Rh2(CF3CONH)4: The First Biological Assays of a Rhodium (II) Amidate

The rhodium (II) complexes Rh2(tfa)4.2(tfac) and Rh2(tfacam)4 (tfacam = CF3CONH-,tfa = CF3COO-,tfac = CF3CONH2) were synthesized and characterized by microanalysis and electronic and vibrational spectroscopies. Rh2(tfacam)4 was tested both in vitro (U937 and K562 human leukemia cells and Ehrlich ascitic tumor cells) and in vivo for cytostatic activity and lethal dose determination, respectively. This is the first rhodium tetra-amidate to have its biological activity evaluated. The LD50 value for Rh2(tfacam)4 is of the same order as that of cisplatin, and it was verified that the rhodium complex usually needs lower doses than cisplatin to promote the same inhibitory effects

Survival and Histopathological Study of Animals Bearing Ehrlich Tumor Treated With a Rhodium(II) Amidate

The survival of 90% of a tumor-bearing population treated with the complex Rh2 (CF3CONH)4 was examined and the pharmacological parameter Surv90 determined. Histopathological alterations raised for this drug in several tissues were studied in Balb-c mice. A Surv90 dose of 3.8x 10-5 mol/kg was found

Versatility in the biological behavior of two aminobenzoate oxidovanadium (V, IV) compounds. Inhibition or simulation of enzymes

The pharmacological potential of vanadium compounds is of great interest to researchers in treatments of various diseases (diabetes, cancer, tropical endemic diseases, etc.). On the basis of the potential biological/pharmacological applications, in this work we have synthesized and physico-chemically characterized, two new complexes containing vanadium (IV) and (V) with 4-aminobenzoic acid as the ligand (L)

Iron metallodrugs: stability, redox activity and toxicity against Artemia salina.

Iron metallodrugs comprise mineral supplements, anti-hypertensive agents and, more recently, magnetic nanomaterials, with both therapeutic and diagnostic roles. As biologically-active metal compounds, concern has been raised regarding the impact of these compounds when emitted to the environment and associated ecotoxicological effects for the fauna. In this work we assessed the relative stability of several iron compounds (supplements based on glucoheptonate, dextran or glycinate, as well as 3,5,5-trimethylhexanoyl (TMH) derivatives of ferrocene) against high affinity models of biological binding, calcein and aprotransferrin, via a fluorimetric method. Also, the redox-activity of each compound was determined in a physiologically relevant medium. Toxicity toward Artemia salina at different developmental stages was measured, as well as the amount of lipid peroxidation. Our results show that polymer-coated iron metallodrugs are stable, non-redox-active and non-toxic at the concentrations studied (up to 300 µM). However, TMH derivatives of ferrocene were less stable and more redox-active than the parent compound, and TMH-ferrocene displayed toxicity and lipid peroxidation to A. salina, unlike the other compounds. Our results indicate that iron metallodrugs based on polymer coating do not present direct toxicity at low levels of emission; however other iron species (eg. metallocenes), may be deleterious for aquatic organisms. We suggest that ecotoxicity depends more on metal speciation than on the total amount of metal present in the metallodrugs. Future studies with discarded metallodrugs should consider the chemical speciation of the metal present in the composition of the drug

The molecular and cellular basis of iron toxicity in Iron Overload (IO) disorders. Diagnostic and therapeutic approaches

Abnormal iron accumulation in human tissues and oxidative damage are emerging issues in the medical field (1,2). The most commonly recognized type of pathological accumulation has been associated with the general appearance of plasma non-transferrin bound iron (NTBI) (3-16) and particularly with a labile iron component that can infiltrate cells in an unregulated manner (17-19). A major consequence of excess iron accumulation is a rise in cellular labile iron (LCI) (4,8,10) that can promote the formation of reactive oxygenspecies (ROS) from physiological oxygenintermediates (ROI), overriding the cellular antioxidant machineries and causing oxidative damage..

