Hepatitis after Germander (<i>Teucrium chamaedrys</i>) Administration: Another Instance of Herbal Medicine Hepatotoxicity

Larrey, Dominique; Vial, Thierry; Pauwels, Arnaud; Castot, A; Biour, M; David, Martine; Michel, H

doi:10.7326/0003-4819-117-2-129

Cited by 247 publications

(143 citation statements)

References 14 publications

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“…Chromium (III) oxide and 4-(dibiatae family, has been used occasionally since ancient times methylamino)benzaldehyde were purchased from Sigma-Aldrich as a folk medicine. 1 Aerial parts of the plant in bloom were (L'Isle-D'Abeau-Chesnes, France). All solvents were from Prolabo used to prepare herbal teas with alleged choleretic and anti-(Paris, France) and were distilled before use.…”

Section: Chemicalsmentioning

confidence: 99%

“…NADPH, collagenase septic properties. 1 Germander was also used, for its bitter A (from Clostridium histolyticum), reduced glutathione (GSH), and tonic and appetizer properties, as a minor constituent in some GSH reductase were purchased from Boehringer (Mannheim, Germany). Sephadex G25 was purchased from Pharmacia (Uppsala, liqueurs.…”

Section: Chemicalsmentioning

confidence: 99%

“…The furano diterpenoid fraction penoids (NCD). 1,2,5 In a previous study, we have shown that decreased cell glutathione and cytoskeleton-associated the in vivo hepatotoxicity of germander was reproducible in protein thiols, and led to formation of plasma membrane mice and was entirely caused by the toxicity of its furano blebs and cell demise. Pretreatment of male rats with NCD.…”

mentioning

confidence: 99%

“…1 Promotion in this particular indication, added to Several herbal remedies have produced hepatitis in the general fad for ''natural'' medicines, suddenly led to humans. The medicinal plant, germander, was recalled large-scale utilization, and to an epidemic of hepatitis in after its use as an adjuvant to slimming diets resulted France.…”

mentioning

confidence: 99%

“…The medicinal plant, germander, was recalled large-scale utilization, and to an epidemic of hepatitis in after its use as an adjuvant to slimming diets resulted France. [1][2][3][4] Following the report of 26 cases of cytolytic hepatiin an epidemic of hepatitis in France. We studied the tis to the French Regional Centers of Pharmacovigilance, 2 hepatotoxicity of germander in isolated rat hepatocytes.…”

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confidence: 99%

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Hepatotoxicity of the Herbal Medicine Germander: Metabolic Activation of Its Furano Diterpenoids by Cytochrome P450 3A Depletes Cytoskeleton–Associated Protein Thiols and Forms Plasma Membrane Blebs in Rat Hepatocytes

et al. 1996

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diets. 1 Promotion in this particular indication, added to Several herbal remedies have produced hepatitis in the general fad for ''natural'' medicines, suddenly led to humans. The medicinal plant, germander, was recalled large-scale utilization, and to an epidemic of hepatitis in after its use as an adjuvant to slimming diets resulted France. In a previous study, we have shown that decreased cell glutathione and cytoskeleton-associated the in vivo hepatotoxicity of germander was reproducible in protein thiols, and led to formation of plasma membrane mice and was entirely caused by the toxicity of its furano blebs and cell demise. Pretreatment of male rats with NCD. 6 These observations were subsequently confirmed by troleandomycin, an inhibitor of cytochrome P450 3Aanother in vivo study in mice. 7 The in vivo hepatototoxicity (CYP3A), slowed the depletion of glutathione and deof the furano NCD of germander was prevented by preadmincreased toxicity, whereas dexamethasone, an inducer of istration of a single dose of troleandomycin, 6 a specific inhibi-CYP3A, had opposite effects. Female rat hepatocytes, tor of cytochrome P450 3A (CYP3A), 8 and was enhanced by which poorly express CYP3A, exhibited little toxicity, pretreatment with either dexamethasone or clotrimazole, 6 unless the animals were treated with dexamethasone.two inducers of CYP3A, 8,9 whereas pretreatment with either Feeding male rats with a sulfur amino acid-deficient 3-methylcholanthrene or phenobarbital had no effect. 6 It was diet decreased cell glutathione and enhanced toxicity, concluded that CYP3A transformed the furano NCD of gerwhereas supplementation of the standard diet with cysmander into hepatotoxic metabolites. 6 However, it could not tine had opposite effects. We conclude that the furano be determined whether these hepatotoxic metabolites were diterpenoids of germander are activated by CYP3A into stable or reactive ones, and what were the molecular mechaelectrophilic metabolites that deplete glutathione and nisms responsible for their toxicity. 6,7 cytoskeleton-associated protein thiols and form plasmaIn the present study, these questions have been answered membrane blebs. We suggest that studies in isolated hein isolated rat hepatocytes. patocytes be included in the preclinical assessment of herbal remedies. (HEPATOLOGY 1996;24:212-218.) MATERIALS AND METHODS

