The effects of pyrimethamine sulfadoxine and berenil on glucose-6-phosphate dehydrogenase activity in Trypanosoma brucei brucei and Trypanosoma brucei congolese infected rats.

The effects of pyrimethamine sulfadoxine (PS) and Berenil on the glucose 6-phosphate dehydrogenase (G6PD) activity in the blood, brain, heart, kidney, liver and skeletal muscle tissues of Trypanosoma brucei bruccei (Tbb) and Trypanosoma brucei congolense (Tbc) infected Wistar rats were investigated. Forty-eight rats with a mean weight of 140.0 g were divided into 2 equal groups and separately treated with PS and Berenil. Each group was further subdivided into uninfected, infected with Tbb and infected with Tbc subgroups. The drugs were administered after parasitemia was confirmed via microscopic examination. G6PD activity, total organ protein and haemoglobin levels were determined spectrophtometrically in the hemolysate and homogenates of brain, heart, kidney, liver and skeletal muscle tissues. The results were statistically analysed by using the two-tailed student’s t-test. The results of the two types of trypanosomal infections showed that they were comparable and showing similar patterns. The hemolysate indicated the highest activity of G6PD followed by the homogenates of the brain, liver, heart, kidney and muscle in that order. PS- treated animals did not demonstrate a significantly different G6PD activity when compared with those treated with Berenil (p > 0.05) and the values between uninfected and infected animals (both Tbb and Tbc) did not differ significantly (p > 0.05). This suggests that the mechanism by which PS and Berenil effect anti-trypanosomal actions may not be via the regulation of the pentose phosphate pathway.

[1]  B. Cissé,et al.  Seasonal intermittent preventive treatment with artesunate and sulfadoxine-pyrimethamine for prevention of malaria in Senegalese children: a randomised, placebo-controlled, double-blind trial , 2006, The Lancet.

[2]  J. Kublin,et al.  Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial , 2004, The Lancet.

[3]  Michael P Barrett,et al.  The trypanosomiases , 2003, The Lancet.

[4]  F. Opperdoes,et al.  Enzymes of carbohydrate metabolism as potential drug targets. , 2001, International journal for parasitology.

[5]  F. Opperdoes,et al.  Molecular Characterization of the First Two Enzymes of the Pentose-phosphate Pathway of Trypanosoma brucei GLUCOSE-6-PHOSPHATE DEHYDROGENASE AND 6-PHOSPHOGLUCONOLACTONASE , 2000 .

[6]  F. Opperdoes,et al.  Purification, localisation and characterisation of glucose-6-phosphate dehydrogenase of Trypanosoma brucei. , 1999, Molecular and biochemical parasitology.

[7]  O. Doumbo,et al.  Community pyrimethamine-sulfadoxine use and prevalence of resistant Plasmodium falciparum genotypes in Mali: a model for deterring resistance. , 1996, The American journal of tropical medicine and hygiene.

[8]  S F Queener,et al.  Identification of highly potent and selective inhibitors of Toxoplasma gondii dihydrofolate reductase , 1993, Antimicrobial Agents and Chemotherapy.

[9]  Oliver H. Lowry,et al.  Protein measurement with the Folin phenol reagent. , 1951, The Journal of biological chemistry.

[10]  Yi Zheng,et al.  Rational Drug Design , 2012, Methods in Molecular Biology.

[11]  J. Keiser,et al.  New drugs for the treatment of human African trypanosomiasis: research and development. , 2001, Trends in parasitology.

[12]  C. Wang,et al.  Molecular mechanisms and therapeutic approaches to the treatment of African trypanosomiasis. , 1995, Annual review of pharmacology and toxicology.

[13]  K. Douglas.  Rational drug design in parasitology. , 1994, Parasitology today.

[14]  S. Yaffe.  New drugs for the treatment of asthma. , 1979, Delaware medical journal.

[15]  Ernest Beutler,et al.  Red Cell Metabolism: A Manual of Biochemical Methods , 1975 .