The embryotoxic and teratogenic effects of khat (Catha edulis Forsk.), a plant chewed by the people of Eastern Africa and Southern Arabia to attain a state of euphoria and stimulation, was studied in Wistar rats. Methanolic extract of khat was administered orally by gavage to rats during days from 6 to 15 of gestation at doses of 0, 125, 250 and 500 mg/kg. body weight/day. Khat reduced the food consumption and maternal weight gain and also lowered the food efficiency index, as compared to control mothers. On day 20 of gestation, all dams were sacrificed by cervical dislocation, cesarean sections were performed and maternal and fetal toxicities were assessed. The administration of khat had no effect on fetal sex ratio. However, at a dose of 125 mg/kg body weight and above, it produced a significant increase in resorptions and fetal wastage. Khat administration in utero also reduced the litter size and caused intrauterine growth retardation. External, visceral and skeletal examination of the fetus of treated dams showed several types of malformations and variations in all the groups of animals. However, a consistent tendency of abnormalities was observed in the highest dosed (500 mg/kg) group. The data of the present study revealed that khat retarded fetal growth and induced terata. The present observations indicate that khat possesses both embryotoxic as well as teratogenic properties. The developmental toxicities of khat are dose-related.
Biochemical and histopathological evaluations of the protective effects of the iron-chelator desferrioxamine against the cardiac and haematological toxicities of doxorubicin in normal rats were carried out. A single dose of doxorubicin (15 mg/kg, i.v.) caused myocardial damage that manifested biochemically as an elevation of serum cardiac enzyme [glutamic oxaloacetic transaminase (GOT), lactic dehydrogenase (LDH) and creatine phosphokinase (CPK)] and cardiac isoenzyme levels and histopathologically as a swelling and separation of cardiac muscle fibers. Doxorubicin caused severe leucopenia and decreases in red blood cell counts and haemoglobin concentrations at 72 h after its administration. Desferrioxamine treatment (250 mg/kg, i.p.) carried out 30 min before doxorubicin administration protected the heart and blood elements from the toxic effects of doxorubicin as indicated by the recovery of levels of cardiac enzymes and isoenzymes and of red blood cell counts to normal values and by the absence of significant myocardial lesions. The findings of this study suggest that desferrioxamine can potentially be used clinically to prevent doxorubicin-induced cardiac and haematological toxicities.
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