Folivore marsupials, such as brushtail possum (Trichosurus Vulpecula) and koala (Phascolarctos cinereus), 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.
Worldwide, introduced pest species create significant challenges to native biodiversity and individual health. New Zealand has an extensive history of attempting to protect biodiversity from introduced pests such as the Brushtail possum (Trichosurus vulpecula [Diprotodontia: Phalangeridae]). Success has been achieved on a small scale, but the transition to the whole country management poses new issues. Therefore, this review uses the framework of ‘Predator Free 2050’ to summarize current practices and scrutinize new technologies. Importantly, we include a toxicology focus to the discussion, providing detail on the mechanism(s) of action that inform decisions regarding the pros and cons for the use of various chemical agents. Currently, the New Zealand government supports the use of sodium fluoroacetate (1080) for predator control on a mass scale, but this comes with a social opposition that is not always reflective of the underlying science. Understanding this controversy is vital if new strategies are to be deployed to achieve large-scale pest management. We use New Zealand as a case study in this area because its unique and isolated ecosystem provides a global opportunity for understanding new technologies and best practice.
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