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تحميل الدليل التدريبي

أسئلة شائعة


 

English Summary

        The Present Research Project was conducted to examine the toxic, teratogenic and growth-suppressing effects of heptaplatin on embryos obtained from treated female mice. The females were treated intraperitoneally with the drug at the dose levels of 5.0, 10.0 or 12.5 mg/kg body weight on days D6-D8, D9-D11 or D12-D14 of gestation. The project also aimed to follow up offspring of some of the treated mothers during the period extending from parturition up to six weeks of age. The follow up included body weight, teratogenicity and mortality rate. Moreover, it was also planned to investigate the cytogenetical  effects of the dose levels 5.0, 10.0 or 12.5 mg/kg of the drug on the embryonic liver cells of the female  mice after 12, 24 and 48 hrs from exposure.

 

          In the Present Research Project, mature laboratory SWR/J mice aging 8-10 weeks and weighing 26.3–28.42 g were used. The mated animals were closely observed and the females were daily inspected for the presence of vaginal plugs and the date of plug detection was considered the zero date (D0) of gestation. Fetuses were examined on day 17 of pregnancy, and offspring were also examined at parturition and thereafter at weekly intervals up to 6 weeks of age.

 

The obtained results could be summarized as follow :

1.      Treated dams:

a.       Maternal toxicity was not observed in any of the treated dams at any dose level used at any treatment internal.

b.       The mean body weight gain of the treated dams on day 17 of their gestation was highly significantly (P<0.01) decreased when those dams treated during days 6-8 of pregnancy at 12.5 mg/kg of heptaplatin as compared with the control group. Moreover, treatment with the dose levels 10 and 12.5 mg/kg during the same period resulted in a significant (P<0.05) increase in the percentages of total embryonic resorption in some of the treated dams.

c.       The mean body weight gain of the treated dams on day 17 of their gestation was highly significantly (P<0.01) decreased when those dams treated during days 9-11 of pregnancy at 12.5 mg/kg of heptaplatin as compared with the control group. Furthermore, treatment with the same dose level of the drug during the same period resulted in a significant (P<0.05) increase in the percentage of total embryonic resorption in some of the treated dams.

d.       Treatment of the dams during days 12-14 of their gestation did not significantly affect the mean body weight gain of treated dams or the percentages of total embryonic resorption at any dose level used as compared with the control group.

 

2.      Embryos and fetuses :

a.       The mean number of live fetuses on day 17 of gestation was highly significantly (P<0.01) decreased and  the percentages of dead embryos and fetuses were  highly significantly (P<0.01) increased when dams were treated during days 6-8 of their pregnancy at 10 and 12.5 mg /kg of heptaplatin as compared with the control group. However, treatment during the same period at any dose level used did not significantly affect the mean live fetal body weight or induce any congenital malformations in those fetuses.

b.       The mean number of live fetuses on day 17 of gestation was highly significantly (P<0.01) decreased and the percentage of dead embryos and fetuses was highly significantly (P<0.01) increased when the dams were treated during days 9-11 of their pregnancy at 12.5 mg / kg of heptaplatin as compared with the control group. However, treatment during the some period at any dose level used did not significantly affect the mean live fetal body weight or induce any congenital malformations in those fetuses except a single malformed fetus at the dose level 12.5 mg / kg of the drug.

c.       The mean number of live fetuses on day 17 of gestation was significantly (P<0.05) decreased and the percentages of dead embryos and fetuses were highly significantly (P<0.01) increased when the dams were treated during days 12-14 of their pregnancy at 10 and 12.5 mg/kg of heptaplatin as compared with the control group. However, treatment during the same period at any dose level used did not significantly affect the mean live fetal body weight or induce any congenital malformations in those fetuses except a single malformed fetus at the dose level 12.5 mg/kg of the drug.

3.      Pups :

a.       The mean number of live pups at birth was highly significantly (P<0.01) decreased when the dams were treated during days   6-8 of their pregnancy at 12.5 mg/kg of heptaplatin as compared with the control group. Moreover, the total percentage of pups' mortality at the end of their sixth week of age was significantly (P<0.05) increased when the dams were treated during the same period at 5 mg/kg of the drug.

b.       The mean live pups' body weight from the second week till the end of sixth week of their age was highly significantly             (P<0.01) decreased when the dams were treated during days 6-8 of their pregnancy at 5 mg/kg  of heptaplatin as compared with the control group.

c.       The treatment of dams during days 9-11 of their gestation did not have any significant effect on the mean number of live pups at birth or during the six weeks of their ages at any dose level used as compared with the control group.

d.       The mean live pups' body weight from the second week till the end of the sixth week of their ages was highly significantly (P<0.01) decreased when the dams were treated during days 9-11 of their pregnancy at 5 m mg/kg of heptaplatin as compared with the control group.

e.       The treatment of dams during days 12-14 of their gestation did not have any significant effect on the mean number of live pups at birth or during the six weeks of their ages at any dose level used as compared with the control group.

f.       The mean live pups' body weight at birth was significantly       (P<0.05) decreased when the dams were treated during days 12-14 of their pregnancy at all dose levels used as compared with the control group.

 

4.      The cytogenetical effects :

The treatment of dams at all dose levels used of heptaplatin did not significantly affect the percentages of mitotic index or the percentages of chromosomal aberrations in the embryonic liver cells at any time interval used as compared with the control group.

 

5.      From the Present Research Project results and the results of some documented studies, we recommend the following :

a.       Histological and histochemical studies in mice or rats to investigate the possible pathological effects of heptaplatin on various organs of these animals.

b.       A study on some aspects of pharmacokinetics of heptaplatin, its bioavailability and  its effectiveness on embryos.

c.       Histological, histochemical and biochemical studies to investigate the reason(s) behind the death of some of the pups that obtained from heptaplatin treated pregnant females.

d.       A cytogenetical study on embryos, fetuses or newborn pups aimed to find the possible relationship between the cytogenetical effects of heptaplatin and its embryo- or fetolethal effects.

e.       A real and serious research aims to find an alternative way that does not include cytotoxic drugs in the treatment of cancer is highly recommended.

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