Leishmania major and Leishmania tropica: II. Effect of an immunomodulator, S(2) complex on the enzymes of the parasites.
S(2) complex has been reported to have a direct antileishmanial effect. The possibility that the direct antileishmanial effect may be due to inhibition of key enzymes involved in glucose metabolism and/ or enzymes associated with virulence was investigated. Cell pellets were prepared from cultures of both axenic amastigotes and promastigotes of Leishmania major (MHOM/IQ/93/MRC6) and L. tropica (MHOM/IQ/93/MRC2). S(2) complex, at various concentrations, was added to the enzyme extracts prepared from the pellets. Results show that in the Embden-Meyerhof pathway, both hexokinase and glucose-phosphate isomerase but not fructophosphokinase were dose dependently inhibited. In the hexose-monophosphate shunt both glucose-6-phosphate dehydrogenase and ribose-5-phosphate isomerase were dose dependently inhibited. Malic dehydrogenase and malic enzyme from the citric-acid cycle were both dose dependently inhibited but succinate dehydrogenase from the same pathway was not inhibited. Both enzymes associated with virulence (protease and acid phosphatase), showed activation rather than inhibition at higher doses of S(2) complex. Thus, the direct antileishmanial effect of S(2) complex may result, partially or entirely, from the inhibition of enzymes that are necessary for the parasites' carbohydrate metabolism.
Al-Mulla Hummadi
Yassir M
YM
Department of Pharmacology, College of Medicine, University of Baghdad, P.O. Box 61208, Baghdad 12114, Iraq.
Al-Bashir
Nada M
NM
Najim
Rafid A
RA
D000135:Acid Phosphatase / Q000187:drug effects / Q000378:metabolism; D019747:Aldose-Ketose Isomerases / Q000037:antagonists & inhibitors; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002952:Citric Acid Cycle / Q000187:drug effects; D003300:Copper / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors; D005954:Glucosephosphate Dehydrogenase / Q000037:antagonists & inhibitors; D006019:Glycolysis / Q000187:drug effects; D006593:Hexokinase / Q000037:antagonists & inhibitors; D007155:Immunologic Factors / Q000494:pharmacology*; D018320:Leishmania major / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D007895:Leishmania tropica / Q000187:drug effects / Q000201:enzymology* / Q000472:pathogenicity; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors; D009536:Niacinamide / Q000494:pharmacology*; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D010447:Peptide Hydrolases / Q000187:drug effects / Q000378:metabolism; D014774:Virulence
D000981:Antiprotozoal Agents; D007155:Immunologic Factors; C508300:S(2) complex; D009536:Niacinamide; D003300:Copper; D008291:Malate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D006593:Hexokinase; D000135:Acid Phosphatase; D010447:Peptide Hydrolases; D019747:Aldose-Ketose Isomerases; C022548:ribosephosphate isomerase; D005956:Glucose-6-Phosphate Isomerase; D001205:Ascorbic Acid