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Studies of the pathogenesis, toxicology and pathology of lupinosis and associated conditions

Allen, Jeremy George (1989) Studies of the pathogenesis, toxicology and pathology of lupinosis and associated conditions. PhD thesis, Murdoch University.

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Abstract

Lupinosis is caused by phomopsins, which are toxic metabolites of the fungus Phomopsis leptostromiformis. This thesis records a series of studies of aspects of the pathogenesis, toxicology and pathology of lupinosis and associated conditions.

A sheep bioassay developed for the estimation of phomopsins-associated toxicity in feed samples infected with Phomopsis leptostromiformis is described. Toxicity ratings provided by this bioassay were compared with results provided by a nursling rat bioassay and a chemical assay for phomopsin A. There was a poor correlation between the results from the two bioassays, but results from the sheep bioassay correlated well with those from the chemical assay.

The procedure for scoring microscopic liver damage in the sheep bioassay was modified to enable assessment of the severity of lupinosis in sheep grazing toxic lupin stubbles for various periods. Individual sheep were awarded liver injury scores as a measure of the severity of their lupinosis. The microscopic changes assessed had a dynamic interrelationship with each other, and with other parameters including the daily intake of phomopsins and the period over which they were consumed. For this reason liver injury scores could only be used to compare the severity of lupinosis in sheep in individual experiments, and at the same times during experiments. Nevertheless, liver injury scores proved to be a valuable experimental tool and were used in several of the investigations reported in this thesis.

The roles of copper and the hepatic microsomal enzymes in the pathogenesis of lupinosis were examined. It was established that copper accumulates in the liver of sheep with subacute and chronic lupinosis. The concentration of copper in the liver was positively correlated with the degree of liver injury. It was also found that the degree of liver injury was correlated positively with the concentration of selenium and negatively with the concentration of zinc.

Induction of the hepatic microsomal enzymes with DDT and phenobarbitone, and inhibition with SKF 525A and carbon disulphide, did not alter the toxicity of phomopsin A in rats. However, the toxicity in both males and females was significantly increased when hepatic microsomal enzymes were inhibited by adrenalectomy, and was significantly increased in males only when they were inhibited by cobalt chloride.

Toxicological studies established 50% lethal doses for phomopsin A in sheep and pigs following a single subcutaneous administration, and in sheep following a single oral administration and daily oral administrations. Sheep were approximately 40 times more susceptible than pigs to phomopsin A, and in sheep phomopsin A was approximately 65 times more toxic following a single subcutaneous injection rather than a single oral administration.

It was demonstrated that only the Biotype A strains of P. leptostromiformis were toxicogenic when grown on autoclaved wheat. The different strains of this biotype had varying potentials to produce phomopsin A. Evidence for a toxic phomopsin additional to phomopsins A and B is presented, and it was referred to as phomopsin C.

Aspects of the pathology, clinical chemistry and haematology of experimental phomopsins toxicosis in sheep and rats, which complemented or differed from previous descriptions, are reported. Special attention was given to lupinosis-associated spongy degeneration of the brain and lupinosis-associated myopathy in sheep. Specific experiments conducted to study the pathogenesis and pathology of these conditions are documented.

Item Type: Thesis (PhD)
Murdoch Affiliation: School of Veterinary Studies
Notes: Note to the author: If you would like to make your thesis openly available on Murdoch University Library's Research Repository, please contact: repository@murdoch.edu.au. Thank you.
Supervisor(s): Huxtable, Clive
URI: http://researchrepository.murdoch.edu.au/id/eprint/53693
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