Theses
Permanent URI for this communityhttp://197.255.125.131:4000/handle/123456789/22146
A long essay or dissertation or thesis involving personal research, written by postgraduates of University of Ghana for a university degree.
Browse
2 results
Search Results
Item The Metabolism Of Chloroquine Phosphate By Rat Liver Cell Fractions(University of Ghana, 1979-06) Yeboah, P.O.; Asante, G.S.; Toothill,C.; University of Ghana, College of Health Sciences, School of Biomedical and Allied Health Sciences, Department of Medical Biochemistry1. The metabolisn of chloroquine phosphate by the various subcellular fractions of the rat liver honnogenate has been studied. (a) Both the mitochondrial and soluble fractions were found to contain enzyme systems that degraded chloroquine to varying degrees. (b) The maximum activity of chloroquine degradation was however found in the microsomal fraction, 2. In vitro studies on the metabolisij of (ring-3-^C) chloroquine led to the conclusion that the microsomal subcellular fraction was capable of breaking chloroquine down to a minimum of eight metabolites in which the 4-aminoquinoline nucleus remained intact. 3. A number of 4-aminoquinoline derivatives, including the 4'-hydroxy, the 4'-aldehyde, the primary amine (SN 13617) derivatives of chloroquine have been successfully synthesized and characterized, 4. Using the synthesized derivatives of chloroquine as chromatographic standards, four of the eight metabolites of chloroquine (see ' 2 * above) were identified as the primary amine derivative (SN 13617), the 4'-hydroxy and the 4'-aldehyde derivatives and 7 -chloro-4-aminoquinoline. 5. Based on in vitro studies on the metabolism of both chloroquine and the synthesized derivatives by the hepatic microsomal fraction of rat, it has been tentatively suggested that the metabcLlic degradation of chloroquine proceeds by the formation of the following metabolit.££.• in the order: i) The hydroxychloroquine, HCQ (ie. the analogue of chloroquine in which a hydroxyl group has been substituted in the 2-position of N-ethyl groups). ii) The secondary amine derivative (SN 13616); iii) The primary amine derivative (SN 13617); iv) The 4'-aldehyde derivative, which is largely converted into the 4'-hydroxy derivative. 6 . An alternative pathway for the secondary amine derivative ('SN 13616) has also been proposed. Through this pathway, chloroquine may be converted through SN 13616 and an unidentified intermediate V, to a final product 4-amino-7-chloroquinoline. It has also been demonstrated that in presence of SKF 525A, the metabolism of chloroquine is apparently activated through the latter alternative pathway. 7. Evidence is also presented to show that the proposed pathway for chloroquine metabolism might be common to both the rat and man.Item In Vitro Studies on the Effect of Chloroquine Phosphate on the Metabolism of the Rat Red Blood Cells(University of Ghana, 1972-11) Yeboah, P.O.; Asante, G.S.; Larway, P.F.; Lovelace, C.A.; University of Ghana, College of Basic and Applied Sciences, School of Biological Sciences, Department of Biochemistry, Cell and Molecular BiologyEvidence is presented to show that in vitro. (1) High levels of chloroquine phosphate can induce hemolysis in the rat red blood cells; and (2) chloroquine-induced hemolysis is characterised by a fall in GSH levels, unless glucose is present in very high concentrations* Chloroquine phosphate is a member of the 4-aminoquinoline series of drugs used for treating acute malaria due to infection fctj Plasmodium vivdx« Plasmodium falciparum. Plasmodium malariae and Plasmodium ovale. In vitro studies were made on red blood cells incubated with chloroquine phosphate to investigate a possible chloroquine-induced hemolysis in rat red blood cells. A wide range of chloroquine phosphate concentrations were tested. After 4 hours incubation of the mixture at 3?°C; 6,3 1 10~% caused only - 2. hemolysis in the rat red blood cells; whereas 2.5 x 10 !-i chloroquine caused 66,5a hemolysis. Complete hemolysis was however observed when 4.2 x 10 chloroquine phosphate was used in the incubation system. -1 -2 Either 3.78 x 10 M glucose or 2,0 x 10 M ATP protected the red _2 blood cells from hemolysis induced by 2.5 x 10 M chloroquine phosphate. Hemolysis induced by chloroquine phosphate was found to be characterised by (a) a fall in GSH level, and (b) an increase in the osmotic fragility of the rat red blood cells. These characteristics are similar to primaquine- induced hemolysis in -.red blood cells. The possibility is discussed that based upon osmotic fragility studies, the site of hemolytic action of chloroquine phosphate could be directly on the red cell membrane where the drug might interfere with sulfhydryl groups.