Mediation of the schistosomicidal effect of praziquantel through nitric oxide

• Published in: Arzneimittel-Forschung Vol. 52; no. 11; p. 844
• Main Authors: Ammar, Elsayed M, Said, Shehta A, Eissa, Laila A
• Format: Journal Article
• Language: English
• Published: Germany 01.01.2002
• Subjects: Animals; Arginine - pharmacology; Enzyme Inhibitors - pharmacology; Liver - parasitology; Mice; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide - blood; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Praziquantel - pharmacology; Schistosoma mansoni - drug effects; Schistosomicides - pharmacology
• ISSN: 0004-4172
• DOI: 10.1055/s-0031-1299978

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.