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Section: Chemicalsmentioning

confidence: 99%

Section: Chemicalsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Hepatotoxicity of the Herbal Medicine Germander: Metabolic Activation of Its Furano Diterpenoids by Cytochrome P450 3A Depletes Cytoskeleton–Associated Protein Thiols and Forms Plasma Membrane Blebs in Rat Hepatocytes

et al. 1996

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Herbs as Medicines

Winslow

Kroll²

1998

Arch Intern Med

308

156

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Herbs and related products are commonly used by patients who also seek conventional health care. All physicians, regardless of specialty or interest, care for patients who use products that are neither prescribed nor recommended. Some herbs have been extensively studied, but little is known about others. When a patient asks for advice regarding the use of a particular herb, how should a physician respond? Similarly, how does a physician determine if a patient's symptoms are caused by a "remedy"? This review attempts to answer these questions by investigating pertinent definitions, the history of herbs in medicine, epidemiology and prevalence of herbal use, and relevant psychosocial issues.

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The Clinical Spectrum of Jin Bu Huan Toxicity

Horowitz

Feldhaus²,

Dart³

et al. 1996

Arch Intern Med

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Herbal medications and other nontraditional medical therapies are becoming increasingly popular in the United States. We describe three children and three adults in whom severe toxic effects developed after ingestion of a Chinese herbal medication, jin bu huan, which is sold as Jin Bu Huan Anodyne Tablets. Jin bu huan produced distinct clinical syndromes after acute ingestion in children and long-term use in adults. A single, acute ingestion in children rapidly produced life-threatening neurologic and cardiovascular manifestations, while long-term jin bu huan use in adults was associated with hepatitis. Jin bu huan contains levo-tetrahydropalmatine, a potent neuroactive substance. The constituents of jin bu huan are misidentified on the package, resulting in significant delay in identifying the plant alkaloid responsible for its toxicity. Although perceived as innocuous, jin bu huan may produce major health effects. The highly concentrated formulation, the lack of childproof packaging, and the product insert listing indications for the treatment of serious medical conditions may all contribute to the development of toxic reactions.

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Hepatitis after Germander (Teucrium chamaedrys) Administration: Another Instance of Herbal Medicine Hepatotoxicity

Abstract: Germander may be hepatotoxic, which supports the view that herbal medicines are not always as safe as generally assumed.

Cited by 247 publications

References 14 publications

Hepatotoxicity of the Herbal Medicine Germander: Metabolic Activation of Its Furano Diterpenoids by Cytochrome P450 3A Depletes Cytoskeleton–Associated Protein Thiols and Forms Plasma Membrane Blebs in Rat Hepatocytes

Hepatotoxicity of the Herbal Medicine Germander: Metabolic Activation of Its Furano Diterpenoids by Cytochrome P450 3A Depletes Cytoskeleton–Associated Protein Thiols and Forms Plasma Membrane Blebs in Rat Hepatocytes

Herbs as Medicines

The Clinical Spectrum of Jin Bu Huan Toxicity

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