Biology of Metals

The phyto-synthesis of silver nanoparticles and cotton dyeing with natural colorants can reduce the environmental impact of the process considerably. In this study, the extraction of natural colorants from Achillea millefolium petals was optimized by ultrasound technique. The AMP extract was applied for synthesis of silver nanoparticles (Ag NPs) on the cotton fabrics. The dyeing, antibacterial and antioxidant characteristics of cotton samples were investigated to optimize the process and evaluate its efficiency. The AMP extract had good substantivity towards cotton fabrics and the presence of tannic acid, as an environmentally-friendly mordant, further improved the absorption of AMP dye. The antibacterial and antioxidant activities of the dyed samples with AMP extract of were 50%and 60%, respectively. The addition of TA and Ag enhanced the antibacterial and antioxidant activities on the cotton samples to over 99%.

Zinc is known to be indispensable to growth and development and transmission of the genetic message. It does this through a remarkable mosaic of zinc binding motifs that orchestrate all aspects of metabolism. There are now nearly 200 three dimensional structures for zinc proteins, representing all six classes of enzymes and covering a wide range of phyla and species. These structures provide standards of reference for the identity and nature of zinc ligands in other proteins for which only the primary structure is known. Three primary types of zinc sites are apparent from examination of these structures: structural, catalytic and cocatalytic. The most common amino acids that supply ligands to these sites are His, Glu, Asp and Cys. In catalytic sites zinc generally forms complexes with water and any three nitrogen, oxygen and sulfur donors with His being the predominant amino acid chosen. Water is always a ligand to such sites. Structural zinc sites have four protein ligands and no bound water molecule. Cys is the preferred ligand in such sites. Cocatalytic sites contain two or three metals in close proximity with two of the metals bridged by a side chain moiety of a single amino acid residue, such as Asp, Glu or His and sometimes a water molecule. Asp and His are the preferred amino acids for these sites. No Cys ligands are found in such sites. The scaffolding of the zinc sites is also important to the function and reactivity of the bound metal. The influence of zinc on quaternary protein structure has led to the identification of a fourth type of zinc binding site, protein interface. In this case zinc sites are formed from ligands supplied from amino acid residues residing in the binding surface of two proteins. The resulting zinc site usually has the coordination properties of a catalytic or structural zinc binding site.

Cardiovascular complications are among the leading causes of morbidity and mortality in diabetes mellitus (DM). Despite the anti-hyperglycemic effects of various anti-diabetic therapeutic agents like insulin, some of these drugs are implicated in precipitating cardiovascular dysfunction. There is therefore an imperative need to seek alternative drugs that may ameliorate these complications. Accordingly, the aim of the study was to investigate the effects of a dioxidovanadium (V) complex, cis-[VO2(obz)py]) on selected cardiovascular function markers in STZ-induced diabetic rats. The vanadium complex (40 mg kg) was administered orally twice every 3rd day 5 weeks, non-diabetic and diabetic control groups received distilled water whereas the insulin group received subcutaneous insulin injections twice daily for 5 weeks. Blood glucose concentrations, mean arterial pressure (MAP), heart rate, triglycerides (TG) and total cholesterol concentrations were monitored weekly for 5 weeks. Rats were then euthanised and blood and hearts were collected for biochemical analysis. There was a significant decrease in blood glucose, triglycerides, cholesterol concentrations as well as blood pressure of vanadium treated rats compared to the untreated diabetic animals. Vanadium treatment also attenuated cardiac oxidative stress and decreased the expression of transforming growth factor β1 (TGFβ1) and Smad7. Lastly, the administration of the vanadium complex significantly decreased C reactive protein (CRP) and cardiotropin 1(CT-1) concentrations in the plasma and heart tissues. The administration of the dioxidovanadium(V) complex to diabetic rats culminated into cardio-protective effects. Taken together, these observations suggest that this metal complex exhibit a significant potential as an alternative therapeutic drug for DM management.

This work was designed to evaluate the possible changes in glutamate, aspartate, glutamine, GABA and taurine within various hypothalamic areas the striatum and prefrontal cortex after oral cadmium exposure in adult male rats, and if these changes are related to pituitary hormone secretion. The contents of glutamine, glutamate, aspartate, GABA and taurine in the median eminence, anterior, mediobasal and posterior hypothalamus, and in prefrontal cortex in adult male rats exposed to 272.7 μmol l−1 of cadmium chloride (CdCl2) in the drinking water for one month. Cadmium diminished the content of glutamine, glutamate and aspartate in anterior hypothalamus as compared to the values found in the untreated group. Besides, there is a decrease in the content of glutamate, aspartate and taurine in the prefrontal cortex. The amino acids studied did not change in median eminence, mediobasal and posterior hypothalamus or the striatum by cadmium treatment. Plasma prolactin and LH levels decreased in rats exposed to the metal. These results suggest that (1) cadmium differentially affects amino acid content within the brain region studied and (2) the inhibitory effect of cadmium on prolactin and LH secretion may be partially explained by a decrease in the content of both glutamate and aspartate in anterior hypothalamus, but not through changes in GABA and taurine.

