Bovine lactoferrin potently inhibits liver mitochondrial 8-OHdG levels and retrieves hepatic OGG1 activities in Long-Evans Cinnamon rats.
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.
Tsubota
Akihito
A
Institute of Clinical Medicine and Research (ICMR), Jikei University School of Medicine, Kashiwa, Chiba, Japan. atsubo@jikei.ac.jp
Yoshikawa
Tetsuya
T
Nariai
Koichi
K
Mitsunaga
Makoto
M
Yumoto
Yoko
Y
Fukushima
Keiko
K
Hoshina
Sadayori
S
Fujise
Kiyotaka
K
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
D004272:DNA, Mitochondrial; D008315:Malondialdehyde; D000080242:8-Hydroxy-2'-Deoxyguanosine; D045647:DNA Glycosylases; C483741:OGG1 protein, rat; D007781:Lactoferrin; D053148:Caspase 3; D003849:Deoxyguanosine