The impact of penicillamine and zinc in hepatic and brain tissues of copper-overloaded rats

Abstract

Objective: The aim of this study is to evaluate the efficacy of penicillamine and zinc sulphate in copper-loaded rats and to compare the copper reduction in hepatic and brain tissues. Material and methods: Thirty-five male albino Wistar rats were equally divided into 5 groups. The control group (G1) was given normal tap water, while the 4 groups (G2, 3, 4, 5) were supplied with copper-loaded water. After 5 weeks, rats in G1 and G2 were sacrificed. The remaining rats (G3, 4, 5) were given normal diet for the following 4 weeks. During that period, the fourth group (G4) was given zinc sulphate (6.5 mg/kg) and the fifth group (G5) received penicillamine (20 mg/kg). The third group (G3) was left untreated. Results: Amounts of copper deposited in hepatic tissues of G2 were significantly higher than G1 (p = 0.008). In G3, brain copper levels were significantly higher than G1 and G2 (p < 0.001 and 0.01, respectively), while hepatic concentrations were not statistically different. Rats in G5 had significantly lower hepatic and brain copper levels than G3 (p = 0.023 and < 0.001, respectively). There was a significant reduction in brain copper levels in G4, as compared to G3 (p = 0.003). Conclusion: The reduction of copper levels in both hepatic and brain tissues with penicillamine in copper-overloaded rats suggests that other mechanisms than the redistributive effect in the brain may be responsible for the neurologic deterioration induced by penicillamine treatment in patients with WD. Furthermore, zinc may have an early effect in prevention of excess copper deposition, probably by inducing metallothionin synthesis in the liver. In conclusion, zinc may be used in conjunction with chelating agents for the initial control of patients with neurologic symptoms.