Neurorescue by a ROS Decomposition Catalyst.

The effect of the bis-sulfonated iron(III) corrole (1-Fe), a potent decomposition catalyst of reactive oxygen species, on rescuing SN4741 cells that were damaged by 6-hydroxydopamine (6-OHDA) was investigated as an in vitro model system for studying cell death of dopaminergic neurons in the substantia nigra. Important findings that accompanied the ability to rescue dopaminergic neurons were increased expression of phenotypic dopaminergic proteins, such as tyrosine hydroxylase (TH) and dopamine transporter (DAT), which were significantly depleted upon 6-OHDA-mediated damage. 1-Fe also elevated expression levels of aldehyde dehydrogenase 1 (ALDH-1), previously disclosed as a cardinal protein in the pathogenesis of Parkinson's disease. Since these findings suggested that 1-Fe affects quite a wide range of intracellular mechanisms, vital intracellular pathways that involve neuroplasticity, growth, differentiation and survival of neurons, were examined. Phosphatidylinositol 3-kinase (PI3K) and protein kinase c (PKC) were found to be involved, as pharmacological inhibitors of these kinases abolished the neurorescue effect of 1-Fe. 1-Fe also elevated the expression of antiapoptotic protein Bcl-2, which is essential for proper mitochondrial function and cellular survival. The overall conclusion is that 1-Fe is capable of rescuing already damaged neuronal cells by a variety of mechanisms that are beyond its antioxidant activity.

Photodynamic inactivation of mold fungi spores by newly developed charged corroles.

The photodynamic effect, originally used in photodynamic therapy (PDT) for the treatment of different diseases, e.g. of cancer, has recently been introduced for the inactivation of bacteria. Mold fungi, which provoke health problems like allergies and diseases of the respiratory tract, are even more resistant and their biology is also very different. This study presents the development of four new photosensitizers, which, in combination with low doses of white light, inhibit the germination of mold fungi spores. Two of them even cause lethal damage to the conidia (spores) which are responsible for the spreading of mold fungi. The photoactivity of the newly synthesized corroles was obtained by their application on three different mold fungi: Aspergillus niger, Cladosporium cladosporoides, and Penicillium purpurgenum. To distinguish between inactivation of germination and permanent damage, the fungi were first incubated under illumination for examination of photosensitizer-induced growth inhibition and then left in darkness to test the survival of the conidia. None of the compounds displayed dark toxicity, but all of them attenuated or prevented germination when exposed to light, and the positively charged complexes induced a complete damage of the conidia.

Combating diabetes complications by 1-Fe, a corrole-based catalytic antioxidant.

The potent corrole-based ROS/RNS decomposition catalyst 1-Fe was examined regarding its effect on the development of diabetes complications, in parallel with studies that addressed safety and toxicity issues that are crucial for forwarding the compound towards clinical trials. Cardiotoxicity and mutagenic potential were addressed by applying the hERG and AMES tests on 1-Fe, revealing that it is safe enough for further development. General toxicity studies in rats disclosed the appearance of mild adverse effect only at a dose of 300 mg/kg/day. In the streptozotocin-induced rat model of diabetes, 20 mg/kg/day 1-Fe prevented cataract incidents and reduced its severity, displayed a favorable effect on kidney function, and also decreased serum cholesterol and triglyceride levels. Comparisons with alpha lipoic acid, a compound with reported benefits in the same mouse model, indicate that the benefits of 1-Fe are due to the combination of its ability to disarm ROS/RNS and its positive effect on lipid profile.