In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (<em>Trichosurus vulpecula</em>) and Rodents
Folivore marsupials, such as brushtail possum (<i>Trichosurus Vulpecula</i>) and koala (<i>Phascolarctos cinereus</i>), can metabolise higher levels of dietary terpenes, such as cineole, that are toxic to eutherian mammals. While the highly efficient drug metabolising enzymes...
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MDPI AG
2021-12-01
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| author | Ravneel R. Chand Mhairi Nimick Belinda Cridge Rhonda J. Rosengren |
| author_facet | Ravneel R. Chand Mhairi Nimick Belinda Cridge Rhonda J. Rosengren |
| author_sort | Ravneel R. Chand |
| collection | DOAJ |
| description | Folivore marsupials, such as brushtail possum (<i>Trichosurus Vulpecula</i>) and koala (<i>Phascolarctos cinereus</i>), can metabolise higher levels of dietary terpenes, such as cineole, that are toxic to eutherian mammals. While the highly efficient drug metabolising enzymes, cytochrome P450 3A (CYP3A) and phase II conjugating enzymes (UDP-glucuronosyltransferase, UGT), are involved in the metabolism of high levels of dietary terpenes, evidence for inhibitory actions on these enzymes by these terpenes is scant. Thus, this study investigated the effect of cineole and its derivatives on catalytic activities of hepatic CYP3A and UGT in mice, rats, and possums. Results showed that cineole (up to 50 µM) and its derivatives (up to 25 µM) did not significantly inhibit CYP3A and UGT activities in mice, rats, and possums (both in silico and in vitro). Interestingly, basal hepatic CYP3A catalytic activity in the possums was ~20% lower than that in rats and mice. In contrast, possums had ~2-fold higher UGT catalytic activity when compared to mice and rats. Thus, these basal enzymatic differences may be further exploited in future pest management strategies. |
| first_indexed | 2024-03-10T04:33:59Z |
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| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T04:33:59Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
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| spelling | doaj.art-b66688e6aa8b45f69af43c9793cbb1b22023-11-23T03:54:22ZengMDPI AGBiology2079-77372021-12-011012132610.3390/biology10121326In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (<em>Trichosurus vulpecula</em>) and RodentsRavneel R. Chand0Mhairi Nimick1Belinda Cridge2Rhonda J. Rosengren3Department of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago, Dunedin 9016, New ZealandDepartment of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago, Dunedin 9016, New ZealandScience for Communities, Christchurch Science Centre, Christchurch 8041, New ZealandDepartment of Pharmacology and Toxicology, School of Biomedical Sciences, University of Otago, Dunedin 9016, New ZealandFolivore marsupials, such as brushtail possum (<i>Trichosurus Vulpecula</i>) and koala (<i>Phascolarctos cinereus</i>), can metabolise higher levels of dietary terpenes, such as cineole, that are toxic to eutherian mammals. While the highly efficient drug metabolising enzymes, cytochrome P450 3A (CYP3A) and phase II conjugating enzymes (UDP-glucuronosyltransferase, UGT), are involved in the metabolism of high levels of dietary terpenes, evidence for inhibitory actions on these enzymes by these terpenes is scant. Thus, this study investigated the effect of cineole and its derivatives on catalytic activities of hepatic CYP3A and UGT in mice, rats, and possums. Results showed that cineole (up to 50 µM) and its derivatives (up to 25 µM) did not significantly inhibit CYP3A and UGT activities in mice, rats, and possums (both in silico and in vitro). Interestingly, basal hepatic CYP3A catalytic activity in the possums was ~20% lower than that in rats and mice. In contrast, possums had ~2-fold higher UGT catalytic activity when compared to mice and rats. Thus, these basal enzymatic differences may be further exploited in future pest management strategies.https://www.mdpi.com/2079-7737/10/12/1326cineole and derivativesbrushtail possumrodentsCYP3AUGT |
| spellingShingle | Ravneel R. Chand Mhairi Nimick Belinda Cridge Rhonda J. Rosengren In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (<em>Trichosurus vulpecula</em>) and Rodents Biology cineole and derivatives brushtail possum rodents CYP3A UGT |
| title | In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (<em>Trichosurus vulpecula</em>) and Rodents |
| title_full | In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (<em>Trichosurus vulpecula</em>) and Rodents |
| title_fullStr | In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (<em>Trichosurus vulpecula</em>) and Rodents |
| title_full_unstemmed | In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (<em>Trichosurus vulpecula</em>) and Rodents |
| title_short | In Vitro Hepatic Assessment of Cineole and Its Derivatives in Common Brushtail Possums (<em>Trichosurus vulpecula</em>) and Rodents |
| title_sort | in vitro hepatic assessment of cineole and its derivatives in common brushtail possums em trichosurus vulpecula em and rodents |
| topic | cineole and derivatives brushtail possum rodents CYP3A UGT |
| url | https://www.mdpi.com/2079-7737/10/12/1326 |
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