Substances, by Donald G. Barceloux, MDCopyright © 2008 John Wiley & Sons, Inc.

HISTORY

The use of the juice from the squirting cucumber for the treatment of chronic sinusitis dates back to the writings of Dioscorides (20 – 79 AD) in the Materia Medica . The Greek philosopher Theophrastus mentioned this plant in his history of plants.

BOTANICAL DESCRIPTION

Common Name: Squirting Cucumber, Jumping Cucumber, Donkey ’ s Green

Scientifi c Name: Ecballium elaterium (L.) A. Richard

Botanical Family: Cucurbitaceae (citrouilles, gourdes, gourds, squashes)

Physical Description: This hairy vine has palmately lobed, bristly leaves. The funnel - shaped, yellow fl owers produce hairy, blue - green seed pods, which eject dark seeds and juice after maturity in response to light pressure. Both male and female fl owers appear on the same plant.

Distribution and Ecology: This perennial vine grows in hot, dry areas on disturbed ground and road-sides in the Mediterranean region and Micronesia. It is cultivated in central Europe and England.

EXPOSURE

The diluted (i.e., up to 30 : 1) aqueous extract from the fruit of Ecballium elaterium is a traditional anti - infl ammatory and analgesic for chronic sinusitis by nasal

aspiration. 1,2 Other traditional uses include the treat-ment of fever, cancer, liver cirrhosis, constipation, hyper-tension, dropsy, and rheumatic diseases. 3

PRINCIPAL TOXINS

Physiochemical Properties

Cucurbitacin compounds (CAS RN: 60137 - 06 - 6, C 30 H 42 O 6 ) are a group of colorless, bitter, highly oxygen-ated triterpenoid substances characterized by the tetracyclic cucurbitane nucleus [19 - (10 → 9 β ) - abeo - 10 α - lanost - 5 - ene]. 4,5 These compounds are present in several other plant species including Citrullus colocynthis (L.) Schrad. (colocynth, bitter apple). Figure 154.1 displays the chemical structure of cucurbitacin B (RN: 6199 - 67 - 3, C 32 H 46 O 8 ), which is the principal anti - infl ammatory compound in the squirting cucumber. 6,7

Poisonous Parts

All parts of the squirting cucumber are toxic, particu-larly the ovoid green fruits. The juice of the fruit pro-duces dermal erythema, infl ammation, and edema.

Mechanism of Toxicity

Although cucurbitacin B has been identifi ed as the active anti - infl ammatory compound in the squirting cucumber, the ingredient or ingredients causing severe irritation to mucus membranes are unknown. The mech-anism of toxicity (i.e., direct toxic effect, hypersensitivity response) is also not well defi ned, but the clinical

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effects often do not respond to antihistamines or epinephrine. 8

DOSE RESPONSE

Cases of severe mucus membrane swelling typically involve the use of undiluted juice from the squirting cucumber. Traditionally, the juice is diluted 3 – 30 times before nasal aspiration for the treatment of chronic sinusitis.

TOXICOKINETICS

The toxic ingredient in squirting cucumber has not been identifi ed, and there are no human data on the toxico-kinetics of constituents (e.g., cucurbitacins) in the juice of squirting cucumber.

CLINICAL RESPONSE

The undiluted juice from the squirting cucumber causes marked infl ammation of mucous membranes and local-ized edema following ingestion, instillation in the nasal cavities, or ocular exposure. Most patients with adverse responses to this juice have multiple allergies, and previ-ously may have used the juice without complications. 9 Symptoms begin within 10 – 20 minutes of exposure and persist for 24 – 48 hours. 10 Progression of the infl amma-tion can cause conjunctival irritation, corneal edema and erosions, sore throat, dysphagia, drooling, dyspnea, or respiratory distress secondary to upper airway edema (soft palate, uvula). 11 Obstruction of the upper airway is a potentially fatal complication of the nasal installation of undiluted juice from the squirting cucumber. 12 A case report associated the development of progressive facial and pharyngeal edema, fever, respiratory distress, renal insuffi ciency, and cardiac failure over 5 days with the use of four to fi ve nasal aspirations of diluted juice from the

squirting cucumber. 13 The patient died on the sixth day after exposure to the juice, but the role of the exposure to this juice is unclear because of the lack of medical details (blood cultures, oxygen saturations, imaging studies) and the failure to exclude other causes (sepsis, cardiovascular/renal disease).

