الفهرس 
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Abstract
The present study was conducted to elucidate the possible adverse effects of the antibacterial agents, ceftiofur sodium and azithromycin, administered at therapeutic (7.2 and 45 mg/kg b.wt.) and double-therapeutic (14.4 and 90 mg/kg b.wt.) doses, respectively, on the mature male albino rats (200-250 gram) in two separate experiments. Male reproductive organs’ weights, spermiogram, testicular oxidative stress biomarkers, testosterone levels, liver function as well as histopathological investigation were evaluated.
Measurements were made at different periods (day 1, 30 and 60) post-treatment, to follow up the drug induced effects on the reproductive and hepatic functions.
In the first experiment ceftiofur sodium was administered once daily by subcutaneous route to male albino rats designated into six groups according to the dose (therapeutic dose; 7.2 mg/kg b.wt., double-therapeutic dose; 14.4 mg/kg b.wt. and control; 0 mg/kg b.wt.) and period of treatment (seven “first three groups” or fourteen days “other three groups”).
In the second experiment azithromycin was administered orally once daily at 45 mg/kg b.wt. (therapeutic dose), 90 mg/kg b.wt. (double-therapeutic dose) and 0 mg/kg b.wt. (control) for three (first three groups) or six (other three groups) days to male albino rats.
Six rats were sacrificed from each group at the first, thirty and sixty day after the last dose of administrations to evaluate the various effects of drugs on the male rat reproductive organs, spermiogram, testicular oxidative stress, testosterone level and liver function as well as the histopathological changes of the reproductive organs and liver.
The data recorded showed that:
1- Reproductive tract effects:
1) Ceftiofur sodium and azithromycin were noticed to induce a significant decrease in the index weight of the reproductive organs.
2) While the seminal vesicle’s weight and index weight of rats treated with azithromycin for three- (at double therapeutic dose) or six-days (at both doses) significantly decreased at the thirty day post-treatment, the gland weights increased markedly in rats treated with the double therapeutic dose for three days at the first day post-treatment.
3) Prostate gland weight markedly altered after azithromycin administration for 6 days at therapeutic (decrease) or double therapeutic (increase) doses in the first day post-treatment.
2- Spermiogram changes:
Sperm motility, livability and cell concentration decreased while sperm abnormalities increased markedly in all ceftiofur and azithromycin treated groups along the experimental periods. Though, the onset time of the alterations with respect to dose and duration of treatment was varied.
3- Hormonal changes:
1) Ceftiofur administration was associated with a decrease in the circulating testosterone level in 7-days and 14-days treated groups.
2) Azithromycin dosing for three days had not affect testosterone level significantly in comparison to control along the experimental period. However, testosterone concentration differed noticeably on the first day after the end of azithromycin dosing for six days.
4- Intra-testicular oxidative stress effects:
1) In ceftiofur groups, testicular oxidative stress markers significantly decreased
2) The effect of azithromycin dosing mostly centered on the thirty day post-treatment in the three- and six-days protocols.
5- Liver weights implications
1) Ceftiofur sodium induced a significant decrease in liver weights and index weights along the experimental period in rats treated for seven or fourteen days at both doses.
2) Azithromycin treated rats for three and six days’ treatment showed a significant decrease in liver weights, without influencing on the index weight, along the experimental periods regardless of the dose or the period post-treatment except at the thirty days after three days treatment where the liver index weight markedly decreased.
6- Liver function changes:
1) Rats administered ceftiofur sodium for 7 days (at both doses) showed a significant decrease in all liver enzymes along the period of the experiment.
2) In 14-days ceftiofur treatment (at both doses):
a) On the 1st day post-treatment, all liver enzymes except alanine aminotransferase significantly decreased, that was significantly increased.
b) On one and two months post treatment, liver enzymes except acid phosphatase significantly decreased.
3) Azithromycin treatment (for three and six days) negatively impacted on all liver enzymes except alkaline phosphatase enzyme along the experimental.
7- Histopathological changes:
a) Reproductive organs
1) Testicular tissues of ceftiofur were characterized by homogenous eosinophilic material and congestion in the blood vessels in the interstitial stroma. The epididymis of 14-days double-therapeutic group on 60th days showed histopathological alternation characterized by focal inflammatory cell’ infiltration.
2) There was a dose-dependent histopathological alterations in the liver of rats after ceftiofur administration for 7 and 14 days.
3) Azithromycin dosing (at 45 mg and 90 mg /kg b.wt.) for three days did not influence the histopathological architecture of the reproductive organs on the first and thirtieth days post-treatment.
4) Testicular tissue markedly changed in three days-treated rats at the sixty day, and in six-days treated groups along the experimental period after treatment with azithromycin.
5) Epididymis normally appeared except for lacking of spermatozoa (in three-days’ protocol on sixtieth day) and (in six-days’ protocol at the thirtieth and sixtieth day) after azithromycin treatment.
6) Seminal vesicles examination in azithromycin-six-days treated groups showed hyperplasia in the lining acinar epithelium in the therapeutic group.