Sheep copper poisoning

In mammals, phenobarbital and phenytoin increase serum ceruloplasmin concentrations (Aaseth and Norseth 1986). Chronic copper poisoning in sheep is exacerbated when diets contain heliotrope plants (Heliotropium sp., Echium spp., Senecio sp.). Aggravated effects of the heliotrope plants include reduced survival and a twofold to threefold increase in liver and kidney copper concentrations when compared to control animals fed copper without heliotropes (Howell et al. 1991). Rats given acutely toxic doses of 2,3,7,8-tetrachlorodibenzo-para-dioxin had elevated concentrations of copper in liver and kidney because of impaired biliary excretion of copper (Elsenhans et al. 1991). Morphine increases copper concentrations in the central nervous system of rats, and dithiocarbam-ates inhibit biliary excretion (Aaseth and Norseth 1986). In human patients, urinary excretion of copper is increased after treatment with D-penicillamine, calcium disodium EDTA, or calcium trisodium diethylenetriamine penta acetic acid (Flora 1991). 

Domestic sheep, Ovis aries Copper-poisoned vs. normal sheep ... 

Chronic copper poisoning in domestic sheep is first characterized by a period of passive accumulation of copper in the tissues. This period varies from a few weeks to more than a year. During this time the animal appears outwardly normal although the liver may contain more than 1000 mg Cu/kg DW and plasma activities of aspartate transaminase, sorbitol dehydrogenase, lactic... 

MacPherson, A. and R.G. Hemingway. 1969. The relative merit of various blood analyses and liver function tests in giving an early diagnosis of chronic copper poisoning in sheep. Brit. Veterin. Jour. 125 213-221. 

Thompson, R.H. and J.R. Todd. 1974. Muscle damage in chronic copper poisoning of sheep. Res. Veterin. Sci. 16 97-99. 

Froslie, A., G. Norheim, and N.E. Soli. 1983. Levels of copper, molybdenum, zinc, and sulphur in concentrates and mineral feeding stuffs in relation to chronic copper poisoning in sheep in Norway. ActaAgric. Scand. 33 261-267. 

Sheep are more susceptible to copper poisoning than are cattle, but cattle are more sensitive to molybdenum poisoning than are sheep. The in vivo relationship between copper and molybdenum is well understood. Excess copper induces molybdenum deficiency and vice versa. The most frequent cause of copper poisoning in sheep is by uninformed farmers feeding cattle feed to sheep. Copper from different sources is additive. Copper is an essential element for cattle and is usually added to their feeds however, molybdenum is not considered essential and is therefore not added. Cattle feeds therefore have high copper concentrations and no molybdenum feeding this ration to sheep upsets the normal 6 1 copper molyb-denum ratio in vivo. 

The specific treatment of WD is aimed at removing excessive body copper by chelation with D-penicillamine. Chelation therapy will reverse most of the clinical disturbances in the symptomatic WD patient, and will maintain nonsymptomatic WD patients in that state for their life-span (Marsden 1984, Mowet 1984). Patients who develop intolerance to D-penicillamine may be treated with equal success with Tri-entine (triethylene tetramine dihydrochloride) (Scheinberg 1991). Continuous oral zinc acetate therapy may also reduce the amount of excessive copper in the bloodstream (Brewer et al. 1983, Cossack 1987), but conclusive clinical tests on such a therapy have yet to be performed. Tetrathiomo-lybdate was successfully used to remove excessive copper in copper-poisoned sheep (Wing and Mehra 1990), and some clinical trials are currently in progress to ascertain the value of molybdenum in human WD therapy. It is pertinent to note here that in a case report on high molybdenum intake from a dietary supplement, an acute psychotic clinical picture was observed (Momci-lovic 1999). 

Metal metabolism The use of zinc in the treatment of copper deposition due to Wilson s disease was first proposed in the Netherlands by Schouwink in his 1961 PhD thesis [107, 108 ]. This was based on earher experience in veterinary medicine in Australia that zinc salts are effective in copper poisoning in sheep. Later observations showed that stimulation by zinc of metallothionein blocks the intestinal absorption of copper. Metallothionein binds both zinc and copper, but it has a higher affinity for the latter. It binds newly absorbed copper in enterocytes and prevents it from passing firom the gut into the circulation. Copper has no enterohepatic circulation, and Ihe shedding of enterocytes with copper still bound to metallothionein results in higher fecal copper excretion. 

---