Metallothionein and antioxidant enzymes in Long-Evans Cinnamon rats treated with zinc

Abstract

The Long-Evans Cinnamon (LEC) rat is a mutant animal model for Wilson's disease. It is known that an abnormal accumulation of Cu and Fe in the liver and low concentrations of both ceruloplasmin and Cu in the serum occur in these rats. The accumulation of Cu is explained by the defective expression of the Cu-transporting P-type ATPase gene, homologous to the gene for Wilson's disease (ATP7B). The aim of this work was to clarify the action mechanism of Zn, and to verify the role that this metal plays in LEC rats in short-term treatment experiments (1 and 2 weeks) on concentrations of Cu, Zn, Fe, metallothionein (MT), 8-hydroxy-2'-deoxyguanosine (oh(8)dG) and on the activity of antioxidant enzymes. It is well known that Zn induces MT and has the ability to prevent redox-active metals, Cu and Fe, binding to and causing oxidative damage at active sites of Zn metalloenzymes and nonspecific binding sites on proteins. Zn administration reduces Cu and Fe transport from mucosal to serosal intestinal sides through competitive mechanisms. Our findings show that treatment with zinc acetate increases tissue Zn and MT contents and decreases Cu and Fe concentrations in the liver and kidneys, even if hepatic Zn and MT concentrations decrease with treatment period. Induction of MT synthesis by Zn contributes to the reduction in free radicals produced by Cu and Fe. We also observed that the superoxide dismutase (SOD)activity in liver decreases with treatment duration in association with the Cu and Fe liver decrease. However, the SOD activity in kidney increases in untreated rats at 2 weeks relative to those untreated for 1 week.

Efficacy of zinc supplementation in preventing acute hepatitis in Long–Evans Cinnamon rats

“…These data have been previously published by our group (14,15). Briefly, MT liver, kidney and intestinal concentration in control rats was significantly higher after 8 weeks of the experiment compared with 1 and 2 weeks.…”

Evaluation of trace metals in tobacco of local and imported cigarette brands used in Pakistan by spectrophotometer through microwave digestion

“…Cu becomes toxic in case of excessive intracellular accumulation playing a role in initiating the generation of -totic processes (Medici et al, 2002;Santon et al, 2004). Zn becomes toxic in the case of excessive intake playing a role in induction of the pathological conditions that have been associated with oxidative stress (Yanagisawa et al, 2004).…”

Wilson's disease: Changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease

“…Previous studies on the pathogenesis of WD explored the possibilities of genetic polymorphisms in the ATP7B copper (Cu) transporter,5 alternative ATP7B gene splice variants,6 alterations in the RNA processing machinery,7 and the presence of gene modifiers 8. The mechanisms connecting Cu accumulation to hepatocyte damage are poorly understood and may include oxidative damage,9 apoptosis,10 and mitochondrial membrane cross‐linking 11…”