الفهرس 
Dosage and duration of administration:
PATHOLOGICAL CHANGES Opiate (morphine-codeine-pethidine)Only 14 pages are availabe for public view
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Abstract
In the present Investigation, 480 apparently healthy mature rats of both sexes weighting
125-150 gm were chosen and divided 1nto seven groups, each with subgroups Twelve rats were
used for each group or subgroup.
At the end of each experimental group, blood samples were obtained from the rats for
biochemical analysis, the rats were then sacrificed for histopathological examination.
The results in the present study showed:
1- No significant biochemical or histopathological changes in group II (positive control as
placebo) after i.p. injection of suspension of 5% gum acacia in distilled water.
2- i.p. injection of 20 mg/100 g rats’ body weight xanthinol nicotinate
alone (group VII) caused no significant changes in biochemical and
histopathological examination when compared with both negative and positive control groups
(Placebo).
3- Morphine sulphate 5.98 mg/100 g body weight s.c. injection (group Ill,) showed significant
elevation of liver enzymes (ALT, AST and ALP) and decrease of total proteins and
albumin. Also caused significant elevation of kidney function tests (BUN and
creatinine). These changes were accompanied by histopathological changes detected in the
liver as dilated and congested central vein, portal tract inflammation and focal
piece meal necrosis. Kidney showed hypercellular congested glomeruli and cloudy
swelling of proximal convoluted tubules and vaculation of lining epithelium of distal
convoluted tubules. Heart after morphine injection revealed congestion and focal mononuclear
inflammatory cell infiltrate. While histopathological examination of brain showed congestion.
4- Codeine phosphate 7.3 mg/100 g body weight rat s.c. injection
(group IV,), yohimbine HCI1.7 mg/100 g body weight (group IV3) and caffeine
11.2 mg/100 g body weight (group IV4) showed significant elevation of (AST) while strychnine
HCI 24 g/100 g body weight (group IV2) caused no changes. Codeine phosphate, strychnine HCI,
yohimbine HCI and caffeine phosphate caused significant elevation of AST. There was no change
of ALP level after codeine injection while there were significant decrease of its levels
after strychnine, yohimbine and caffeine injection Total proteins and serum
198
SUMMARY
albumin showed significant decrease after codeine, strychnine. yohimbine and caffeine injeCtion,
that were confirmed by histopathological changes 1n the liver which showed mild congest1on
and mild portal tract inflammation with codeine injection. Congestion, intralobular
inflammation and focal steatosis with strychnine injection. Yohimbine injection showed marked
portal tract inflammation. While caffeine injection showed conges!lon only. Code1ne
injection causes no changes in BUN. While there was significant 1ncrease of its level after
strychnine HCI, yohimbine HCI and caffeine. Serum creatinine showed s1gn1ficant decrease in
its level after codeine, strychnine and yohimbine 1n]ect1on. While caffe1ne induced a
significant increase of its value.
These changes of BUN and creatinine were paralleled to
histopathological changes appeared in kidney tissue in the form of congestion and cloudy
swelling after injection of codeine, strychnine, yohimbine and caffeine.
Heart showed congestion with codeine, strychnine and caffeine
injection. While yohimbine caused congestion and focal degeneration of cardiac muscle
fibers.
Brain showed congestion with codeine, strychnine and caffeine injection but with
yohimbine there were congestion and focal edema.
All rats died after injection s.c. with 1/5 LD50 of a mixture of codeine
phosphate, strychnine HCI, yohimbine HCI and caffeine. So another trail is made by
injecting the rats with 1/10 LD50 of these mixtures, which revealed significant elevation of
liver enzymes (ALT and AST) and in mean time none significant decrease of total protein
and serum albumin and significant increase of BUN and serum creatinine.
There were significant histopathological changes detected in the liver as fatty changes and
portal tract infiltration with mononuclear inflammatory cells, Whereas kidney showed focally
dilated collecting tubules lined by degenerated cell with focal necrosis, also hyaline casts
were seen. Codeine mixture cause congestion and focal degeneration of cardiac muscles fibers.
Brain showed congestion, focal inflammation and edema.
5- Pethidine HCI 74 mg/100 g body weight rats s.c. injection caused significant elevation of
ALT and AST and non significant changes of ALP There were significant decrease of
total proteins, albumin, BUN and creatinine. Hislopathological changes detected in the
liver congestion and portal tract inflammation. Kidney showed congestion and cloudy swelling and
the heart and brain were congested.
199
SUMMARY
6- Sole Nova C 18 mg/100 g body weight rats (group Vl1 ) and sole Rohypnol 0.5 mg/1 00
g body weight rats (group Vl2 ) oral administration caused significant elevation of
serum liver enzyme (ALT, AST and ALP) There were significant decrease of total
proteins and serum albumin while there were sign1f1cant increase of BUN and no significant
change 1n serum creatinine level.
Histopathological changes after Nova C administration were detected
as congestion and portal tract inflammation of the liver. These changes increased
markedly w1th Rohypnol administration. Kidney showed congestion and interstitial inflammation in
both Nova C and Rohypnol administration while in Rohypnol there were cloudy swelling of
proximal convoluted tubules and focal atrophy of distal convoluted tubules. Heart showed
congestion and focal degeneration of cardiac muscle fibers after Nova C administration, While
with Rohypnol administration there were scattered inflammation and also focal degeneration
of cardiac muscle fibers. Brain showed congestion only after Nova C injection.
Nova C and Rohypnol combination given to rats (group V3) resulted in non-significant changes
on serum ALT level, while it caused significant increase of AST level. ALP level
was significantly decreased. There was significant decrease of serum total protein with no
change in serum albumin level. Also the two drugs in combination orally given caused
significant increase of BUN while no significant difference of serum creatinine was found.
Histopathological changes detected after Nova C and Rohypnol combination administration, showed
congestion of portal tract and interlobular inflammation and steatosis of the liver. Kidney
showed congestion, cloudy swelling and focal degeneration. Congestion, scattered
inflammation and focal degeneration of cardiac muscle fibers. While in brain there was
congestion and focal inflammation.
Xanthine! nicotinate injected i.p. 20 mg/100 g body weight rat in all opiate group
(morphine group 1112, codeine mixture IV6 and pethidine V2) caused improvement of
both biochemical and histopathological results of acute opiate intoxicated rats when compared
with control group and also with opiate group without X.N treatment.
Biochemical and histopathological changes do not return to normal values of control group
after two weeks of opiate injection. Whereas X. N. injection to Nova C and Rohypnol
combination group (group Vb) showed non significant improvement of neither biochemical nor
histopathological results.