Wang Kui Yang Xiaogai. Safety Issues of Lanthanides-Based Compounds as Diagnostic and Therapeutic Agents as Viewed from Cellular Inorganic Chemistry[J]. Progress in Chemistry, 2009, 21(05): 803-818.
The controversy about the safety issue concerning the agricultural application of lanthanides(Ln) has not yet been completely resolved. In recent years, the scientific basis of the safety in relation to their uses as diagnostic agents and potential drugs has become the research focus. This review proposed several related critical problems in view of the cellular inorganic chemistry and discussed them from the following aspects. First, the role of the solid-phase formation and deposition in biological systems, as in the study of the biological effects of Ln, as well as elucidation of their performance on the clinical pathology, the formation, transformation, distribution and modulation of insoluble compounds have always been involved. Second, issues on the absorption, excretion and accumulation of Ln, especially on whether Ln cross the blood-tissue barriers, it is one of the foci of debate over their toxicity. Third, in the light of the similarity/dissimilarity principle, the common and specific characteristics of biological effects induced by Ln elements have been discussed. Fourth, the signaling pathways involved in the Ln-promoted cell proliferation and apoptosis, as well as the arising problems have been discussed. Based on the above discussions, the key issues faced by the cellular and biological studies on the metal ions or metal-based compounds have been proposed.
Contents
1 Safety issues of lanthanides-based compounds as diagnostic and therapeutic agents
1.1 Gd-based compounds may cause nephrogenic systemic fibrosis(NSF)
1.2 Cerium levels has been related to endomyocardial fibrosis (EMF)
1.3 Debate on the safety of lanthanum carbonate(Fosrenol®)
1.4 About anticancer drug Gd-Motexafin
2 Formation and deposition of solid phases of lanthanide compounds in biological systems
2.1 Precipitation is an inevitable problem in studies on biological effects of lanthanides
2.2 Chemical species of metal compounds under biological conditions
2.3 Chemical essence of transmetallation
3 Absorption, transport and accumulation of lanthanide compounds
3.1 Absorption, transport and accumulation of lanthanide compounds under pathological conditions
3.2 Whether Ln can cross blood-tissue barriers under pathological conditions?
4 How to explain the differential biological effects among lanthanides?
4.1 Similarity/dissimilarity principle for lanthanides induced biological effects
4.2 Diversity among lanthanides
5 Mechanism underlying lanthanides-promoted proliferation and apoptosis, as well as the arising problems
5.1 Is lanthanides' action a hormetic effect?
5.2 Whether lanthanides-induced apoptosis effect can be used for cancer treatment?
5.3 Possible signal transduction pathways involved in lanthanides-induced cell proliferation and apoptosis
5.4 May lanthanides-promoted proliferation trigger carcinogenic or mutagenic effects?
6 Concluding remarks