Mechanisms of manganese-induced neurotoxicity in primary neuronal cultures: the role of manganese speciation and cell type

El pdf del artículo es la versión post-print.Manganese (Mn) is an essential trace element required for the proper functioning of a variety of physiological processes. However, chronic exposures to Mn can cause neurotoxicity in humans, especially when it occurs during critical stages of the central nervous system development. The mechanisms mediating this phenomenon as well as the contribution of Mn speciation and the sensitivity of different types of neuronal cells in such toxicity are poorly understood. This study was aimed to investigate the mechanisms mediating the toxic effects of MnCl(2), Mn(II) citrate, Mn(III) citrate, and Mn(III) pyrophosphate in primary cultures of neocortical (CTX) and cerebellar granular (CGC) neurons. Cell viability, mitochondrial function, and glutathione levels were evaluated after Mn exposure. CGC were significantly more susceptible to Mn-induced toxicity when compared with CTX. Moreover, undifferentiated CGC were more vulnerable to Mn toxicity than mature neurons. Mitochondrial dysfunction was observed after the exposure to all the tested Mn species. Ascorbate protected CGC against Mn-induced neurotoxicity, and this event seemed to be related to the dual role of ascorbate in neurons, acting as antioxidant and metabolic energetic supplier. CTX were protected from Mn-induced toxicity by ascorbate only when coincubated with lactate. These findings reinforce and extend the notion of the hazardous effects of Mn toward neuronal cells. In addition, the present results indicate that Mn-induced neurotoxicity is influenced by brain cell types, their origins, and developmental stages as well as by the chemical speciation of Mn, thus providing important information about Mn-induced developmental neurotoxicity and its risk assessment.Spanish Ministries of Health and of Science and Innovation (PI 061212, PI 10/0453); Generalitat of Catalunya (2009/SGR/214); predoctoral and postdoctoral fellowships from the Brazilian São Paulo Research Foundation (FAPESP 06/00001-3 and 09/16018-0 to R.B.H.); a postdoctoral fellowship from the Brazilian National Council for Scientific and Technological Development (CNPq 201362/2007-4 to M.F.).Peer Reviewe

Antioxidant activity and cellular uptake of the hydroxamate-based fungal iron chelators pyridoxatin, desferriastechrome and desferricoprogen

The hydroxamate class of compounds is well known for its pharmacological applications, especially in the context of chelation therapy. In this work we investigate the performance of the fungal hydroxamates pyridoxatin (PYR), desferriastechrome (DAC) and desferricoprogen (DCO) as mitigators of stress caused by iron overload (IO) both in buffered medium and in cells. Desferrioxamine (DFO), the gold standard for IO treatment, was used as comparison. It was observed that all the fungal chelators (in aqueous medium) or PYR and DAC (in cells) are powerful iron scavengers. However only PYR and DCO (in aqueous medium) or PYR (in cells) were also antioxidant against two forms of iron-dependent oxidative stress (ascorbate or peroxide oxidation). These findings reveal that PYR is an interesting alternative to DFO for iron chelation therapy, since it has the advantage of being cell permeable and thus potentially orally active

Concentrations (μM) and percentage of redox-active iron (%) in samples of Fc derivatives (average ± s.d. of 8 measurements).

<p>Total iron concentration = 40 μM.</p><p>^a (p < 0.05)</p><p>^b (p < 0.05)</p><p>^c (p < 0.05)</p><p>Concentrations (μM) and percentage of redox-active iron (%) in samples of Fc derivatives (average ± s.d. of 8 measurements).</p

Quenching of 2 μM calcein in (A) HBS or (B) artificial seawater, and of 2 μM Fl-Tf in (C) HBS or (D) artificial seawater, caused by Fc derivatives.

<p>(E) Percentage of iron available to these probes (chelatable iron), calculated at the highest Fe concentration (2 μM). Rel. un. = relative fluorescence units.</p

Lipid peroxidation (measured as CHP equivalents per gram of <i>A</i>. <i>salina</i>) after the treatment with ferrocene derivatives.

<p>Lipid peroxidation (measured as CHP equivalents per gram of <i>A</i>. <i>salina</i>) after the treatment with ferrocene derivatives.</p