Studies on the effects of the antimalarial drugs, chloroquine sulphate on phosphorus metabolism in rats
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Date
1970
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Abstract
Chloroquine sulphate (NIVAQUINB) is a member of 4-aminoquinolines used for treating acute malaria: due to infoctions "by Plasmodium vivax. Plasmodium falciparum. Plasmodium malariae and Plasmodium ovale.
The offect of chloroquine sulphate on phosphorus uptake and. its
metabolism in the red blood cells and the liver of rats has been studied
by radioisotopic and non-radioisotopic techniques in an attempt to find whether the drug has any influence on the phosphorus metabolism in these tissues.
Tho radioisotopic studies involved the treatment of albino rats with 100 ng/kg of chloroquine sulphate for 6, 12 and 24 hours. The blood samples were incubated with 32p_orthophosphate in Krobs Ringer solution, pH 7.4 and activities were determined by Geigor-Muller end window type counter. The activities were compared with control animals. There was no effect of the drug on the uptake of phosphorus by the red blood cells.
Studies were also made on the acute toxicity effects of the drug on phosphorus metabolism in the rod blood cells and the liver. The various phosphorus fractions if ore measured spec tro photometrically by the technique of Baginski et al (9). After administration of 100 mg/kg for 12 hours and 24 hours, there was no significant effect of the drug on phosphorus metabolism in the red blood cells.
Studies were also made/on the response of the different sexes to chloroquine sulphate. By comparing the results of the .males With those of the females, it has been submitted that administration of chloroquine sulphate might increase the synthesis of organic phosphates
in the rod blood cells of males and also in the plasma of females.
However, in chronic toxicity studies, daily administration of small doses of 5 mg/kg of chloroquine sulphate for 8 weeks resulted Ih increases of 35% and 27% in inorganic phosphate and total acid hydrolysable phosphates respectively in the red blood cells, whilst a decrease of about 16$ was noticed in the total phosphate of the plasma. An increase was also observed in the labile phosphate fraction. A long period of administration of the same dose for 16 weeks showed decreases in the bound and total phosphate fractions.
Acute toxicity studies in the liver by non-radioisotopic technique revealed increases in the total and bound phosphates. These increases were found to be due to an increase of 20% in the phospholipids. These findings suggest that there might be increased synthesis of phospholipids. Chronic toxicity studies showed no significant effects after daily doses of 5 mg/kg for 8 weeks, whilst increases of about 12% and 11% were noticed respectively in the inorganic and total acid soluble phosphates after 16 weeks of administration of fee same dose, It has been suggested that longer periods of administration of chloroquine sulphate might increase in the liver, the formation of enzyme systems that metabolise the drug administered into a more active form.
Finally studies on the effect of chloroquine sulphate on the activity of acid phosphatase in the red blood cells and the plasma by the method of king et al showed that the enzyme was not affected during acute toxicity studies.
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A Thesis
Presented for the Degree of Master of Science University of Science and Technology.
Department of Biochemistry University of Science and Technology Kumasi - Ghana.