title: Potential antifibrotic effects of AT1 receptor antagonist, losartan, and/or praziquantel on acute and chronic experimental liver fibrosis induced by Schistosoma mansoni.
abstract: 1. This study investigates the potential antifibrotic effect of losartan, AT-1 receptor antagonist, and/or praziquantel (PZQ) on acute and chronic hepatic fibrosis induced by Schistosoma mansoni (S. mansoni). 2. Schistosoma mansoni-infected mice were in two batches (I & II), each in four groups: (i) Infected untreated; (ii) treated with losartan, starting from the 4th or 12th weeks post-infection (PI); (iii) treated with PZQ in the 7th week PI; and (iv) treated with losartan, as group (ii) plus PZQ as group (iii). Comparable groups of uninfected mice were run in parallel with infected groups. Mice of batches I and II were killed 10 and 18 weeks PI, respectively. Hepatic content of hydroxyproline (HYP), serum levels and tissue expression of matrix metalloproteinase-2 (MMP-2), and transforming growth factor-β1 (TGF-β1) were determined. Parasitological, biochemical and histological parameters, which reflect disease severity and morbidity, were examined. 3. Losartan alone caused a considerable decrease in worm burden, hepatic tissue egg load with an increase in percentage of dead eggs, modulation of granuloma size and regression of inflammatory reactions, which was less obvious in the chronic stage. The best results were obtained when losartan was co-administered with PZQ, especially in the acute stage. This was revealed by a remarkable reduction in serum levels and tissue expression of MMP-2, TGF-β1 and HYP content, accompanied by conservation of hepatic reduced glutathione (GSH) versus the PZQ-treated group. 4. In conclusion, losartan has a promising antifibrotic action and could be introduced as a therapeutic tool with PZQ especially in acute schistosomal hepatic fibrosis.
authors.affiliation: Department of Pharmacology, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba, Giza, Egypt. naglaaellakkany@yahoo.com
authors.forename: Naglaa M
authors.initials: NM
authors.lastname: El-Lakkany
authors.forename: Walaa
authors.initials: W
authors.lastname: El-Maadawy
authors.forename: Afaf
authors.initials: A
authors.lastname: Ain-Shoka
authors.forename: Afkar
authors.initials: A
authors.lastname: Badawy
authors.forename: Olfat
authors.initials: O
authors.lastname: Hammam
authors.forename: Fatma
authors.initials: F
authors.lastname: Ebeid
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D005978:Glutathione / Q000378:metabolism; D006099:Granuloma / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008111:Liver Function Tests / Q000379:methods / Q000706:statistics & numerical data; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D010270:Parasite Egg Count; D011223:Praziquantel / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000378:metabolism
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000871:Anthelmintics; D053773:Transforming Growth Factor beta1; D011223:Praziquantel; D020778:Matrix Metalloproteinase 2; D005978:Glutathione; D019808:Losartan; D006909:Hydroxyproline