الفهرس 
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Abstract
Meloxicam and Tolfenamic acid are Non-steroidal anti-inflammatory drugs (NSAIDs) that, they primarily used for the treatment of acute or chronic conditions with pain and inflammation. Occurance of mainy side effects on the different organs of treated animals. This study was designed to determine some pharmacological properties of Meloxicam and Tolfenamic acid on male rates including its effect on fertility (testes index weight, epididimis index weight, sperm motility, sperm abnormalities and sperm count and their effects on level of testicular alkaline phosphatase, cholesterol , LDH and serum testosterone).
For this experiment Fourty four mature albino rats weighing from 140 – 180 gm body weight obtained from the faculty of Medicine, Alexandria University . They were housed in cages and fed on rice, barely, milk, bread and water ad-libitum. The animals were divided into 3 equal groups each of 15 rats. The first group was injected I/M for 3 times / week with a therapeutic dose of Meloxicam (1.80 mg / Kg B.Wt). The second group was injected I/M for 3 times/week with a Tolfenamic acid (9 mg/Kg B.Wt). The third group was kept as control and injected with 0.3 mL saline / rat for 3 times / week. At the end of 2nd , 4th , 8th week from drug administration, blood, body organs and epidemiological content were obtained from treated and control rats. All experimental rats were weighed at specific killing time.
The results are summarized as follows:
1-The effect of of meloxicam and tolfenamic acid on male reproductive organs weight:
a-Effect of meloxicam and tolfenamic acid on testis weight:-
It was found that i.m of meloxicam (1.80 mg/Kg B.Wt) or tolfenamic acid (9 mg /Kg B.Wt) on testes index weight at different periods from drug administration.indicated that , the tests index weight of higher values in control groups than the groups treated with meloxicam or tolfenamic acid and the difference among groups is statistically significant. And the meloxicam showed higher level in tests index weight than the tolfenamic acid but the difference between the meloxicam and tolfenamic acid not significantly different especially after 4-weeks and after 8-weeks of experiment while after 2-weeks it significantly different.
b-Effect of meloxicam and tolfenamic acid on epididymis weight:-
It was noticed that i.m of meloxicam (1.80 mg/Kg B.Wt) or tolfenamic acid (9 mg /Kg B.Wt) on epididymis index weight at different periods from drug administration. That there is a significant difference at different periods and among different treated groups and the higher level observed in control group followed by groups treated with tolfenamic acid and the lower level found in meloxicam treated groups.
2-The effect of meloxicam and tolfenamic acid on epididymal sperm characters:- The results in Table (3, 4 and 5) and Fig. (3, 4, 5) showed statistically significant differences among different groups and periods in their component of semen analysis (sperm motility, sperm abnormalities and sperm count).
a-Effect of meloxicam and tolfenamic acid on sperm motility:-
The results showed a higher level of sperm motility in control groups followed by meloxicam and finally the lower motility observed in tolfenamic acid. The level of sperm motility after 2 weeks in tolfenamic treated groups higher than that of the level in meloxicam treated group , while at 4 and 8 weeks the sperm motility in meloxicam treated group higher than that of tolfenamic treated group.
b-Effect of meloxicam and tolfenamic acid on sperm abnormalities: It was found that, the treatment with meloxicam and tolfenamic acid causing a higher sperm abnormalities than the control group. And the level of sperm abnormalities in tolfenamic treated group of higher level than the meloxicam treated group especially after 4 and 8 weeks of experiment.
c-Effect of meloxicam and tolfenamic acid on sperm cell count:
The results showed that the meloxicam treated group of a higher sperm count than the control group especially at 4 weeks of experiment followed by control group and the lower sperm count observed in the tolfenamic acid treated group.
3-The effect of meloxicam and tolfenamic acid on serum testosterone level :- The obtained results showed that there was a significant difference among different treated groups and among different periods of experiment on the level of serum testosterone. The level of serum testosterone in control group of higher level followed by tolfenamic acid treated group and the lowest level of testosterone observed in the meloxicam treated group.
4-Biochemical findings
Alkaline phosphatase (ALP):- The level of ALP in tolfenamic treated groups of higher level followed by the meloxicam treated group and the lower level observed in the control group. And the differences among groups were statistically significant. The level of ALP after 4 week of experiment higher than the level after 2-weeks and 8-weeks of experiment.
