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PLANTS-AESCULIN

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Aesculin is the glycoside found in the leaves and bark of various species of the genus Aesculus. Aescin is a saponin glycoside found in the seeds of the horse chestnut or buckeye. Aescin is sometimes used as a collective term for the mixture of saponins found in these species (Lampe & McCann, 1985).

Specific Substances

    A) Aescin
    1) Escin
    2) Aescusan
    3) Reparil
    Aesculin
    1) Esculin
    2) 6,7 dihydroxycoumarin-6-glucoside
    3) Esculoside
    4) Bicolorin
    5) Enallachrome
    6) Polychrome
    7) Escosyl

Available Forms Sources

    A) FORMS
    1) TOXIC PART: The young leaves and flowers are considered the most toxic part, but the bark (which is rarely eaten) contains the most aesculin (Cooper & Johnson, 1984).
    2) SEEDS CONTAIN: Starch, short chain fatty acids esters of various triterpenoid aglycones (including protoaescigenin) and 3 to 28% of a mixture of saponins (Frohne & Pfander, 1984; Karuza-Stojakovic et al, 1989).
    3) AESCIN AMOUNTS: Varies during a seed's development. In a growing season from mid-June to mid-October, the peak quantity is in mid-July to mid-August. The amount then decreases and when the nut covering is actually splitting, the aescin amount has dropped to 45% of its peak amount (Karuza-Stojakovic et al, 1989; Karuza-Stojakovic et al, 1991).
    4) SAPONINS: New saponins and aliphatic esters continue to be found in various Aesculus species (Singh et al, 1987; Singh et al, 1989).
    B) USES
    1) Aescin and various horse chestnut extracts have been used in medicine for their capillary-sealing, anti-inflammatory activity, tumour suppression, and anti-edema actions (Frohne & Pfander, 1984; Singh et al, 1986; Anisimov et al, 1978).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) Human horse chestnut or buckeye poisonings resulting from a single seed usually present as gastroenteritis only. Significant poisoning from these plants in unlikely.
    B) Although the horse chestnut-buckeye family is well known as a toxic group, there is an extremely small number of cases of poisoning in the literature. Because saponins (1) are poorly absorbed; (2) rarely affect adults; (3) horse chestnuts taste too bitter to swallow.
    C) No serious toxicity was reported in a large case series of horse chestnut (8 aesculus species) exposures. 77% of the cases reported no effect.
    D) Anaphylactic symptoms have occurred with intravenous and topical exposure to horse chestnut extract and aescin (a chemical isolated from the dried horse chestnut seeds).
    E) Older literature, generally with poor documentation, suggests that SEVERE POISONING, resulting from repeated ingestion of significant quantities, particularly by children, may present with incoordination, muscle weakness, and twitching, mucosal damage, mydriasis, vomiting, diarrhea, paralysis and CNS depression. There are extremely few cases of human exposure reported in the literature.
    0.2.6) RESPIRATORY
    A) Apnea may be seen due to paralysis of the respiratory muscles.
    0.2.7) NEUROLOGIC
    A) CNS depression, stupor, coma, muscle incoordination, paralysis, and headache have been seen in cases of human poisoning.
    0.2.8) GASTROINTESTINAL
    A) Vomiting and diarrhea may be seen after exposure to horse chestnuts.
    0.2.14) DERMATOLOGIC
    A) Contact dermatitis has been seen after contact with the young shoots of the yellow buckeye, Aesculus octandra.

