الفهرس 
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Abstract
The non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for the treatment of many cases of rheumatism and inflammatory disorders such as rheumatoid arthritis, osteoarthritis and anklyosing spondilitis. They are used also in treatment of many cases of intrauterine contraceptive device-induced dysmenorrhea and menorrhagia. Among the widely used anti-inflammatory drugs in the medical area is diclofenac sodium with the trade name ”Declophen” which inhibits cyclo-oxygenases, the rate-limiting enzymes that catalyse the formation of prostaglandins precursors from arachidonic acid. Prostaglandins play a role in the control of cell proliferation and regulation of immune functions. In spite of such beneficial effects of this drug, yet there are some medical reports have been frequently incriminated it for producing certain adverse consequences following its usage.
Hence, the present study was constructed for the evaluation and assessment of the expected pathogenic and toxic side effects of the non-steroidal anti-inflammatory drug (NSAID) diclofenac sodium on the pregnant mothers of albino mice and their fetuses on the morphological features including their body weights, body lengths as well as the expected skeletal malformations. The study was also devoted to show any pathological anomalies which might arise in the body organs, examplified by two essential ones, namely, the liver and the stomach of maternally treated fetuses.
The chosen doses of the NSAID in this survey are nearly comparable to the human cumulative therapeutic doses as well as double of that doses. Therefore, the doses used in such experiments were estimated to be equivalent 1.5 & 3mg/kg body weight.
In the present study, 60 pregnant female mice were being divided into six groups (10 mice each). The first two groups are considered as the control groups (C1& C2) and the last four groups (A, B, D & E) are the drug treated groups and the treatment was achieved in the following manner:-
Groups C1 & C2 in which each pregnant female was injected intraperitoneally (i.p.) with 0.1 ml distilled water (the solvent of the drug) daily for 6 days during pregnancy from day 1 till day 6 of gestation and for 8 days during pregnancy from day 7 till day 14 of gestation , respectively. Groups A & D in which each pregnant female was injected (i.p.) with 1.5 and 3mg/kg body weight of diclofenac sodium, respectively for 6 days during pregnancy from day 1 till day 6 of gestation. Groups B & E in which each female was injected (i.p.) with 1.5 and 3mg/kg body weight of diclofenac sodium, respectively for 8 days during pregnancy from day7 till day 14 of gestation.
The present investigation included morphological examination of both pregnant mothers and their maternally treated fetuses in addition to histological and ultrastructural examinations of the liver and the stomach of maternally treated fetuses. The skeletons of fetuses were also examined in control and experimental groups.
Morphological results:
The data recorded in the present investigation indicate that pregnant females of both control and experimental groups showed a steady increase in body weight during the whole gestation period. The mean body weight was less in the treated groups when compared with that of the control. Cases of abortions are recorded among mothers of the experimental groups. The percentages of abortions recorded 10, 30, 20 and 40% in pregnant mice of groups A, B, D and E, respectively. However, in maternally treated fetuses, the results displayed retardation of growth as indicated by the significant reduction of both body weight and body length. Maternally treated fetuses of groups B, D and E showed various degrees of gross malformations appeared in the form of stunting in size, open eyes, rudimentary limbs, malrotated limbs, short neck, polydactyly, absence of tail, grossly malformed body, presence of edema in different parts of the body and haemorrhage on the body surface. Skeletons of maternally treated fetuses exhibited growth retardation represented by shortness of some bones as well as lack of ossification of the bones of the skull and caudal vertebrae.
Histopathological and ultrastructural results:
At the light and electron microscopical levels, prominent tissue and cells impairments were observed in both the liver and the stomach of maternally treated fetuses compared with the control and can be summarized in the following:-
A-The liver: The main pathogenic effects of diclofenac sodium on the liver of maternally treated fetuses comprised the following main features:
from the histopathological point of view:
•Gradual degenerative features in the individual hepatocytes symptomized mainly by vacuolar and fatty degenerations with nuclear lesions reflected as pyknosis and karyolysis.
•Predominance of inflammatory cellular infiltration mainly of mononuclear leucocytes (lymphocytes) as a defensive mechanism.
•Widening of the hepatic sinusoids, with eroded and demolished epithelia besides, activation of the phagocytic Küpffer cells as another line of defensive mechanism.
•Rather haemorrhagic oedema was observed in the area of the deteriorated sinusoids.
from the ultrastructural point of view:
•The mitochondria displayed gradual devastations; they manifested obvious swelling or hypertrophy as well as condensation of their matrices. They lost their internal ridges and matrices.
•The cisternae of RER were dilated and fragmented into smaller stacks and frequently degranulated.
•The hepatic sinusoids showed marked disturbances and Küpffer cells were markedly activated as marked by the aggregation of lysosomes of variable electron density.
B- The stomach:
The main consequences of the gastric mucosa of the stomach of maternally treated fetuses with diclofenac sodium are summarized in the following:-
from the histopathological point of view:
•Marked sloughing, erosion, exfoliation and necrosis of the mucosal lining cells.
•The cytoplasm of their lining epithelial cells showed features of vacuolar degeneration as well as coagulative necrosis.The nuclei of the devastated cells manifested pyknosis and karyolysis.
•Inflammatory cellular infiltration concomitant with extravasations of blood from the damaged microvessels in the supporting lamina propria and in sub-mucosal connective tissue forming rather haemorrhagic oedema.
from the ultrastructural point of view:
•The surface epithelial (mucous) cells showed damage and disruption of their apical surfaces with marked sloughing and erosions that showed conspicuous destruction and loss of their apical microvilli.
•Diminution of their apical secretory mucous and zymogenic granules.
•The cytoplasmic organelles of all gastric mucosal cells (surface epithelial, parietal and zymogenic cells) were markedly changed, being in the form of dilation and fragmentation of RER into smaller stacks. The mitochondria displayed gradual devastations; they manifested obvious swelling or hypertrophy as well as condensation of their matrices. They lost their internal ridges and matrices and their limiting membrane are destructed.
•The intracellular canaliculi and tubulovesicles in the parietal cells had illustrated conspicuous damage and demolished microvilli and vesicular structure.
•Also, the nuclei showed some pathological changes appeared in the form of notching and irregular of their nuclear envelopes as well as condensation of their chromatin materials besides, rather features of chromatinolysis.