title: Bovine lactoferrin potently inhibits liver mitochondrial 8-OHdG levels and retrieves hepatic OGG1 activities in Long-Evans Cinnamon rats.
abstract: OBJECTIVE
  To assess the effect of lactoferrin on oxidative liver damage and its mechanism, we used Long-Evans Cinnamon (LEC) rats that spontaneously develop fulminant-like hepatitis and lethal hepatic failure.
  
  
  METHODS
  Four-week-old female LEC rats were divided into the untreated and treated groups. The latter was fed bovine lactoferrin at 2% mixed with conventional diet.
  
  
  RESULTS
  The cumulative survival rates were 75.0% vs. 100% at 14 weeks, 37.5% vs. 91.7% at 15 weeks, and 12.5% vs. 91.7% at 16 weeks, respectively, for untreated and treated rats (P=0.0008). The 8-OHdG levels in liver mitochondrial DNA and malondialdehyde in plasma and liver tissues were significantly lower in treated than untreated rats (P<0.001, =0.017 and 0.034, respectively). Mitochondrial DNA mutations were more common in untreated rats. OGG1 mRNA and protein expression levels were significantly lower in untreated than treated rats (P=0.003 and 0.007, respectively). Hypermethylation of the second CpG island located upstream of OGG1 gene was observed in untreated rats.
  
  
  CONCLUSIONS
  Our findings indicated that lactoferrin inhibits oxidative liver damage in LEC rats. Lactoferrin could be potentially useful for the treatment of oxidative stress-induced liver diseases.
authors.affiliation: Institute of Clinical Medicine and Research (ICMR), Jikei University School of Medicine, Kashiwa, Chiba, Japan. atsubo@jikei.ac.jp
authors.forename: Akihito
authors.initials: A
authors.lastname: Tsubota
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Nariai
authors.forename: Makoto
authors.initials: M
authors.lastname: Mitsunaga
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yumoto
authors.forename: Keiko
authors.initials: K
authors.lastname: Fukushima
authors.forename: Sadayori
authors.initials: S
authors.lastname: Hoshina
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Fujise
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002417:Cattle; D018899:CpG Islands / Q000502:physiology; D004249:DNA Damage / Q000502:physiology; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D004260:DNA Repair / Q000502:physiology; D004272:DNA, Mitochondrial / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D006505:Hepatitis / Q000378:metabolism / Q000473:pathology; D007781:Lactoferrin / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D017114:Liver Failure, Acute / Q000378:metabolism / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D020332:Rats, Inbred LEC
chemical_list: D004272:DNA, Mitochondrial; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; D007781:Lactoferrin; D053148:Caspase 3; D003849:Deoxyguanosine