Efficacy and mechanism of action of arachidonic acid in the treatment of hamsters infected with Schistosoma mansoni or Schistosoma haematobium

• Published in: International journal of antimicrobial agents Vol. 39; no. 3; pp. 232 - 239
• Main Authors: Ridi, Rashika El, Tallima, Hatem, Salah, Mohamed, Aboueldahab, Marwa, Fahmy, Omar M, Al-Halbosiy, Mohammad Farhan, Mahmoud, Soheir S
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.03.2012; Elsevier
• Subjects: adults; Animals; anti-infective agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; antibodies; antigens; Antigens, Helminth - metabolism; Arachidonic acid; Arachidonic Acid - administration & dosage; Arachidonic Acid - pharmacology; Biological and medical sciences; blood serum; Cell Membrane - drug effects; Cell Membrane - metabolism; Cricetinae; Drug Evaluation, Preclinical; eggs; Female; fluorescent antibody technique; Fluorescent Antibody Technique, Indirect; hamsters; Immune effectors; Infectious Disease; laboratory animals; Leukocytes, Mononuclear - metabolism; Liver - parasitology; Liver - pathology; Male; mechanism of action; Medical sciences; Mesocricetus; Microscopy, Electron, Scanning; mononuclear leukocytes; oral administration; Parasite Egg Count; parasites; Pharmacology. Drug treatments; Schistosoma haematobium; Schistosoma haematobium - drug effects; Schistosoma haematobium - pathogenicity; Schistosoma mansoni; Schistosoma mansoni - drug effects; Schistosoma mansoni - pathogenicity; Schistosomiasis - drug therapy; Schistosomiasis - parasitology; Schistosomicides; Schistosomicides - administration & dosage; Schistosomicides - pharmacology; Time Factors; Schistosoma mansoni; Schistosoma haematobium; Immune effectors; Arachidonic acid; Schistosomicides; Treatment efficiency; Rodentia; Plathelmintha; Effector; Trematoda; Infection; Vertebrata; Mammalia; Treatment; Animal; Helmintha; Invertebrata; Mechanism of action; Hamster
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2011.08.019

We have recently shown that in vitro and in vivo exposure of Schistosoma mansoni and Schistosoma haematobium to 5–10mM arachidonic acid (ARA) induces parasite surface membrane disintegration and eventual attrition. Here we report on the optimum ARA dose and post-infection treatment time for maximum schistosome demise in hamsters. A series of four experiments for each schistosome species indicated that oral administration of ARA after patency led to a highly significant (P<0.02 to <0.001) reduction in worm burden accompanied by a significant (P<0.05) decrease in worm egg load. ARA-mediated attrition in vivo appeared to be associated with high titres of serum antibodies to tegumental antigens. In support, serum antibodies from patently infected and ARA-treated hamsters readily bound to the surface membrane of ARA-exposed adult worms, as judged by indirect membrane immunofluorescence. More importantly, addition of serum antibodies and peripheral blood mononuclear cells significantly enhanced ARA-mediated adult worm attrition in vitro. These data together show that the schistosomicidal effect of ARA in laboratory animals is enhanced by immune effectors and is highly efficacious and entirely safe.