Hepatotoxicity of pulegone in rats: Its effects on microsomal enzymes, in vivo

Moorthy, Bhagavatula; Madyastha, Prema; Madyastha, K. M.

doi:10.1016/0300-483x(89)90022-x

Cited by 46 publications

(17 citation statements)

References 22 publications

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“…Unfortunately, widescale application of pulegone would be impossible because of its toxic properties. A number of large studies have shown that pulegone and its main metabolite, menthofuran, show hepato-and neurotoxicity as well as pulmonary toxicity toward vertebrates (Gordon et al 1982, Olsen and Thorup 1984, Moorthy et al 1989). …”

mentioning

confidence: 99%

Feeding Deterrent Activity of Terpenoid Lactones with the <I>p</I>-Menthane System Against the Colorado Potato Beetle (Coleoptera: Chrysomelidae)

Szczepanik

Dams

Wawrzeńczyk

2005

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mentioning

confidence: 99%

Feeding Deterrent Activity of Terpenoid Lactones with the <I>p</I>-Menthane System Against the Colorado Potato Beetle (Coleoptera: Chrysomelidae)

Szczepanik

Dams

Wawrzeńczyk

2005

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“…Hepatotoxic doses of pulegone, five daily doses of 400 mg/kg, decreased the amount of hepatic cytochromes P450 in rats based on total cytochrome P450 content and N-demethylase activity with a general substrate, aminopyrine. These parameters were also decreased following single doses of 200 but not 100 mg/kg (Moorthy et al, 1989). In the pretreatment study, distribution of a radiolabeled pulegone dose of 80 mg/kg following three daily 80 mg/kg doses of unlabeled pulegone showed some subtle differences from a single dose in naive animals.…”

Section: Disposition Of Pulegone In Mice and Ratsmentioning

confidence: 85%

“…It appears that changes in oxidase activity induced by relatively nontoxic doses of pulegone are minor, and those that have been observed may be more a result of hepatotoxicity. For example, Moorthy et al (1989) report an LD 50 of 245 mg/kg; they report decreases in enzymatic activity beginning at 200 mg/kg.…”

Section: Disposition Of Pulegone In Mice and Ratsmentioning

confidence: 99%

COMPARATIVE DISPOSITION OF (R)-(+)-PULEGONE IN B6C3F1 MICE AND F344 RATS

Chen¹,

Lebetkin²,

Burka³

2003

Drug Metab Dispos

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This article is available online at http://dmd.aspetjournals.org ABSTRACT:Pulegone is a monoterpene ketone that is usually associated with the herb pennyroyal but is also found in the essential oils from many other mint species. It is the major constituent of pennyroyal oil. Pennyroyal is used as a flavoring and fragrance and as an herbal medicine to induce menstruation and abortion. A disposition study of 14 C-pulegone in B6C3F1 mice and F344 rats has been conducted at doses from 0.8 to 80 mg/kg. Mice excrete 85 to100% of the dose in 24 h. Rats excrete only 59 to 81% of the administered radioactivity in the same time, primarily in urine and feces, with a trace in respired air. Consequently, tissue concentrations are lower in mice than in rats. Male rats tend to have higher tissue concentrations, especially in kidney, than female rats have, but this sex difference is not seen in mice. The residual radioactivity at 24 h demonstrates potential for accumulation of pulegone-derived material in several tissues following multiple doses. The metabolic profile is complex in both species, with at least three pathways involving hydroxylation, reduction, or conjugation with glutathione as first steps. Mercapturic acid pathway metabolites were detected in bile in mice and both bile and urine in rats.

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“…With regard to the former, the clinical cases of patients who ingested a large amount of pennyroyal oil resulted in hepatic toxicity that, upon further investigation, was classified as hepatic centrilobular necrosis. In mice and rats, intraperitoneal (ip) administration of pennyroyal oil resulted in dosedependent hepatotoxicity similar to that observed in human, and, thus, mouse and rat were determined to be appropriate hepatotoxicity models (Gordon et al, 1982;Mizutani et al, 1987;Moorthy et al, 1989a;Thomassen et al, 1988). The markers used for liver damage were plasma glutamic pyruvic transaminase (GPT) and glutathione (GSH).…”

Section: Determination Of Animal Models For and Toxins In Pennyroyal Oilmentioning

confidence: 93%

A decades-long investigation of acute metabolism-based hepatotoxicity by herbal constituents: a case study of pennyroyal oil

Gordon

Khojasteh²

2014

Drug Metabolism Reviews

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Herbal supplements are often regarded as "natural", and are, therefore, considered by many to be safer than pharmaceuticals; however, the adverse effects of these supplements are under-reported in many cases. Many herbal supplements, such as pyrrolizidine alkaloids, kava, chaparral and germander, are known to induce liver injury, which, in general, is one of the main toxicity liabilities observed in the clinic and accounts for about half of total liver failures. One example is the hepatotoxicity of pennyroyal oil, which is ingested as an abortifacient, among other uses. For three decades, the late Professor Sidney Nelson contributed to our understanding of the mechanism of toxicity of pennyroyal and broadened our understanding of chemical toxicology. Here we present the studies and review the findings on acute hepatotoxicity of pennyroyal oil. These studies involved the isolation and characterization of pennyroyal components, determination of the appropriate animal models, identification of the structural requirement for toxicity and determination of the target enzymes and the enzymes involved in the process of bioactivation. Studies with stable isotope labeled pennyroyal metabolites, pulegone and menthofuran, furthered our understanding of the role of cytochrome P450 in the oxidation of these compounds. This review presents the investigational tools used in the study of pennyroyal oil, allowing the reader to not only appreciate these methods but also utilize them to tackle and better understand metabolism-based toxicity in their own projects.

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Hepatotoxicity of pulegone in rats: Its effects on microsomal enzymes, in vivo

Cited by 46 publications

References 22 publications

Feeding Deterrent Activity of Terpenoid Lactones with the <I>p</I>-Menthane System Against the Colorado Potato Beetle (Coleoptera: Chrysomelidae)

Feeding Deterrent Activity of Terpenoid Lactones with the <I>p</I>-Menthane System Against the Colorado Potato Beetle (Coleoptera: Chrysomelidae)

COMPARATIVE DISPOSITION OF (R)-(+)-PULEGONE IN B6C3F1 MICE AND F344 RATS

A decades-long investigation of acute metabolism-based hepatotoxicity by herbal constituents: a case study of pennyroyal oil

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