Lactate dehydrogenase (LDH):-The LDH level among different treated groups and different periods differ significantly. The higher level of LDH observed after 8-weeks of experiment. the groups treated with tolfenamic acid of a higher LDH level followed by meloxicam treated group and both of them higher than the control group.
Testicular cholersterol level:- The level of Testecular cholesterol differ significantly among different treatment groups and among different periods of experiment. The higher cholesterol level observed in the groups treated with tolfenamic acid followed by meloxicam treated group and the lower level observed in control group. And the level of cholesterol in the last period lower than that of the 1st period.
Histopathological findings
I. Rats treated with 1.80 mg Meloxicam/Kg B.Wt.
The microscopical examination of the parenchymatous organs of treated rats administered 1.80 mg meloxicam/Kg B.Wt., 3 times/week, revealed histopathological changes of the examined organs differ from control group.
Two weeks post Meloxicam administration
The testes showed congested blood vessels and mild interstitial oedema .The seminiferous tubules revealed mild cytoplasmic vacuolation of their lining epithelium. Moreover, exfoliation of the lining epithelial cells of some seminiferous tubules , accompanied by absence of the spermatozoa in their lumen were also seen. The prostate gland showed congested blood vessels and hyperplasia of the lining epithelial cells. The seminal vesicles showed congested blood vessels and extensive oedema admixed with inflammatory cellular infiltration of the interstitium mainly eosinophils and macrophages. The lymph vessels were also dilated and filled with eosinophilic proteinaceous material. Moreover, some seminal glands revealed desquamation of their lining epithelium admixed with inflammatory cells in the lumen .
Four weeks post Meloxicam administration
The testes showed congested blood vessels and mild interstitial oedema . The prostate gland showed congested blood vessels, interstitial oedema and cystic dilatation of some acini filled with eosinophilic secretion and lined by attenuated epithelium. The seminal vesicles showed congested blood vessels and marked interstitial oedema admixed with small focal areas of hemorrhages
Eight weeks post Meloxicam administration
The seminal vesicles showed moderate numbers of degenerated inflammatory cells in the lumen of some vesicle glands. The other parenchymatous organs revealed normal histological structures similar to control group.
II. Rats treated with 9 mg Tolfenamic acid/Kg B.Wt.
Two weeks post Tolfenamic acid administration: The testes showed congested blood vessels and interstitial oedema . The seminiferous tubules revealed normal histological appearance of many cases; however, vacuolation of germ cells in some seminiferous tubules accompanied by incomplete spermatogenesis and absence of spermatozoa in the lumen of the tubules were also observed. The prostate gland showed congested blood vessels, mild interstitial inflammatory cellular infiltration and hyperplasia of the lining epithelial cells. Occasionally, some prostatic acini were ectatic, lined by attenuated epithelium and contained eosinophilic secretion in their lumina. The seminal vesicles showed congested blood vessels and hyperplasia of the lining epithelial cells accompanied by focal hyDROPic degeneration. Multifocally, the interstitium of seminal vesicles were expanded by moderate infiltration of lymphocytes, macrophages and fewer plasma cells.
Four weeks post Tolfenamic acid administration: The testes showed congested blood vessels and mild interstitial oedema.. Rarely, the seminiferous tubules revealed mild cytoplasmic vacuolation of the lining epithelial cells. The seminal vesicles showed congested blood vessels and hyperplasia of the lining epithelial cells. Moreover, the interstitium of seminal vesicles were expanded by moderate infiltration of inflammatory cells mainly lymphocytes, macrophages and fewer plasma cells.
Eight weeks post Tolsinamic acid administration The testes showed congested blood vessels and mild interstitial edema. The seminal vesicles showed congested blood vessels and mild interstitial leucocytic cellular infiltration. Occasionally, some seminal glands revealed eosinophilic secretion admixed with desquamated epithelial cells. Furthermore, cellular and karyorrhectic debris were also detected in the lumen of some glands in few cases. The prostate gland showed congested blood vessels and mild interstitial inflammatory cellular infiltration.
III. Non treated control rats killed after 2, 4 and 8 weeks
No histopathological changes were detected in the examined organs of these rats.