ASPECT OF THE METABOLISM OF CYANIDE IN THE RAT
ASPECT OF THE METABOLISM OF CYANIDE IN THE RAT
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Date
1978-09
Authors
OKOH, PATRICK NWANZB
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Abstract
The use of inorganic cyanide for cyanide metabolism studies
in animals has the advantage that the cyanide administered is fully
available as opposed to cyanogenic glycosides in which the cyanide
radical is not completely liberated in the animal body.
However, when KCN was added to the diet which had been
moistened with water, it was lost by transformation to other products,
and perhaps also as volatile HCN. A preliminary study revealed that
formate is one of the products formed. A method was developed for
the addition of KCN to the normal rat diet, in which no significant
loss or transformation of the added substance occurred.By this
method it was possible to compare tho relative toxicities of KCN
and vitamins A and D when mixed in the diet, as measured by weight gain
in growing rats. KCN given to groups of rats at a dose level of
77 umoles/rat/day in the diet did not diminish weight gain whereas
vitamins A (38•5 umoles/rat/day) or D, (0.55 umoles/rat/day)
significantly diminished weight gain in rowing rats.
A study of tho metabolism of " C-labelled cyanide was carried
out in the rat exposed to semi-continuous intake of KCN in the diet
for throe weeks. The pattern of excretion and tissue levels of" C
activity was similar after subcutaneous or intraperitoneal injections
and oral administration of Na1kCN. After intraperitoneal and subcutaneous
injections of Na"CN, 2k of dosed activity was excreted in the urine
within 9h of which 71% was in the form of thiocyanate. The
corresponding value after 9h in the faeces was 0.5. • About 4.3 of
the injected activity appeared in the respiratory air of which 85 was
present as CO and only 15 as cyanide.
All tissues contained radioactivity 9h after the Na"CN
administration but very high amounts were found in the gastrointestinal
tract, particularly in the stomach, which accounted for
18% of the total dosed activity. Moat of this was in the contents
of the stomach, of which over 80% was in the form of thiocyanate.
When a small amount of KS11CN was given by mouth to the rat
with elevated plasma ScN level, most of the activity waa excreted
in the urine (mainly as SCN) and only small amounts were found in
the faeces. This indicated that the thiooyanate secreted into the
stomach contents of the rat was largely reabsorbed by the intestine
into the body fluid, to be partly excreted in the urine and partly
resecreted into the gastric juice.
The time of initial secretion of thiocyanate into the rat
stomach contents after subcutaneous injection of cyanide was calculated
to bo 7 min, while the rate of secretion was estimated to be 0.31 of
the administered dose per minute
Description
A Thesis
Submitted in accordance with the
requirements of the
UNIVERSITY OF LIVERPOOL
for the degree of
DOCTOR IN PHILOSOPHY
September, 1978
Keywords
ASPECT,, METABOLISM,, CYANIDE,, RAT,