Iron depletion prevents adenine nucleotide decomposition and an increase of xanthine oxidase activity in the liver of the Long Evans Cinnamon (LEC) rat, an animal model of Wilson's disease.
The Long Evans Cinnamon (LEC) rat, which accumulates excess Cu in the liver as in patients with Wilson's disease, is a mutant strain displaying spontaneous hepatitis. It was reported that Fe, like Cu, increases in the liver and that the severity of hepatitis is modified by Fe in the diet. In this experiment, oxidative stress increased by Fe was investigated before the onset of hepatitis. To examine the effect of Fe on the progress into hepatitis, LEC female rats were fed an Fe-regular (Fe 214 microg/g; Fe(+) group) or an Fe-restricted (Fe 14 microg/g; Fe(-) group) diet from 53 days of age for 35 days. Fischer rats were also fed as control animals. Adenine nucleotide decomposition was determined as an index of oxidative stress based on xanthine oxidase activity. The size of the hepatic pool of adenine nucleotides (ATP+ADP+AMP) was significantly smaller in LEC rats than Fischer rats. The energy charge (ATP+0.5ADP)/(ATP+ADP+AMP) was smaller in Fe(+) groups than in Fe(-) groups. In the LEC rat liver, the Fe concentration in the Fe(+) group was 160% of that in Fe(-) group and the correlation coefficient between the hepatic Fe concentration and the energy charge was significant. In this strain, an increase of xanthine oxidase activity resulted in an increase of xanthine, an oxidized metabolite of hypoxanthine in the liver. The results suggest the involvement of the Fe in the progression into hepatitis in the LEC rat, even if the dietary Fe concentration is similar to that of commercial diet.
Sugawara
N
N
Department of Public Health, Sapporo Medical University, Japan.
Ohta
T
T
Lai
Y R
YR
Sugawara
C
C
Yuasa
M
M
Nakamura
M
M
Tamura
M
M
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D003300:Copper / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006527:Hepatolenticular Degeneration / Q000378:metabolism*; D007501:Iron / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D020318:Rats, Long-Evans; D017382:Reactive Oxygen Species; D014969:Xanthine Oxidase / Q000378:metabolism*
D000227:Adenine Nucleotides; D017382:Reactive Oxygen Species; D003300:Copper; D007501:Iron; D014969:Xanthine Oxidase