Alessandro Santon

Effect and possible role of Zn treatment in LEC rats, an animal model of Wilson's disease

The effect of oral zinc (Zn) treatment was studied in the liver, kidneys and intestine of Long-Evans Cinnamon (LEC) rats in relation to metals interaction and concentration of metallothionein (MT) and glutathione (GSH). We also investigated the change in the activity of antioxidant enzymes and determined the biochemical profile in the blood and metal levels in urine. We showed that the Zn-treated group had higher levels of MT in the hepatic and intestinal cells compared to both untreated and basal groups. Tissue Zn concentrations were significantly higher in the Zn-treated group compared to those untreated and basal, whereas Cu and Fe concentrations decreased. The antioxidant enzyme activities in the Zn-treated group did not change significantly with respect to those in the basal group, except for hepatic glutathione peroxidase activity. Moreover, the biochemical data in the blood of Zn-treated group clearly ascertain no liver damage. These observations suggest an important role for Zn in relation not only to its ability to compete with other metals at the level of absorption in the gastrointestinal tract producing a decrease in the hepatic and renal Cu and Fe deposits, but also to MT induction as free radical scavenger.

Efficacy of zinc treatment against iron-induced toxicity in rat hepatoma cell line H4-II-E-C3

Objective: In this study, we have attempted to explore the possible protection afforded by Zn with regard to its antioxidant potential properties in the iron‐induced toxicity.

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

Objectives: Objectives: 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 Wilsons 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).

The influence of metallothionein on exposure to metals: An in vitro study on cellular models

In the present study, the interactions between zinc (Zn) and copper (Cu) or iron (Fe) have been examined. Rat hepatoma cell line H4-II-E-C3, fibroblast cell line mutant MT-/-, and wild-type MT+/+ cells treated with ZnSO4 or CuSO4 or FeSO4 or CuSO4+ZnSO4 or ZnSO4+FeSO4 for different times have been employed to study the effect of metallothionein (MT), glutathione (GSH) and metal (Cu, Fe and Zn) accumulation during cellular adaptation to supraphysiological metal concentrations. To investigate the different biological functions in the processes of metal homeostasis and detoxification, the levels of both MT-1 and MT-2 mRNAs have been evaluated. The three cell lines responded differently to metal treatments suggesting that the uptake and storage of these metals are affected by the specific cellular model and MT presence. In particular, Zn treatment significantly decreased Fe accumulation (p<0.05), whereas MT induced by Zn increased intracellular Cu content (p<0.05). Moreover, in H4-II-E-C3 cells administration of metals resulted in a rapid and transient induction of MT (p<0.05) and in GSH accumulation (p<0.05) suggesting synergistic interactions in which both appear essential for a protective regulatory function against the redox activity of metals. Taken together these results demonstrate that Zn affects the cellular levels of Cu and Fe by competition with the same ligand sites and/or by coordinate regulation of MT and GSH content.

Interactions between metals in rat liver and kidney: localization of metallothionein.

The interactions between two essential metals, Cu and Zn, and the localization and concentration of metallothionein have been studied in rat liver and kidney. Rats receiving daily intraperitoneal injections of Cu for 3 days, or Zn for 2 days, or Cu for 3 days followed by Zn for 2 days, were sacrificed 24, 72, 120 h after the final injection. Our data indicate that Cu and Zn are both good inductors of metallothionein synthesis in rat tissues. Synergism between Cu and Zn in metallothionein synthesis was also observed as indicated by immunocytochemical experiments and chemical analysis. Moreover, in rats injected with Cu followed by Zn, the localization of metallothionein and the concentrations of both metallothionein and metal differed over time according to the organs considered. In rat kidney, a delay in the excretory process was also observed and metallothionein was present 120 h after the last injection.