Laboratory Monitoring

    A) These compounds are not analyzed through normal hospital procedures.
    B) Monitor fluid and electrolytes in severe cases of vomiting and diarrhea.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting.
    B) Most patients do not develop significant toxicity. Gastrointestinal decontamination is generally not indicated. Consider activated charcoal after very large ingestions.
    C) MONITOR FLUID and ELECTROLYTES and administer appropriate fluids when necessary.
    0.4.5) DERMAL EXPOSURE
    A) OVERVIEW
    1) DECONTAMINATION: Remove contaminated clothing and jewelry and place them in plastic bags. Wash exposed areas with soap and water for 10 to 15 minutes with gentle sponging to avoid skin breakdown. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

    A) A minimum lethal or minimum toxic dose has not been established. Toxicity from these agents is not a straight line phenomenon. Small amounts such as 1 or 2 seeds may only cause gastroenteritis.
    B) Large amounts, or small amounts ingested over several days, may cause significant mucosal irritation or destruction and therefore increase absorption which may produce systemic symptoms.
    C) In a large series of patients with horse chestnut ingestion 77% of patients developed no effects while 11% developed minimal effects.

Clinical Effects

Summary Of Exposure

    A) Human horse chestnut or buckeye poisonings resulting from a single seed usually present as gastroenteritis only. Significant poisoning from these plants in unlikely.
    B) Although the horse chestnut-buckeye family is well known as a toxic group, there is an extremely small number of cases of poisoning in the literature. Because saponins (1) are poorly absorbed; (2) rarely affect adults; (3) horse chestnuts taste too bitter to swallow.
    C) No serious toxicity was reported in a large case series of horse chestnut (8 aesculus species) exposures. 77% of the cases reported no effect.
    D) Anaphylactic symptoms have occurred with intravenous and topical exposure to horse chestnut extract and aescin (a chemical isolated from the dried horse chestnut seeds).
    E) Older literature, generally with poor documentation, suggests that SEVERE POISONING, resulting from repeated ingestion of significant quantities, particularly by children, may present with incoordination, muscle weakness, and twitching, mucosal damage, mydriasis, vomiting, diarrhea, paralysis and CNS depression. There are extremely few cases of human exposure reported in the literature.

Vital Signs

    3.3.3) TEMPERATURE
    A) FEVER has been seen in children ingesting horse chestnuts (Lampe & Fagerstrom, 1968).

Respiratory

    3.6.1) SUMMARY
    A) Apnea may be seen due to paralysis of the respiratory muscles.
    3.6.2) CLINICAL EFFECTS
    A) APNEA
    1) WITH POISONING/EXPOSURE
    a) Apnea may be seen due to paralysis of the respiratory muscles (Lampe & Fagerstrom, 1968).
    B) DYSPNEA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - Dyspnea and urticaria symptoms occurred in a 51-year-old male 30 minutes after topical application of aesculin (Escribano et al, 1997). Symptoms resolved completely with chlorpheniramine and corticosteroid therapy.
    C) OCCUPATIONAL ASTHMA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT - A 57-year-old male ex-smoker developed bronchial asthma after working with aescin in the pharmaceutical industry for 30 years, in contact with aescin. He experienced dry cough, dyspnea, sibilant wheezing, oppressive chest discomfort, and rhinitis for 10 years. His symptoms became aggravated after working with Plantago ovata 5 years before presentation. Specific inhalation challenge with aescin precipitated a 30% decrease in FEV1 and bronchospasm requiring bronchodilators (Munoz et al, 2006).

Neurologic

    3.7.1) SUMMARY
    A) CNS depression, stupor, coma, muscle incoordination, paralysis, and headache have been seen in cases of human poisoning.
    3.7.2) CLINICAL EFFECTS
    A) CENTRAL NERVOUS SYSTEM DEFICIT
    1) CNS depression, stupor and coma are symptoms seen in both man and animal intoxications (Williams & Olsen, 1984; (Hardin & Arena, 1965).
    B) HEADACHE
    1) Headache has been seen in children after ingesting horse chestnuts (Lampe & Fagerstrom, 1968).
    C) COORDINATION PROBLEM
    1) Muscle incoordination and twitching has been seen in both man and animals (Williams & Olsen, 1984; (Lampe & Fagerstrom, 1968).
    D) PARALYSIS
    1) Paralysis has been seen in man and animals (Nagy, 1973) Williams & Olsen, 1984; (Lampe & Fagerstrom, 1968).

