ABSTRACT
The pathological damage caused by glaucoma is associated to a high intraocular pressure. The ocular hypertone is most likely due to a defective efflux of aqueous humor from the anterior chamber of the eye. Ocular hypertension causes apoptotic death of retinal ganglion cells and overexpression of molecular markers typical of cell stress response and apoptosis. In this work, we report on the neuroprotective, antiapoptotic and antioxidant action of a natural substance, -carnitine. This compound is known for its ability to improve the mitochondrial performance. We analyze a number of cellular and molecular markers, typical of ocular hypertension and, in general, of the cell stress response. In particular, L-carnitine reduces the expression of glial fibrillary acidic protein, inducible nitric oxide synthase, ubiquitin and caspase 3 typical markers of cell stress. In addition, the morphological analysis of the optic nerve evidenced a reduction of the pathological excavation of the optic disk. This experimental hypertone protocol induces a severe lipoperoxidation, which is significantly reduced by L-carnitine. The overall interpretation is that mortality of the retinal cells is due to membrane damage.
Subject(s)
Apoptosis/drug effects , Carnitine/pharmacology , Cell Membrane/pathology , Glaucoma/pathology , Lipid Peroxidation/drug effects , Stress, Physiological/drug effects , Animals , Biomarkers/metabolism , Carnitine/therapeutic use , Cell Membrane/drug effects , Glaucoma/chemically induced , Glaucoma/drug therapy , Male , Optic Disk/drug effects , Optic Disk/pathology , Oxidative Stress/drug effects , Rats , Rats, Wistar , Retina/drug effects , Retina/metabolism , Retina/pathologyABSTRACT
UNLABELLED: Cell proliferation control plays a key role in tumor development. The basic Fibroblast Growth Factor (bFGF), as well as other growth factors, is involved in several pathologies characterized by dysregulation of cell proliferation. In the present work the effects of PD166866, a very potent and selective tyrosine kinase inhibitor were evaluated. Cultured murine fibroblasts (the cell line 3T6) were used to assess the FGFR-1 inhibition mediated by PD166866. Evaluation of cell viability and molecular biology techniques were adopted. PD166866 controls negatively the bFGF/FGFR-1 system thus promoting a significant reduction of cell proliferation and loss of viability in 3T6 cells. The drug possibly controls proliferation via induction of apoptosis as evidenced by a relevant chromatin degradation. CONCLUSION: This study demonstrated that PD166866 might be used in the control of fibrotic proliferative diseases, as well as in other tumor pathologies.
