Methods for reducing Pimelea poisoning of cattle

Poisoning of cattle by plants of the Pimelea species incurs heavy losses to individual producers in regions of South West Queensland, North Western New South Wales, South Australia, and the Northern Territory. Due to the vast

areas of affected land, control of the plant is perceived as non -viable. Therefore, the aim of this study has been to contribute to the development of methods to reduce the losses caused by the condition from an animal health

perspective.

Immunisation with conjugates of a purified mixture of Pimelea toxins and ovalbumin with varying inclusion ratios has resulted in the production of bovine serum IgG antibodies, which attenuate the effect of purified Pimelea

toxins on bovine pulmonary venule preparations in vitro. Cattle immunised with a vaccine batched from two conjugates from experimental studies have been shown to develop toxin specific antibody responses while affected and unaffected by poisoning at the time of immunisation. Experiments to evaluate the protective attributes of the vaccine under field conditions have produced consistent, yet non -significant results regarding liveweight and condition

scores of vaccinated animals. Therefore, no immediate conclusions can be drawn regarding the protective properties of the experimental vaccine without futrther investigation.

Investigation of a structure -activity relationship of the Pimelea toxins has resulted in new knowledge regarding key functional requirements for binding to and activation of protein kinase C (PKC). A structural variant of simplexin

was found not to activate PKC in vitro, therefore the conversion of simplexin to this compound in the rumen of cattle would provide a means of reducing the impact caused by Pimelea poisoning. It was found that hydroxyl groups at the 4- and 5- positions of simplexin were essential for PKC binding. Carbonyl functionality at position 3- of simplexin, although significant for PKC binding, was shown to be more related to the activation properties of the resulting complex. The alteration of hydroxyl functionality at the 20- position of

mezerein (a selected reference compound) was shown not to significantly alter binding, however no conclusion can be drawn regarding the importance of this functionality of simplexin.

Derivatisation of Pimelea toxin for assay by gas chromatography (GC) and high performance liquid chromatography (HPLC) was found not to be feasible.