Pharmacological manipulation of the chronic granulomatous reactions in the livers of mice infected with schistosomiasis.
The severe granulomatous reactions in the liver which occur following infestation by adult Schistosoma mansonii are largely initiated by invading eosinophils and monocytes. The present studies were designed to investigate the possibility that (a) anti-inflammatory drugs could be employed beneficially to attenuate the liver granulomatous reactions in schistosomiasis, and (b) that part of the therapeutic effects of anti-schistosomal (AS) drugs might be due to possible influences on arachidonate metabolism. Therefore the effects were determined of (a) AS as compared with NSAI drugs on eicosanoid metabolism in isolated human peripheral leucocyte populations, and (b) electron-microscopic changes in the livers of mice infected with Schistosoma mansoni in response to AS and/or NSAI drugs. Of the AS drugs only praziquantel (10-100 microM) inhibited 5-HETE production by the 5-lipoxygenase pathway. No effects were observed of this or the other AS drugs on prostaglandin production. In S. mansoni infected mice, praziquantel (250 mg/kg/d), given orally with indomethacin (5 mg/kg/d) for 5 days did not improve the inflammatory reactions around worms or eggs of schistosomes. Furthermore, both indomethacin (5 mg/kg/d) alone and benoxaprofen (20 mg/kg/d for 5 days) elicited liver changes suggestive of specific liver damage by these drugs. These results suggest that liver pathology may be enhanced by NSAI drugs perhaps as a consequence of the liver metabolism of these drugs being compromised. Their use to modify inflammatory reactions at the peak of liver schistosome infections may thus be contraindicated.
D000818:Animals; D006099:Granuloma / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D007213:Indomethacin / Q000627:therapeutic use; D008109:Liver Diseases, Parasitic / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D011223:Praziquantel / Q000627:therapeutic use; D012550:Schistosoma mansoni; D012552:Schistosomiasis / Q000188:drug therapy* / Q000473:pathology; D012556:Schistosomicides / Q000627:therapeutic use*
D012556:Schistosomicides; D011223:Praziquantel; D007213:Indomethacin