Effect of schistosomal infection and its treatment on some key enzymes of glucose metabolism in mice livers.
Three antischistosomal drugs, praziquantel (CAS 55268-74-1, EMBAY 8440, Prz), oxamniquine (CAS 21738-42-1, Oxa) and oltipraz (CAS 64224-21-1, Olt) were examined for their ability to reverse the disturbances in carbohydrate metabolism induced by Schistosoma mansoni (S. mansoni) infection. The infected mice were screened every 2 weeks for 16 weeks for their body and liver weights in addition to assessment of the activities of liver pyruvate kinase (PK), phosphofructokinase (PFK) (glycolysis), citrate synthase (CS) (Krebs' cycle) glycogen phosphorylase (GP) (glycogenolysis), glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH) (hexose monophosphate shunt). Results of the study showed that infection with S. mansoni caused the following changes in mice livers: 1. significant increase in liver weights from the 6th week of infection, which coincided with schistosomal egg deposition, whereas body weights were reduced, 2. remarkable increase in the activities of PK and PFK from the 4th week of infection, 3. marked reduction in CS, GP, G6PDH and 6PGDH. These results lead to the conclusion that glycolysis is largely stimulated in the livers of infected mice on the expense of other metabolic pathways of glucose utilization. Administration of Prz to infected mice caused normalization of all measured enzyme activities almost from the 2nd week of infection, whereas liver and body weights were improved from the 10th week. Oxa was less effective in these regards while Olt was the least. These data support the selection of Prz as a drug of choice for S. mansoni infection.
Ahmed
S A
SA
Department of Medicinal Chemistry, National Research Center, Cairo, Egypt.
Gad
M Z
MZ
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002952:Citric Acid Cycle / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008112:Liver Glycogen / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010073:Oxamniquine / Q000627:therapeutic use / Q000633:toxicity; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D011223:Praziquantel / Q000627:therapeutic use / Q000633:toxicity; D011719:Pyrazines / Q000627:therapeutic use / Q000633:toxicity; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000201:enzymology*; D012556:Schistosomicides / Q000627:therapeutic use* / Q000633:toxicity; D013871:Thiones; D013876:Thiophenes
D008112:Liver Glycogen; D011719:Pyrazines; D012556:Schistosomicides; D013871:Thiones; D013876:Thiophenes; D010073:Oxamniquine; D011223:Praziquantel; C026209:oltipraz; D005947:Glucose