| dc.description.abstract | Copper poisoning was produced in sheep by feeding them
copper sulfate (CuS04·5H20). In sheep given daily oral doses
of 1.5 g CuS04'SH20 as 1 percent solution, severe signs of
hemolysis appeared in 24 to 26 days. Signs of hemoglobinuria,
hemoglobinemia and jaundice were accompanied by a rapid drop
in hematocrit to a low of 6 percent in four days. This disease
was subsequently called subacute copper poisoning.
Sheep fed copper sulfate as a powder added to the ration
hemolyzed after day 42. The hemolytic crises were mild and
some sheep went through two crises before they were killed.
One sheep was fed copper for 131 days without signs of a
crisis. This regimen was referred to as chronic copper poisoning.
Aspects of chronic copper poisoning studied included
plasma assays for liver and kidney function, total plasma
copper concentration and ceruloplasmin activity. Histological
changes in the liver and kidney were examined at postmortem.
Erythrocyte (RBC) pentose phosphate shunt pathway
e~zymcs and other Jlematologic parameters were recorded. RBC
morphology was studied using scanning electron microscopy.
Subcellular liver copper storage was determined by
differential centrifugation of post-mortem liver homogenate
and examination of glutaraldehyde fixed liver samples using
transmission electron microscopy.
Increased activities of plasma glutamate oxaloacetate
transaminase (GOT), sorbitol dehydrogenase (SDH) , lactate
dehydrogenase (LDH) and sulfobromophthalein (BSP) clearance
time during the hemolytic crisis implied destruction of liver
tissue which was confirmed by histology. Increase in liver
function tests prior to hemolytic crisis was noted in the subacutely
poisoned sheep and in one of the five sheep that were
chronically poisoned. A similar trend was noted in plasma
copper concentration. Plasma ceruloplasmin activity did not
change. Liver function tests and plasma copper for early
diagnosis of chronic copper poisoning may be of use in animals
which would later undergo severe crises.
Increases in plasma blood urea nitrogen (BUN) and creatinine
have a prognostic importance in hemolytic crisis.
Erythrocyte glucose-6-phosphate dehydrogenase (G6PD),
glutathione reductase (GR) and glutathione peroxidase (GSH-Px)
remained unaffected until after the hemolytic crisis when
their activities increased due to an increase in circulating
immature erythrocytes. Erythrocyte reduced glutathione (GSH)
decreased by nearly SO percent during crisis. Decrease of
GSH was not attributable to in vivo inhibition of pentose
phosphate shunt enzymes.
Scanning electron microscopy revealed that erythrocytes
retained a normal biconcave shape up to 48 hOUTS before hemolytic
crisis. Changes observed on the day preceeding the
crisis incJ.uded irregularly distributed swellings attributed
to Heinz bodies, fragmentation of the erythrocyte membrane and
spicule formation in a few cells. Hemolytic crisis was associated
with marked distortion and rounding due to increased
fragmentation. Many cells contained pits where Heinz bodies
had been located previously.
Sheep with normal liver copper concentrations stored
nearly 40 percent in the 14,000 g pellet. In chronically
poisoned sheep, over 40 percent of liver copper appeared in
the nuclear fraction (600 g pellet), while subacutely poisoned
sheep accumulated copper mostly in the cytosol.
Liver cytosol of sheep with normal or slightly elevated
copper concentr~tion had most copper in a high molecular
weight (MW) fraction (75,000) while a low molecular weight
fraction (12,000) showed increased binding in copper poisoned
sheep. A fourth copper fraction (MW approximately 5000) was
recorded in copper po~soned sheep. This fraction bound the
most copper in subacutely poisoned sheep and may be related
to appearance and severity of hemolytic crisis signs.
D-penicillamine, 0.5 g as a 2 percent solution given
daily as an intravenous (rV) injection for four days, did not
significantly lower hepatic copper content in housed South-
Jown sheep. A mean of 3.8 mg copper was mobilized through the
urine in four days. The IV treatment did not affect the health of the sheep. | en |