The cytotoxic activity of thiosemicarbazones (TSC) and thiocarbohydrazones was investigated against the MelRm melanoma cell line. In general, the melanoma line was susceptible to metal coordinating agents, the most useful of which incorporated the dipyridyl ketone hydrazone sub-structure. The impact of copper supplementation on the cytotoxic activity towards the melanoma line (MelRm) of metal coordinating agents when acting as ionophores is less predictable than the general improvement that has been seen in other cancer cells such as breast adenocarcinoma (MCF-7). The bimetallic nature of thiocarbohydrazone complexes with resultant loss of lipophilicity is a limiting factor in usage against MelRm. The cytotoxic activity of TSC against MelRm when used as copper ionophores could be markedly improved through combination with a partner drug capable of disrupting cellular defences to oxidative stress. In the absence of copper supplementation, both TSC and thiocarbohydrazones could be used to initiate cell cycle arrest and this could be employed to improve cytotoxicity profiles of other metallodrugs such as cisplatin.

A variety of laboratory and clinical investigations during the past 15 years have observed that one of the dangers of excessive iron is its ability to favor animal viral infections. The metal is essential for host cell synthesis of virions and can also impair defense cell function and increase oxidative stress. In both animal models and humans, viral infections cause upregulation of the iron withholding defense system. Factors that suppress the system enhance viral progression; factors that strengthen the system augment host defense. Procedures designed to reinforce the system are being developed and tested; some of these may become useful adjuncts in prevention and management of viral diseases.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematologic disorder characterized by the abnormal proliferation and accumulation of immature B-lymphoblasts arrested at various stages of differentiation. Despite advances in treatment, a significant percentage of pediatric patients with precursor B-ALL still relapse. Therefore, alternative therapies are needed to improve the cure rates for pediatric patients. TPEN (N, N, N’, N’-tetrakis(2-pyridylmethyl)-ethylenediamine) is a pro-oxidant agent capable of selectively inducing apoptosis in leukemia cell lines. Consequently, it has been suggested that TPEN could be a potential agent for oxidative therapy. However, it is not yet known whether TPEN can selectively destroy leukemia cells in a more disease-like model, for example, the bloodstream and bone marrow (BM), ex vivo. This investigation is an extension of a previous study that dealt with the effect of TPEN on ex vivo isolated/purified refractory B-ALL cells. Here, we evaluated the effect of TPEN on whole BM from nonleukemic patients (control) or pediatric patients diagnosed with de novo B-ALL or refractory B-ALL cells by analyzing the hematopoietic cell lineage marker CD34/CD19. Although TPEN was innocuous to nonleukemic BM (n = 3), we found that TPEN significantly induced apoptosis in de novo (n = 5) and refractory B-ALL (n = 6) leukemic cell populations. Moreover, TPEN significantly increased the counts of cells positive for the oxidation of the stress sensor protein DJ-1, a sign of the formation of H2O2, and significantly increased the counts of cells positive for the pro-apoptotic proteins TP53, PUMA, and CASPASE-3 (CASP-3), indicative of apoptosis, in B-ALL cells. We demonstrate that TPEN selectively eliminates B-ALL cells (CD34 + /CD19 +) but no other cell populations in BM (CD34 + /CD19-; CD34-/CD19 + ; CD34-/CD19-) independent of age, diagnosis status (de novo or refractory), sex, karyotype, or immunophenotype. Understanding TPEN-induced cell death in leukemia cells provides insight into more effective therapeutic oxidation-inducing anticancer agents.

The influence of iron, aluminium and of the combined application of both metals on microbial biomass and production of siderophores by three fungi (Aspergillus nidulans, Neurospora crassa and Hymenoscyphus ericae) were investigated. All three species showed a strong iron regulation and Al-sensitivity of siderophore biosynthesis although several differences remained species dependent. Inhibitory effects of Fe and Al on siderophore-production were additive and the higher binding capacity of siderophores towards iron could be compensated by a higher Al-availability. Although pH itself is also important for regulation of siderophore biosynthesis, an indirect effect of Al on siderophore production via an Al-induced pH decrease could be outlined. The toxic effects of Al resulting in a reduced biomass production were compensated by high Fe-availability, whereas the addition of DFAM, a bacterial siderophore, enhanced Al-toxicity.