DIAGNOSTIC TESTING

Laboratory measurements of hepatorenal function and serum electrolytes typically are normal after exposure to the undiluted juice of the squirting cucumber with the exception of laboratory evidence of airway obstruction. 14

TREATMENT

Patients should be evaluated carefully for the presence of upper airway obstruction (stridor, drooling, dyspnea, tachypnea, reduced oxygen saturation). The respiratory effects associated with exposure to the squirting cucum-ber usually occur within minutes to a few hours after exposure. Although the exact mechanism of toxicity is unclear, treatment of the severe upper airway edema following exposure to undiluted juice from the squirting cucumber typically involves medicines to treat anaphy-lactic responses including the use of epinephrine (0.3 – 0.5 mL 1 : 1000 solution SQ), intravenous H 1 - (diphenhydramine) and H 2 - (ranitidine or cimetidine) histamine blockers, and intravenous methylpredniso-lone. However, the swelling may not respond to these agents, and prophylactic intubation may be necessary in severe cases. Ocular exposure to the undiluted juice should be treated with copious irrigation followed by slit lamp examination to detect corneal erosions.

References

1. Sezik E , Yesilada E . Clinical effects of the fruit juice of Ecballium elaterium in the treatment of sinusitis . J Toxicol Clin Toxicol 1995 ; 33 : 381 – 383 .

2. Uslu C , Karasen RM , Sahin F , Taysi S , Akcay F . Effect of aqueous extracts of Ecballium elaterium rich, in the rabbit model of rhinosinusitis . Int J Pediatr Otorhinolaryngol 2006 ; 70 : 515 – 518 .

3. Sezik E , Yesilada E , Honda G , Takaishi Y , Takeda Y , Tanaka T . Traditional medicine in Turkey X. Folk medicine in Central Anatolia . J Ethnopharmacol 2001 ; 75 : 95 – 115 .

4. Chen JC , Chiu MH , Nie RL , Cordell GA , Qiu SX . Cucur-bitacins and cucurbitane glycosides: structures and bio-logical activities . Nat Prod Rep 2005 ; 22 : 386 – 399 .

5. Seger C , Sturm S , Haslinger E , Stuppner H . A new cucur-bitacin D related 16,23 - epoxy derivative and its isomeriza-tion products . Organic Lett 2004 ; 6 : 633 – 636 .

FIGURE 154.1. Chemical structure of cucurbitacin B.

O

H3C CH3

H

CH3

HO

H

H3C

O CH3

OH

O

HO CH3

O

H3C

CH3 CH3

O

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6. Yesilada E , Ustun O , Sezik E , Takaishi Y , Ono Y , Honda G . Inhibitory effects of Turkish folk remedies on infl am-matory cytokines: interleukin - 1alpha, interleukin - 1beta and tumor necrosis factor alpha . J Ethnopharmacol 1997 ; 58 : 59 – 73 .

7. Yesilada E , Tanaka S , Sezik E , Tabata M . Isolation of an anti - infl ammatory principle from the fruit juice of Ecbal-lium elaterium . J Nat Prod 1988 ; 51 : 504 – 508 .

8. Eken C , Ozbek K , Yildirim CK , Eray O . Severe uvular edema and nasal mucosal necrosis due to Ecbalium elate-rium (squirting cucumber): an allergic reaction or direct toxic effect? Clin Toxicol 2008 ; 46 : 257 – 258 .

9. Kloutsos G , Balatsouras DG , Kaeros AC , Kandiloros D , Ferekidis E , Economou C . Upper airway edema resulting from use of Ecballium elaterium . Laryngoscope 2001 ; 111 : 1652 – 1655 .

10. Raikhlin - Eisenkraft B , Bentur Y . Ecbalium elaterium (squirting cucumber) — remedy or poison? Clin Toxicol 2000 ; 38 : 305 – 308 .

11. Koussidis GA , Mountantonakis S , Petrichou CC . Folk remedies still in use: a case of soft palate and uvular oedema due to Ecballium elaterium . Int J Clin Pract 2002 ; 56 : 817 .

12. Satar S , Gokel Y , Toprak N , Sebe A . Life - threatening uvular angioedema caused by Ecballium elaterium . Eur J Emerg Med 2001 ; 8 : 337 – 339 .

13. Vlachos P , Kanitsakis NN . Fatal cardiac and renal failure due to Ecballium elaterium (squirting cucumber) . Clin Toxicol 1994 ; 32 : 737 – 738 .

14. Eray O , Tuncok Y , Eray E , Gunerli A , Guven H . Severe uvular angioedema caused by intranasal administration of Ecballium elaterium . Vet Hum Toxicol 1999 ; 41 : 376 – 378 .