Gastrointestinal

    3.8.1) SUMMARY
    A) Vomiting and diarrhea may be seen after exposure to horse chestnuts.
    3.8.2) CLINICAL EFFECTS
    A) VOMITING
    1) Vomiting has been noted in children who have eaten horse chestnuts (Lampe & McCann, 1985; Lampe & Fagerstrom, 1968). Oral irritation and gastrointestinal symptoms are some of the first seen in cases where a part or a single seed has been ingested (Frohne & Pfander, 1984).
    2) HORSE CHESTNUT/CASE SERIES - In a large case series of individuals exposed to 8 Aesculus species no serious toxicity occurred. Of the 571 symptomatic patients reported during 1993 and 1994, gastrointestinal symptoms (nausea, vomiting, diarrhea, and throat irritation) occurred in only 5% of the cases (Matyunas et al, 1997).
    B) EDEMA
    1) CASE REPORT - Autopsy done on a 4.5-year-old, who died after ingesting horse chestnuts over a couple of days, showed edema of the intestinal epithelium and lymph follicles with some sloughing of the stomach, distal part of the lower intestine and the entire colon (Lampe & Fagerstrom, 1968).

Hepatic

    3.9.2) CLINICAL EFFECTS
    A) TOXIC HEPATITIS
    1) A 37-year-old man developed abnormal liver function tests 17 days after receiving an injection of an anti-inflammatory agent (Venoplant) that is an extract of Aesculus Hippocastanum. Sixty days after injection he developed pruritis and jaundice. Total bilirubin, alkaline phosphatase and gamma GTP were elevated and he had mild eosinophilia. Liver biopsy revealed marked cholestasis with zonal centrilobular necrosis and a lymphocyte stimulation test was positive (Takegoshi et al, 1986).

Dermatologic

    3.14.1) SUMMARY
    A) Contact dermatitis has been seen after contact with the young shoots of the yellow buckeye, Aesculus octandra.
    3.14.2) CLINICAL EFFECTS
    A) CONTACT DERMATITIS
    1) The flowers and young shoots of Aesculus octandra are said to be able to produce contact dermatitis. The proprietary horse chestnut product called "Mano-Vausse" has produced dermatitis when taken orally and when applied as an ointment (Mitchell & Rook, 1979).

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) ANAPHYLACTOID REACTION
    1) Anaphylactic shock has been reported after IV injection of horse chestnut extracts (Wagner, 1965).
    2) CASE REPORT - A 51-year-old male developed generalized urticaria and dyspnea 30 minutes after topical application of a gel containing aesculin. Symptoms resolved following corticosteroid and chlorpheniramine (5 mg) therapy (Escribano et al, 1997).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) These compounds are not analyzed through normal hospital procedures.
    B) Monitor fluid and electrolytes in severe cases of vomiting and diarrhea.
    4.1.2) SERUM/BLOOD
    A) COAGULATION STUDIES
    1) Although aesculin is a close chemical relative to the warfarin-like anticoagulants, anticoagulation has NOT been a prominent clinical feature in poisonings in either humans or animals.
    B) BLOOD/SERUM CHEMISTRY
    1) Monitor fluid and electrolytes if significant vomiting and diarrhea are extensive.

