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

• Published in: Journal of hepatology Vol. 48; no. 3; pp. 486 - 493
• Main Authors: Tsubota, Akihito, Yoshikawa, Tetsuya, Nariai, Koichi, Mitsunaga, Makoto, Yumoto, Yoko, Fukushima, Keiko, Hoshina, Sadayori, Fujise, Kiyotaka
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.03.2008; Elsevier
• Subjects: 8-OHdG; Animals; Biological and medical sciences; Caspase 3 - metabolism; Cattle; CpG island; CpG Islands - physiology; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - metabolism; Disease Models, Animal; DNA Damage - physiology; DNA Glycosylases - genetics; DNA Glycosylases - metabolism; DNA Methylation - drug effects; DNA Repair - physiology; DNA, Mitochondrial - metabolism; Down-Regulation; Female; Gastroenterology and Hepatology; Hepatitis - metabolism; Hepatitis - pathology; Lactoferrin - pharmacology; Liver - drug effects; Liver - enzymology; Liver - pathology; Liver Failure, Acute - metabolism; Liver Failure, Acute - pathology; Malondialdehyde - metabolism; Medical sciences; Metabolic diseases; Metals (hemochromatosis...); Methylation; Mitochondria, Liver - drug effects; Mitochondria, Liver - enzymology; OGG1; Other metabolic disorders; Rats; Rats, Inbred LEC; Wilson’s disease; Long-Evans Cinnamon; Wilson’s disease; OGG1; 8-oxoguanine DNA-glycosylase; 8-hydroxy-2 f-deoxyguanosine; ROS; reactive oxygen species; LEC; Methylation; CpG island; 8-OHdG; Nervous system diseases; Bovine; Wilson disease; Rat; Liver; Rodentia; Metabolic diseases; Enzymopathy; Genetic disease; Vertebrata; Lactoferrin; Mammalia; Animal; Digestive diseases; Artiodactyla; Copper; Wilson's disease; Ungulata
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2007.11.013

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.