الفهرس 
coverOnly 14 pages are availabe for public view
 |  | from | 153 |  |  |
| | | from | 153 | | |
Abstract
NSAIDs are one of the most frequently used classes of medicines in the
world and accounts for nearly 5% of all prescribed medications. It is expected
that the use of NSAIDs will increase because the incidence of rheumatic
diseases is also increasing. Regarding their side effects, symptoms like
dyspepsia, nausea, vomiting, abdominal pain and heartburn are the most usual
adverse gastro-intestinal (GI) effects linked to their use. NSAIDs can cause
serious complications as peptic ulcer or upper GI bleeding that require
hospitalization. Moreover, several NSAIDs have been withdrawn from the
market for various reasons. Among these are severe kidney impairment and
unacceptable hepatic hazards even if the risk is rare.
In the present study, possible hepatic impairments caused by NSAIDs
were investigated. Three different NSAIDs were used: a non-selective drug
(indomethacin), a partially selective one (nimesulide), and a selective COX-2
inhibitor (celecoxib). Albino rats weighing 180 to 220 g were used and divided
into two main groups as follows:
Group I: normal rats that were divided into 4 subgroups:
• Group I-A: -ve control group received distilled water orally twice daily
for 7 days.
• Group I-B: rats received nimesulide 18 mg/kg orally twice daily for 7
days.
• Group I-C: rats received celecoxib 18 mg/kg orally twice daily for 7 days.
• Group I-D: rats received indomethacin 9 mg/kg orally twice daily for 7
days.
Group II: TAA induced hepatotoxicity.
Induction of hepatotoxicity was performed by injecting the rats by
thioacetamide 50 mg/kg for three consecutive days. Then this group was
divided into 4 subgroups and received the drugs as previously explained:
• Group II-A: control group (TAA group).
• Group II-B: nimesulide treated group.
• Group II-C: celecoxib treated group.
• Group II-D: indomethacin treated group.
The effects of the three drugs on the liver and stomach tissues in rats were
compared. To assess the extent of liver affection, biochemical measurements,
specifically mean serum AST, ALT, ALP, bilirubin (total and direct), and
albumin, were measured. Several hepatic histo-pathological changes were also
recorded in each subgroup as the extent of necrosis, cholestasis, steatosis, portal
tract inflammation, lobular inflammation, fibrosis, sinusoidal and central vein
congestion. The gastric acidity and the mean ulcer score were also measured to
investigate the difference of the three drugs on the stomach.
It was found that nimesulide raised almost all the liver biochemical
parameters (AST, ALT, ALP, total and direct bilirubin) in comparison to the
control group and to the celecoxib and indomethacin treated groups in healthy
rats. Moreover, the nimesulide treated group showed hepatic mild necrosis,
cholestasis, steatosis, mild portal tract and lobular inflammation, some extent of
fibrosis, and congestion. The effects of celecoxib and indomethacin on hepatic
tissues were variable and generally less than the nimesulide effect.
The nimesulide did not affect the gastric acidity in comparison to
indomethacin which lowered the gastric pH value remarkably. Both nimesulide
and celecoxib did not affect the gastric tissues by gross and histo-pathological
examinations. In contrast, the indomethacin treated group showed hemorrhagic
Summary
It is concluded that:
• The pathological and biochemical changes in the gastric tissues are
minimal for both nimesulide and celecoxib. They are well tolerated and
do not produce harmful effects on stomach. On the other hand,
indomethacin caused harmful pathological and biochemical changes in
the gastric tissues.
• Regarding the effects on the liver, nimesulide had serious adverse effects
on the liver function tests and caused harmful pathological changes in the
hepatic tissues in adult rats. So, liver functions should be assessed when
nimesulide is administered in healthy individuals and the drug should be
avoided in cases of hepatic impairment as it can possibly worsen an
underlying hepatic disease.
Finally, since nimesulide showed good gastric tolerability and severe hepatic
insult, further investigations in adults are needed to compare the benefits versus
the risks of nimesulide. Such investigations are essential especially that the
dosage forms of that drug for children were withdrawn from the Egyptian
market since 2008.