ABSTRACT
Iron overload, characterized by accumulation of iron in tissues, induces a multiorgan toxicity whose mechanisms are not fully understood. Using cultured cell lines, Caenorhabditis elegans, and mice, we found that ferroptosis occurs in the context of iron-overload-mediated damage. Exogenous oleic acid protected against iron-overload-toxicity in cell culture and Caenorhabditis elegans by suppressing ferroptosis. In mice, oleic acid protected against FAC-induced liver lipid peroxidation and damage. Oleic acid changed the cellular lipid composition, characterized by decreased levels of polyunsaturated fatty acyl phospholipids and decreased levels of ether-linked phospholipids. The protective effect of oleic acid in cells was attenuated by GW6471 (PPAR-α antagonist), as well as in Caenorhabditis elegans lacking the nuclear hormone receptor NHR-49 (a PPAR-α functional homologue). These results highlight ferroptosis as a driver of iron-overload-mediated damage, which is inhibited by oleic acid. This monounsaturated fatty acid represents a potential therapeutic approach to mitigating organ damage in iron overload individuals.
Subject(s)
Ferroptosis , Iron Overload , Animals , Mice , Caenorhabditis elegans , Oleic Acid/pharmacology , Peroxisome Proliferator-Activated Receptors , Iron Overload/drug therapy , Iron , Phospholipid EthersABSTRACT
Neurodegeneration is characterized by loss of neurons causing changes that lead individuals to debilitating conditions; the most common of this condition is the Alzheimer's disease. It has been related that enriched environment (EE) induces experiencedependent plasticity mechanisms, improving the performance of the animals in learning and memory tests. This study evaluated the effects of EE on histological parameters of the cerebellum in rats that received intracerebroventricular streptozotocin. In the standard environment, streptozotocin (STZ) promoted a significant increase between the gaps in the Purkinje layer of approximately 20%. On the other hand, in an enriched environment, the control result (EE) was similar to the result under streptozotocin effect (STZEE). In the standard environment (SE) group a 26% significant reduction in Purkinje cell density was observed under STZ presence. By analyzing the results of the density of Purkinje cells under the effect of streptozotocin in a standard environment (STZSE) against the density of the layer of Purkinje cells also under the effect of streptozotocin in an enriched environment (STZEE), a significant reduction of approximately 76% in density was observed of Purkinje cells in standard environment (STZSE), the mean number of Purkinje cells in enriched environments was not reduced, despite of STZ. According to the results, treatment with STZ and exposure to EE did not change the cerebellum general morphology/cytoarchitecture, hence was no significant difference in the layers thickness. These facts demonstrate that the enriched environment appears to protect the Purkinje cells layer of cerebellum from possible degeneration.
Subject(s)
Alzheimer Disease , Purkinje Cells , Rats , Animals , Streptozocin/toxicity , Cerebellum , Alzheimer Disease/pathologyABSTRACT
A glioblastoma (GBM) is a highly malignant primary brain tumor with a poor prognosis because of its invasiveness and high resistance to current therapies. In GBMs, abnormal glycosylation patterns are associated with malignancy, which allows for the use of lectins as tools for recognition and therapy. More specifically, lectins can interact with glycan structures found on the malignant cell surface. In this context, the present work aimed to investigate the antiglioma potential of ConGF, a lectin purified from Canavalia grandiflora seeds, against C6 cells. The treatment of C6 cells with ConGF impaired the mitochondrial transmembrane potential, reduced cell viability, and induced morphological changes. ConGF also induced massive autophagy, as evaluated by acridine orange (AO) staining and LC3AB-II expression, but without prominent propidium iodide (PI) labeling. The mechanism of action appears to involve the carbohydrate-binding capacity of ConGF, and in silico studies suggested that the lectin can interact with the glycan structures of matrix metalloproteinase 1 (MMP1), a prominent protein found in malignant cells, likely explaining the observed effects.
Subject(s)
Canavalia , Fabaceae , Canavalia/chemistry , Fabaceae/chemistry , Lectins/chemistry , Matrix Metalloproteinase 1 , Propidium , Acridine Orange , Plant Lectins/chemistry , Seeds/chemistry , Carbohydrates/analysisABSTRACT
Plant lectins have been studied owing to their structural properties and biological effects that include agglutinating activity, antidepressant-like effect and antitumor property. The results from this work showed the effects of the lectin extracted from the Dioclea violacea plant (DVL) on the C6 rat glioma cell line. DVL treatment was able to induce caspase-3 activation, apoptotic cell death and cellular membrane damage. Furthermore, DVL decreased mitochondrial membrane potential and increased the number of acidic vesicles and cleavage of LC3, indicating activation of autophagic processes. DVL also significantly inhibited cell migration. Compared to ConA, a well-studied lectin extracted from Canavalia ensiformes seeds, some effects of DVL were more potent, including decreasing C6 glioma cell viability and migration ability. Taken together, the results suggest that DVL can induce glioma cell death, autophagy and inhibition of cell migration, displaying potential anti-glioma activity.
