1,4-Dihydropyridines as Tools for Mitochondrial Medicine Against Oxidative Stress and Associated Metabolic Disorders

Various 1, 4-dihydropyridines (DHPs) could affect basic and cell-type specific mitochondrial functions in different way and at various extent either as protectors or as harmful compounds, depending on their lipophylicity and chemical modifications of the DHP nucleus. Hence, several DHPs may affect: 1) mitochondrial bioenergetics as well as enzymatic activities including electron transport chain reactions and organic acids consumption rate ; 2) mitochondrial lipid peroxidation, production of reactive oxygen species and reactive nitrogen species ; 3) antioxidant enzymes: glutathione-S-transferase, superoxide dismutase, catalase ; 4) mitochondrial and cellular membranotropic and/or physico-chemical properties: incorporation into mitochondrial membrane, alteration of membrane lipid organization, thermotropic phase transition profile and membrane lateral heterogeneity ; 5) chemo-osmotic processes (mitochondrial permeability transition, swelling/contraction/aggregation) ; 6) mitochondrial viability, protecting mitochondria against toxic effects of doxorubicin, MPP+, mixture of rotenone/oligomycin, etc.) ; 7) implication of some DHPs in the regulation of mitochondria-mediated heme biosynthetic pathways was checked also in respect to potential differences between their effects on normal and malignant cells. The effects of DHPs on mitochondria of different cellular origin (hepatic, cardiac, neuronal, brain, muscle) were observed.