الفهرس 
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Abstract
Methotrexate is widely used in the therapy of various
types of diseases. It is used as a chemotherapeutic agent for
many cancer types and is also used for the treatment of
psoriasis, and rheumatoid arthritis. It causes numerous side
effects; the most serious side effect is hepatotoxicity.
Previous studies revealed that folic acid protected the liver
in Mtx treated patients but it might decrease the therapeutic
efficacy of the drug. Taurine has antioxidant and
antifibrotic properties, few studies were made to investigate
its role to protect against the ultrastructural changes and
fibrosis induced by Mtx. Hence, the aim of our present
study was to investigate the histological changes induced
by Mtx and to clarify the possible protective role of taurine
and folic acid.
Fourty two male albino rats were used and divided
into four groups. group I (control group) was subdivided
into four subgroups six rat each, group Ia the rats in this
group did not receive anything, group Ib the rats in this
group received intra-peritoneal saline twice weekly for six
weeks, group Ic the rats in this group received folic acid in
a dose of 250 mcg/kg using rat gavage needle for six weeks
and group Id the rats in this group received taurine at a dose
of 1000mg/kg daily using rat gavage needle for six weeks.
group II six rats in this group received methotrexate at a
dose of 0.5mg/kg by intra-peritoneal injection twice weekly
for six weeks. group III six rats in this group received methotrexate at a dose of 0.5mg/kg by intra-peritoneal
injection twice weekly for six weeks and at the same time
received folic acid in a dose of 250 mcg/kg daily using rat
gavage needle. group IV six rats in this group received
methotrexate at a dose of 0.5mg/kg by intra-peritoneal
injection twice weekly for six weeks and at the same time
received taurine at a dose of 1000mg/kg daily using rat
gavage needle. The specimens were processed and then
examined using both light and electron microscopes.
Light microscopic examination of liver sections
obtained from control group showed the hepatocytes
arranged in cords radiating around a central vein. The
hepatocytes were polygonal in form with acidophilic
cytoplasm and rounded basophilic nuclei having prominent
nucleoli. There was minimal collagen deposition. Electron
microscopic examination showed the hepatocyte with large
oval or rounded nuclei with one or two nucleoli surrounded
by nuclear membrane with peripheral condensation of
chromatin. The cytoplasm was occupied by mitochondria,
and rough endoplasmic reticulum and some inclusions were
also seen in the form of glycogen granules which appeared
as coarse, electron dense bodies.
Light microscopic examination of liver sections
obtained from group II showed marked distortion of hepatic
cords in their arrangement around the central veins which
also showed congestion and dilatation. The hepatocytes
appeared with ill-defined cell boundaries. The blood
sinusoids were markedly dilated and congested. Some hepatocytes nuclei showed irregular configuration. On the
other hand, there was a marked increase of collagen
deposition. Electron microscopic examination showed that
the most of the hepatocyte revealed wide areas of
degeneration in the form of vacuolation and fat droplets
that occupied the major parts of the cytoplasm. The
mitochondria were swollen with loss of their cristae. The
rough endoplasmic reticulum showed dilatation and
fragmentation.
Examination of the liver sections obtained from group
III revealed improvement in the histological appearance
compared to group II. Light microscopic examination of
liver sections from this group showed the hepatocytes
arranged as radiating cords around a central vein which still
showed dilatation and congestion and inflammatory cellular
infiltration in the periportal areas was still present. There
was incease in collagen deposition. Electron microscopic
examination showed that most of the hepatocytes had the
ultrastuctural pattern as that of the control group. Some
hepatocytes showed interrupted arrangement of rER and
loss of mitochondrial cristae.
Examination of the liver sections from group IV
showed that taurine succeeded to protect against the
harmful effects of Mtx on the liver to a reasonable degree.
Light microscopic examination of liver sections from this
group showed preservation of control pattern of
hepatocytes, they were organized around a central vein with
sinusoidal spaces between the hepatic cords; also there was minimal deposition of collagen fibers. Electron
microscopic examination showed that most of the
hepatocytes appeared normal.
The results were discussed and it was concluded that
taurine as well as folic acid protected the liver against
damage but taurine was more effective in protecting against
Mtx induced hepatic fibrosis. The use of folic acid remains
controversial; there is controversy over the optimum dose
of folic acid and over its effect on the therapeutic efficacy
of Mtx. These results might enhance the use of taurine as a
protective agent in Mtx induced hepatotoxicity. Hence, we
recommend further studies on the hepatoprotective effect of
taurine in chemically induced hepatic injury.