title: Pre- or post-treatment with hepatocyte growth factor prevents glycerol-induced acute renal failure.
abstract: Hepatocyte growth factor (HGF) is known to have beneficial effects against damage in various organs, including liver, kidney and lung, in disease models. Previously, we reported that repeated administration of HGF ameliorates renal dysfunction and histological alteration of glycerol-injected rats, an animal model for severe acute renal failure (ARF). In the present study, we investigated in more detail the efficacy of pre- and post-treatment of HGF in this model. ARF was induced by intramuscular injection of glycerol into the hind limbs of male Wistar rats. The efficacy of pre-treatment was studied by intravenous injection of HGF (1 mg/kg) or vehicle 1 and 18 hours prior to glycerol injection. Pre-treatment of HGF dramatically protected glycerol-induced ARF rats against death, and prevented deterioration of biochemical parameters for renal function. We also analyzed expression of heme oxygenase-1 (HO-1), a cytoprotective protein, in kidney of HGF-injected rats. Intravenous administration of HGF enhanced renal expression of HO-1 mRNA from 1 to 3 hours after injection. Next, as a post-treatment study, HGF (1 mg/kg/3 hours) with dopamine was infused into glycerol-induced ARF rats 7 hours after glycerol injection. Intravenous infusion of HGF after ARF onset also ameliorated renal biochemical parameters. These results indicate that pre-treatment of HGF can improve ARF, and induction of HO-1 expression in kidney may be a cause of the protective effect. In addition, post-treatment of HGF with dopamine was also effective against the establishment of ARF.
authors.affiliation: Discovery Research Laboratories I, Sumitomo Pharmaceuticals Research Division, Konohana-ku, Osaka, Japan.
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Nagano
authors.forename: Ikue
authors.initials: I
authors.lastname: Mori-Kudo
authors.forename: Takao
authors.initials: T
authors.lastname: Kawamura
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Taiji
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Noguchi
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology*; D000818:Animals; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D005990:Glycerol; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D017228:Hepatocyte Growth Factor / Q000502:physiology / Q000627:therapeutic use*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D008934:Mitogens / Q000502:physiology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: C066855:HGF protein, human; D008934:Mitogens; D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D005990:Glycerol