Browsing by Author "Lartey, S.N-A."
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Item In Vivo Assessment of the Embryotoxicity of Chloroquine in the Rat(University of Ghana, 2004-06) Lartey, S.N-A.; Tagoe, C.N.B.; Lawson, A.L.; Addae, F.K.; University of Ghana, College of Health Sciences, School of Biomedical and Allied Health Sciences, Department of AnatomyThe embryotoxicity potentials of normal dosage regimens of chloroquine used for therapeutic purposes were assessed in this research. Accordingly, five dosage regimens (7. 5, 10.0, 12.5 15.0 and 20.0mg/kg body weight) of chloroquine diphosphate were screened by the High Performance Liquid Chromatography (HPLC) method to select those, which will provide whole blood levels in the (Sprague Dawley) rats comparable to those achievable during therapeutic use. The dosages of 7.5, 10.0 and 12.5 mg/kg body weight produced peak levels of 1, 811.80 ng/ml (3.5 μM) l688.34 ng/ml (3.3 -μM) and 1,125.54 ng/ml (2.5 μM) respectively and were selected for the embryotoxicity studies. These were injected intraperitoneally into pregnant -Sprague-Dawley rats on day 9½ of conception to assess their possible embryotoxicity over a 48-hour period. The results suggest a possible embryotoxicity of the dosages applied, even at those relatively low concentrations: They also indicated that there was a relationship between the dosage of chloroquine injected intraperitoneally and the peak blood concentration but not the time the peak concentrations of the drug was achieved. The drug produced varying degrees of growth retardation and dysmorphogenesis in the embryos and these were generally found to be dose related. Dysmorphogenesis was assessed as 10% in the control, 16% in the 7.5 mgCQ/kg body weight, 14% in the 10.0 mgCQ/kg body weight and 17% -in the 12.5 mgCQ/kg body weight treatment. The most common morphological abnormalities were abnormal axial rotation; unfused and underdeveloped cranial neural tube, microophthalmia and abnormal otic an optic primordia. At treatments of 10.0 mgCQ/kg and 12.5 mgCQ/kg body weight there were significant reductions in yolk sac diameter to 80% and 71%, respectively. Total protein contents were also reduced to 53% and 45%, head lengths to 67% and 65%, and crown-rump lengths to 80% and 70%, of control values. There were no significant reductions however, in the number of somites and the total morphological scores. Finally, the results from the study showed that the racemic chloroquine applied was- emhryotoxic even at those relatively low dosages.