title: Modulation of thioacetamide-induced liver fibrosis/cirrhosis by sildenafil treatment.
abstract: Sildenafil citrate is a phosphodiesterase-5 inhibitor, approved for the treatment of erectile dysfunction. It enhances nitric-oxide-induced vasodilatation and it promotes angiogenesis. A relationship between angiogenesis and hepatic fibrosis has long been speculated, where the 2 are believed to progress together. In this study, the ability of sildenafil (10 mg·(kg body mass)(-1), orally, once daily) to prevent and also reverse liver fibrosis/cirrhosis experimentally induced by thioacetamide injection (200 mg·kg(-1), intraperitoneal (i.p.), 3 times·week(-1)) in male Sprague-Dawley rats has been investigated. Sildenafil administration, either to prevent or to reverse liver fibrosis/cirrhosis significantly improved the estimated hepatic functions, reduced hepatic hydroxyproline and, in turn, hepatic collagen content, as well as reducing serum levels of the pro-fibrogenic mediator transforming growth factor β1. In co-ordination with such improvement, fibrosis grades declined and fibrosis retracted. Herein, the observed results provide evidence for the potential therapeutic efficacy of sildenafil as an antifibrotic agent.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
authors.forename: Eman
authors.initials: E
authors.lastname: Said
authors.forename: Shehta A
authors.initials: SA
authors.lastname: Said
authors.forename: Nariman M
authors.initials: NM
authors.lastname: Gameil
authors.forename: Elsayed M
authors.initials: EM
authors.lastname: Ammar
mesh_terms: D000818:Animals; D003094:Collagen / Q000378:metabolism; D018450:Disease Progression; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*; D013853:Thioacetamide / Q000009:adverse effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D053773:Transforming Growth Factor beta1; D013853:Thioacetamide; D003094:Collagen; D000068677:Sildenafil Citrate; D006909:Hydroxyproline