Mediation of the schistosomicidal effect of praziquantel through nitric oxide.
The effect of praziquantel (CAS 55268-74-1) on serum nitrate/nitrite level (a marker for nitric oxide (NO) synthesis) in S. mansoni infected mice was studied. The effects of the NO precursor (L-arginine) and NO-synthase inhibitor (NG-nitro-L-arginine methyl ester, L-NAME) on the effect of praziquantel on nitrate/nitrite level as well as on its antischistosomal activity were also evaluated. Praziquantel increased nitrate/nitrite level in serum of infected mice in a dose dependent manner. An oral dose of 75 mg/kg praziquantel produces a significant (p < 0.05) increase in serum nitrate/nitrite level by about 3.5 fold. Administration of L-arginine (200 mg/kg orally) induced a significant (p < 0.05) increase in nitrate/nitrite level (to about 5 fold) compared to praziquantel 75 mg/kg alone. Praziquantel-induced increase in nitrate/nitrite level was significantly reduced by administration of L-NAME 100 mg/kg. The antischistosomal activity of praziquantel was evaluated using two models: hepatic shift model and reduction of worm burden. In the hepatic shift model, praziquantel increased the percentage of worms in the liver (from 5% in control to 60%). Praziquantel-induced hepatic shift was not significantly affected by concurrent L-arginine or L-NAME administration. In the second model, praziquantel induced a significant decrease of the worm burden (p < 0.05) and the action of praziquantel was significantly increased by L-arginine and reduced by L-NAME administration. In conclusion, NO is possibly involved in the antibilharzial effect of praziquantel and administration of L-arginine with praziquantel produces beneficial antibilharzial effect.
Ammar
Elsayed M
EM
Department of Pharmacology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Said
Shehta A
SA
Eissa
Laila A
LA
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008099:Liver / Q000469:parasitology; D051379:Mice; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011223:Praziquantel / Q000494:pharmacology*; D012550:Schistosoma mansoni / Q000187:drug effects*; D012556:Schistosomicides / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D012556:Schistosomicides; D009569:Nitric Oxide; D011223:Praziquantel; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester