Efficacy of zinc supplementation in preventing acute hepatitis in Long-Evans Cinnamon rats.
OBJECTIVE
Long-Evans Cinnamon (LEC) rats are characterized by an abnormal hepatic deposition of copper (Cu) due to a lack of the Cu-transporter P-type adenosine triphosphatase: accordingly, the strain is a good animal model of Wilson's disease. The effect of oral zinc (Zn) acetate treatment on the development of acute hepatitis and the biochemical parameters of Cu-induced liver damage was studied in 5-week-old LEC rats (n=52).


METHODS
Rats receiving 50 or 80 mg/ml/day Zn acetate by gavage and control rats receiving a daily dose of glucose solution 0.02 g/ml by gastric intubation were killed at 1, 2 or 8 weeks after the start of treatment.


RESULTS
Treatment with Zn acetate resulted in the prevention of acute hepatitis: 10 of the 13 untreated rats developed signs and symptoms compatible with acute hepatitis between the 6th and 7th week of treatment. Tissue metallothionein (MT) significantly increased in the treated rats and positively correlated with Zn concentrations within the liver. Control rats had a significantly higher iron concentration in the liver and kidneys compared with supplemented rats, after both short- and long-term experiments. 8-hydroxy-2'-deoxyguanosine amounts were significantly lower in untreated rats.


CONCLUSIONS
Zn acetate prevents acute hepatitis, by increasing tissue MT concentrations, reducing Cu absorption and interfering with Fe metabolism.
Medici
Valentina
V
Section of Gastroenterology, Department of Surgical and Gastroenterological Sciences, University of Padova, Italy.
Sturniolo
Giacomo Carlo
GC
Santon
Alessandro
A
D'Incà
Renata
R
Bortolami
Marina
M
Cardin
Romilda
R
Basso
Daniela
D
Albergoni
Vincenzo
V
Irato
Paola
P
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000284:Administration, Oral; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006520:Hepatitis, Animal / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007501:Iron / Q000737:chemistry / Q000378:metabolism; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D020011:Protective Agents / Q000627:therapeutic use*; D051381:Rats; D020332:Rats, Inbred LEC; D015032:Zinc / Q000032:analysis / Q000378:metabolism; D019345:Zinc Acetate / Q000627:therapeutic use*
D020011:Protective Agents; D000080242:8-Hydroxy-2'-Deoxyguanosine; D008668:Metallothionein; D007501:Iron; D019345:Zinc Acetate; D003849:Deoxyguanosine; D015032:Zinc