On the mechanism of lanthanide-induced liver toxicity

Abstract

The intravenous injection of the lighter lanthanide ions Pr(III), Nd(III), and Sm(III) in doses of 35 mumoles/kg inhibits, and isoosmolar doses of the heavier lanthanide ions Gd(III), Dy(III), and Er(III) stimulate rat liver nuclear in vitro RNA synthesis catalyzed by RNA polymerase B 24 h after their application, while nuclear RNA synthesis, catalyzed by RNA polymerase A, was inhibited by the same isoosmolar doses of Pr(III), Nd(III) and not influenced by Sm(III), Gd(III), Dy(III), or Er(III). The effect of in vivo applied Pr(III) and Nd(III) on rat liver in vitro nuclear RNA synthesis shows a similar time and dose-dependent pattern. The decreased rat liver nuclear in vitro RNA synthesis 24 h after intravenous injection of Pr(III) as well as after Nd(III) was accompanied by a decreased nuclear in vitro 3H-acetate uptake by the chromatin-bound histone fractions, F 2a2, F 3, and F 2al. At the same time after the Pr(III) injection, the capacity and number of initiation sites of the rat liver nuclear template for homologous nuclear RNA polymerases, prepared from control rat liver nuclei, was lower than the corresponding control template. A decreased activity of endogenous free nuclear RNA polymerases, as determined with the aim of the synthetic poly(dA-dT) template 24 h after Pr(III), may further contribute to the decreased nuclear RNA synthesis. The results indicate a primary ionic size-correlated interference of lanthanides with the nuclear control mechanisms of RNA synthesis.

Exposure, Metabolism, and Toxicity of Rare Earths and Related Compounds

“…There are differences in changes of RNA polymerase II activity among nitrates of Pr, Nd, Sm, Gd, Dy, and Er (120). The first three RE decreased RNA polymerase II activity while the latter three RE increased the activity; only Pr and Nd nitrates decreased RNA polymerase I activity while the other four did not change the RNA polymerase I activity.…”

Differences in Behavior among the Chlorides of Seven Rare Earth Elements Administered Intravenously to Rats

“…Cytotoxicity of the light REEs is reported by several researchers to occur in the liver (Sarkander, 1976;Tuchweber et al, 1976) and lungs (Palmer et al, 1987). Why medium and heavy REEs do not induce fatty liver is still unknown.…”

Lanthanides as Anticancer Agents

“…In this aspect, the results also vary with Ln, cells and conditions. As described by Sarkander and Brade, Ln 3+ ions affect RNA synthesis differently, depending on their ionic size [19]. Intracellular Ca 2+ acts as mediator of cell proliferation.…”