Methods

    A) MULTIPLE ANALYTICAL METHODS
    1) Although these glycosides can be analyzed, the methods are not commonly available in hospitals.
    2) A radioimmunoassay has been developed for determination of picogram amounts of aescine. This radioimmunoassay covers the range of 100 picograms to 50 nanograms (Lehtola & Huhtikangas, 1990).
    3) The most common method of aescin determination is a spectrophometric method (Karuza-Stojakovic et al, 1989).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Monitoring

    A) These compounds are not analyzed through normal hospital procedures.
    B) Monitor fluid and electrolytes in severe cases of vomiting and diarrhea.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) SUMMARY
    1) Most patients do not develop significant toxicity. Gastrointestinal decontamination is generally not indicated. Consider activated charcoal after a very large ingestion.
    B) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    C) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) SUMMARY
    1) Most patients do not develop significant toxicity. Gastrointestinal decontamination is generally not indicated. Consider activated charcoal after a very large ingestion.
    B) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    C) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) DILUTION
    1) DILUTION: If no respiratory compromise is present, administer milk or water as soon as possible after ingestion. Dilution may only be helpful if performed in the first seconds to minutes after ingestion. The ideal amount is unknown; no more than 8 ounces (240 mL) in adults and 4 ounces (120 mL) in children is recommended to minimize the risk of vomiting (Caravati, 2004).
    B) SUPPORT
    1) Deaths which have been reported were due to deep coma and paralysis of the respiratory muscles. Good cardiac and respiratory support should be administered.
    C) AIRWAY MANAGEMENT
    1) Airway management including mechanical ventilation may be indicated in patients with evidence of severe toxicity including coma and respiratory muscle paralysis.
    D) FLUID/ELECTROLYTE BALANCE REGULATION
    1) Should be monitored and appropriate fluids administered.

Dermal Exposure

    6.9.1) DECONTAMINATION
    A) DERMAL DECONTAMINATION
    1) Remove contaminated clothing and jewelry and irrigate exposed areas with copious amounts of water. A physician may need to examine the area if irritation or pain persists (Burgess et al, 1999).

Range Of Toxicity

Summary

    A) A minimum lethal or minimum toxic dose has not been established. Toxicity from these agents is not a straight line phenomenon. Small amounts such as 1 or 2 seeds may only cause gastroenteritis.
    B) Large amounts, or small amounts ingested over several days, may cause significant mucosal irritation or destruction and therefore increase absorption which may produce systemic symptoms.
    C) In a large series of patients with horse chestnut ingestion 77% of patients developed no effects while 11% developed minimal effects.

Minimum Lethal Exposure

    A) GENERAL/SUMMARY
    1) A minimum lethal, or minimal toxic dose has not been established. Toxicity from these agents is not a straight line phenomenon. Small amounts, such as 1 or 2 seeds may only cause gastroenteritis.
    2) Large amounts, or small amounts ingested over several days, may cause significant mucosal irritation or destruction and thereby increase absorption and produce systemic toxicity.

Maximum Tolerated Exposure

    A) SUMMARY
    1) HORSE CHESTNUT/CASE SERIES - In a large study of individuals exposed to 8 Aesculus species, 3099 cases were analyzed from 1985 to 1994. Approximately, 50% of the exposures occurred in children between 0-5 years. 77% (2374) of the cases resulted in no effect/nontoxic; 11.5% (356) had minimum to moderate effects; the remaining 11.5% (359) were coded as unknown potentially toxic. The authors concluded that most exposures resulted in no toxic effect with no serious toxicity reported (Matyunas et al, 1997).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) In one study, the water soluble portion of alcoholic extracts of horse chestnuts, Ohio buckeyes, and yellow buckeyes, were tested on chicks and hamsters (Williams & Olsen, 1984). It was found that:

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Aesculin yields aesculetin (6,7-dihydroxycoumarin) on hydrolysis (Cooper & Johnson, 1984). Aesculin is related to the hydroxycoumarin found in spoiled sweet clover and from which the anticoagulant rodenticides have been developed (Frohne & Pfander, 1984).
    B) Aescin showed cytostatic activity in concentrations of 1.0 to 1.2 micrograms/mL (Anisimov et al, 1978).

Physicochemical

Physical Characteristics

    A) TASTE: Most chestnuts and buckeyes are said to have a bitter taste.

Ph

    A) > 5.8

Molecular Weight

    A) Aescin: approximately 1100
    B) Aesculin: 340

References

General Bibliography

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