 |
 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
15 April 1996 | Volume 124 Issue 8 | Pages 726-734
Background: Pennyroyal is a widely available herb that has long been used as an abortifacient despite its potentially lethal hepatotoxic effects. However, quantitative data for pennyroyal constituents and their metabolites in humans have not been previously reported.
Objectives: To quantify pennyroyal metabolites in human overdose, to correlate these findings with clinical variables, and to place these findings in the context of previously reported cases of pennyroyal toxicity.
Design: Clinical case series of pennyroyal ingestions; quantification of pennyroyal metabolites by gas chromatography and mass spectrometry; qualitative detection of protein-bound adducts of the metabolites of pennyroyal constituents in human liver by Western blot assay; and review of the literature based on a search of MEDLINE, Index Medicus, and the reference citations of all available publications.
Results: We report four cases of pennyroyal ingestion. One patient died, one received N-acetylcysteine, and two ingested minimally toxic amounts of pennyroyal and were not treated with N-acetylcysteine. In the fatal case, postmortem examination of a serum sample, which had been obtained 72 hours after the acute ingestion, identified 18 ng of pulegone per mL and 1 ng of menthofuran per mL. In a serum sample from the patient treated with N-acetylcysteine, which had been obtained 10 hours after ingestion, the menthofuran level was 40 ng/mL. Review of 18 previous case reports of pennyroyal ingestion documented moderate to severe toxicity in patients who had been exposed to at least 10 mL of pennyroyal oil.
Conclusion: Pennyroyal continues to be an herbal toxin of public health importance. Data on human metabolites may provide new insights into the toxic mechanisms and treatment of pennyroyal poisoning, including the potential role of N-acetylcysteine. Better understanding of the toxicity of pennyroyal may also lead to stricter control of and more restricted access to the herb.
Author and Article Information
From San Francisco Bay Area Regional Poison Control Center and University of California, San Francisco, San Francisco, California; Institute of Forensic Sciences Toxicology Laboratory, Oakland, California; and University of Washington School of Pharmacy, Seattle, Washington.
ARTICLE
Pennyroyal Toxicity: Measurement of Toxic Metabolite Levels in Two Cases and Review of the Literature
Acknowledgments: The authors thank Koorosh Shariat, MD, for referring case 1.
Grant Support: By National Institutes of Health Program Project grant GM32165 and, in part, by National Institutes of Health grant GM25418. Human liver microsomes were obtained from the University of Washington, School of Pharmacy, Human Liver Bank.
Requests for Reprints: Ilene B. Anderson, PharmD, San Francisco Bay Area Regional Poison Control Center, San Francisco General Hospital, Room 1E86, 1001 Potrero Avenue, San Francisco, CA 94110.
Current Author Addresses: Drs. Anderson and Mullen: San Francisco Bay Area Regional Poison Control Center, San Francisco General Hospital, Room 1E86, 1001 Potrero Avenue, San Francisco, CA 94110.
This article has been cited by other articles:
|
|
 |
|
  S. Gabardi, K. Munz, and C. Ulbricht A Review of Dietary Supplement-Induced Renal Dysfunction Clin. J. Am. Soc. Nephrol., July 1, 2007; 2(4): 757 - 765. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Hanje, B. Fortune, M. Song, D. Hill, and C. McClain The Use of Selected Nutrition Supplements and Complementary and Alternative Medicine in Liver Disease Nutr Clin Pract, June 1, 2006; 21(3): 255 - 272. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Smolinske Herbal Product Contamination and Toxicity Journal of Pharmacy Practice, June 1, 2005; 18(3): 188 - 208. [Abstract] [PDF]
|
|
|
|
 |
|
 S. D. Nelson and W. F. Trager THE USE OF DEUTERIUM ISOTOPE EFFECTS TO PROBE THE ACTIVE SITE PROPERTIES, MECHANISM OF CYTOCHROME P450-CATALYZED REACTIONS, AND MECHANISMS OF METABOLICALLY DEPENDENT TOXICITY Drug Metab. Dispos., December 1, 2003; 31(12): 1481 - 1497. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-J. Chen, E. H. Lebetkin, and L. T. Burka METABOLISM OF (R)-(+)-MENTHOFURAN IN FISCHER-344 RATS: IDENTIFICATION OF SULFONIC ACID METABOLITES Drug Metab. Dispos., October 1, 2003; 31(10): 1208 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-J. Chen, E. H. Lebetkin, and L. T. Burka COMPARATIVE DISPOSITION OF (R)-(+)-PULEGONE IN B6C3F1 MICE AND F344 RATS Drug Metab. Dispos., July 1, 2003; 31(7): 892 - 899. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D. Woolf Herbal Remedies and Children: Do They Work? Are They Harmful? Pediatrics, July 1, 2003; 112(1): 240 - 246. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A Frenkel and J. M Borkan An approach for integrating complementary- alternative medicine into primary care Fam. Pract., June 1, 2003; 20(3): 324 - 332. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Ernst Herbal Medicines for Children Clinical Pediatrics, April 1, 2003; 42(3): 193 - 196. [PDF]
|
|
|
|
|
|
L.-J. Chen, E. H. Lebetkin, and L. T. Burka Metabolism of (R)-(+)-Pulegone in F344 Rats Drug Metab. Dispos., December 1, 2001; 29(12): 1567 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. d. Pribitkin and G. Boger Herbal Therapy: What Every Facial Plastic Surgeon Must Know Arch Facial Plast Surg, April 1, 2001; 3(2): 127 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Miyazawa, M. Shindo, and T. Shimada Oxidation of 1,8-Cineole, the Monoterpene Cyclic Ether Originated From Eucalyptus Polybractea, by Cytochrome P450 3A Enzymes in Rat and Human Liver Microsomes Drug Metab. Dispos., February 1, 2001; 29(2): 200 - 205. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Vanholder, R. De Smet, and G. Lesaffer p-Cresol: a toxin revealing many neglected but relevant aspects of uraemic toxicity Nephrol. Dial. Transplant., December 1, 1999; 14(12): 2813 - 2815. [Full Text] [PDF]
|
|
|
|
 |
|
 R. VANHOLDER and R. DE SMET Pathophysiologic Effects of Uremic Retention Solutes J. Am. Soc. Nephrol., August 1, 1999; 10(8): 1815 - 1823. [Full Text]
|
|
|
|
|
|
S. C. Khojasteh-Bakht, W. Chen, L. L. Koenigs, R. M. Peter, and S. D. Nelson Metabolism of (R)-(+)-Pulegone and (R)-(+)-Menthofuran by Human Liver Cytochrome P-450s: Evidence for Formation of a Furan Epoxide Drug Metab. Dispos., May 1, 1999; 27(5): 574 - 580. [Abstract] [Full Text]
|
|
|
|
 |
|
 O. Y. Oumeish The Philosophical, Cultural, and Historical Aspects of Complementary, Alternative, Unconventional, and Integrative Medicine in the Old World Arch Dermatol, November 1, 1998; 134(11): 1373 - 1386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. C. Khojasteh-Bakht, L. L. Koenigs, R. M. Peter, W. F. Trager, and S. D. Nelson (R)-(+)-Menthofuran Is a Potent, Mechanism-Based Inactivator of Human Liver Cytochrome P450 2A6 Drug Metab. Dispos., July 1, 1998; 26(7): 701 - 704. [Abstract] [Full Text]
|
|
|
|
 |
|
 Don't Use Pennyroyal Journal Watch Women's Health, May 1, 1996; 1996(501): 18 - 18. [Full Text]
|
|
Article
