Increased metallothionein in the liver and kidney of patients with amyotrophic lateral sclerosis
P. A. Sillevis Smitt, H. van Beek, A. J. Baars, D. Troost, E. S. Louwerse, A. C. Krops-Hermus, F. A. de Wolff and J. M. de Jong
Department of Neurology, Academic Medical Centre, Amsterdam, The Netherlands.
To evaluate the putative role of metals and trace elements in the
pathogenesis of classic amyotrophic lateral sclerosis, we studied the
metallothionein levels in liver and kidney samples obtained at autopsy from
24 patients with amyotrophic lateral sclerosis and 18 controls. To assay
metallothioneins and copper, cadmium, and zinc bound to metallothioneins,
we used high-performance liquid chromatography directly coupled to flame
atomic absorption spectrometry. Total cadmium, zinc, and copper
concentrations were determined separately with the use of graphite furnace
atomic absorption spectrometry with Zeeman background correction. The
median liver metallothionein level was 60.3 mg/kg (range, 9 to 318 mg/kg)
in the patients with amyotrophic lateral sclerosis and 12.6 mg/kg (range, 0
to 104.5 mg/kg) in the controls. In the kidney, median metallothionein
levels were 126.9 mg/kg (range, 44 to 387 mg/kg) in the patients with
amyotrophic lateral sclerosis and 64 mg/kg (range, 13.1 to 187 mg/kg) in
the controls. Total zinc, cadmium, and copper concentrations, as measured
by atomic absorption spectrometry, were not significantly different in
patients vs controls. Our finding of elevated metallothionein levels in
organs from patients with amyotrophic lateral sclerosis may indicate an
increased exposure to metals.
