Bovine lactoferrin potently inhibits liver mitochondrial 8-OHdG levels and retrieves hepatic OGG1 activities in Long-Evans Cinnamon rats

J Hepatol. 2008 Mar;48(3):486-93. doi: 10.1016/j.jhep.2007.11.013. Epub 2007 Dec 27.

Abstract

Background/aims: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Animals
  • Caspase 3 / metabolism
  • Cattle
  • CpG Islands / physiology
  • DNA Damage / physiology
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism*
  • DNA Methylation / drug effects
  • DNA Repair / physiology
  • DNA, Mitochondrial / metabolism
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / metabolism
  • Disease Models, Animal
  • Down-Regulation
  • Female
  • Hepatitis / metabolism
  • Hepatitis / pathology
  • Lactoferrin / pharmacology*
  • Liver / drug effects
  • Liver / enzymology*
  • Liver / pathology
  • Liver Failure, Acute / metabolism
  • Liver Failure, Acute / pathology
  • Malondialdehyde / metabolism
  • Mitochondria, Liver / drug effects
  • Mitochondria, Liver / enzymology*
  • Rats
  • Rats, Inbred LEC

Substances

  • DNA, Mitochondrial
  • Malondialdehyde
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA Glycosylases
  • OGG1 protein, rat
  • Lactoferrin
  • Caspase 3
  • Deoxyguanosine