This article is inspired by a tweet this week by Hannah Bannister @HannahBannist_r

 

Hannah tweets “Brushtail possums have significantly declined over the past 200 years” (in Australia).

 

The common brush-tailed possum (Trichosurus vulpecula) is a fascinating species. This species is quite prevalent in Sydney and is probably considered an annoyance to many Sydney-siders. The common-ringed tail possum (Pseudocheirus peregrinus) is also found in some parts of Sydney.

The common ring-tailed possum has a selective diet that primarily comprises of Eucalyptus leaves however the common brush-tailed (CB-T) possum not only eats Eucalyptus leaves but also eats flowers, fruit and seeds and is also known to eat small birds (McDowell & McLeod 2007).

Because both of these species are found around Sydney, (our laboratory is at The University of Sydney), thanks to our colleague Dr Derek Spielman, we were able to opportunistically obtain liver tissue from both species of possums that had been euthanased due to being the victims of dog attacks or hit by cars.

 

We compared the rate of metabolism of the non-steroidal anti-inflammatory medicine meloxicam between both possum species, the koala, rat and dog and found that the C-BT possum metabolised the non-steroidal anti-inflammatory drug more rapidly than any other species as demonstrated in the figure below.

meloxicam-depletion-from-benjamins-thesis

Figure 1. Rate of in vitro meloxicam depletion concentration (expressed as log substrate remaining) vs. incubation time. The rate of depletion of meloxicam (as a steeper gradient) is greater in the common brush-tailed possum, followed by the koala, the common ring-tailed possum and then the rat (Kimble et al. 2014).

 

 

This observation surprised us and we became very interested in what was known about the CB-T possum’s fast metabolic pathways: The common brush-tailed possum was deliberately introduced into New Zealand during the mid-1800s for its fur, but is now considered a significant vertebrate pest and vector for bovine tuberculosis (McDowell & McLeod 2007). In order to find a toxin to reduce numbers, this species has been shown to be relatively resistant to toxins. This species can tolerate higher doses of some medicines to kill internal parasites (Ralson et al. 2001) and paracetamol (Eason et al. 1998) which may be attributable to their rapid metabolism pathways. Some of these pathways also appear to undergo adaptation to deal with higher toxin concentrations encountered in their diet, as this species and other indigenous marsupials in Western Australia have developed tolerance to the fluoroacetate, a.k.a. 1080 toxin (King et al. 1978) and the terpenoid 1,8-cineole (McLean & Foley 1997).

 

So what is the relevance to our research? We are working on using liver tissue to look at metabolism rates of medicines in selected Australian animals. This is so that we can work out better dose rates for those medicines that undergo metabolism and not need to use the live animal. Because of the superior activity of the C-BT tissue, this species acts as a wonderful positive control because of the rapid rate of metabolism…. If the CB-T tissue metabolises the medicine, this is good evidence that the assay is working then we also conduct the same assay in other species.

 

Who knew that the CB-T  would provide valuable tissue that acts as a useful positive control for in vitro metabolism studies?

 

References

Eason C, Wright G, Gooneratne R (1998) Pharmacokinetics of antipyrine, warfarin and paracetamol in the brushtail possum. Journal of Applied Toxicology, 19, 157-161.

Kimble B, Li KM, Valtchev P, Higgins DP, Krockenberger MB, Govendir M (2014) In vitro metabolism of meloxicam in koalas (Phascolarctos cinereus), brushtail possums (Trichosurus vulpecula), ringtail possums (Pseudocheirus peregrinus), rats and dogs. Comparative Biochemistry and Physiology. Part C, Pharmacology, Toxicology and Endocrinology, 161, 7-17.

King D, Oliver A, Mead R (1978) The adaptation of some Western Australian mammals to food plants containing fluoroacetate. Australian Journal of Zoology, 26, 699-712.

McDowell A, McLeod BJ (2007) Physiology and pharmacology of the brushtail possum gastrointestinal tract: relationship to the human gastrointestinal tract. Advanced Drug Delivery Reviews, 59, 1121-1132.

McLean SR, Foley WF (1997) Metabolism of Eucalyptus terpenes by herbivorous marsupials. Drug Metabolism Reviews, 29, 213-218.

Ralson MJ, Stankiewicz M, Heath DD (2001) Anthelmintics for the control of nematode infections in the brushtail possum (Trichosurus vulpecula). New Zealand Veterinary Journal, 49, 73-77.