title: Sulforaphane increases the survival rate in rats with fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide.
abstract: Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome, with liver transplantation being the only effective therapy. Sulforaphane (SFN) is a natural compound that is extracted from cruciferous vegetables and possesses potent anti-inflammatory, antioxidant, and anticancer activities. This study was designed to test the hypothesis that SFN (3 mg/kg) may protect against FHF induced in rats by administering a combination of D-galactosamine (GalN; 300 mg/kg) and lipopolysaccharide (LPS; 30 μg/kg). The rats were given a single intraperitoneal injection of SFN, 1 hour before the FHF induction. Sulforaphane reduced the mortality and alleviated the pathological liver injury. In addition, SFN significantly reduced the increase in serum aminotransferase activities and lipid peroxidation. The glutathione content decreased in the GalN/LPS group, and this decrease was attenuated by SFN. Increases in serum tumor necrosis factor α, interleukin-6, and interleukin-10, which were observed in GalN/LPS-treated rats, were significantly reduced after using SFN. The GalN/LPS treatment increased the expression of superoxide dismutase-1, glutathione peroxidase 2, catalase, and heme oxygenase-1 genes. Sulforaphane inhibited the induction of reactive oxygen species scavenging proteins. Moreover, SFN inhibited GalN/LPS-induced caspase-3 activation and suppressed FAS and FASL expression. These findings suggest that SFN alleviates GalN/LPS-induced liver injury, possibly by exerting antioxidant, anti-inflammatory, and antiapoptotic effects and modulating certain antioxidant defense enzymes.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: rabab.sayed@pharma.cu.edu.eg.
authors.forename: Rabab H
authors.initials: RH
authors.lastname: Sayed
authors.affiliation: Department of Cell Biology, National Research Centre, Cairo, Egypt.
authors.forename: Wagdy K B
authors.initials: WK
authors.lastname: Khalil
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Hesham A
authors.initials: HA
authors.lastname: Salem
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Sanaa A
authors.initials: SA
authors.lastname: Kenawy
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
authors.forename: Bahia M
authors.initials: BM
authors.lastname: El-Sayeh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000097:blood; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005688:Galactosamine / Q000009:adverse effects*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000097:blood; D051547:Heme Oxygenase-1 / Q000097:blood; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D017879:Isothiocyanates / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000009:adverse effects*; D017114:Liver Failure, Acute / Q000188:drug therapy*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013454:Sulfoxides; D013482:Superoxide Dismutase / Q000097:blood; D000072105:Superoxide Dismutase-1; D015996:Survival Rate; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D053222:Fas Ligand Protein; C491898:Fas protein, rat; C505662:Faslg protein, rat; D015850:Interleukin-6; D017879:Isothiocyanates; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D013454:Sulfoxides; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D016753:Interleukin-10; D005688:Galactosamine; D002374:Catalase; D005979:Glutathione Peroxidase; C525844:glutathione peroxidase 2, rat; D051547:Heme Oxygenase-1; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000637:Transaminases; C505410:Casp3 protein, rat; D053148:Caspase 3; C016766:sulforaphane; D005978:Glutathione
keywords: Apoptosis; Heme oxygenase-1; Lipopolysaccharide; Rat; Sulforaphane; d-Galactosamine