XXXV Reunião Anual da SBBqResumoID:2404


Photo-oxidative Damage on Isolated Rat Liver Mitochondria Induced by Phenothiazines
Tiago Rodrigues; Priscila A. de Faria; Felipe S. Pessoto; Carolina G. dos Santos; Iseli L. Nantes

Centro Interdisciplinar de Investigação Bioquímica (CIIB), Universidade de Mogi das Cruzes (UMC), Mogi das Cruzes, SP, Brazil.

The photosensitization is a well-known side effect of phenothiazines and could involve photochemically promoted oxidative damage on mitochondria leading to the impairment of the metabolic functions and apoptosis. In this work, for the first time, we evaluated the effects of photoexcited thioridazine (TR), trifluoperazine (TFP) and fluphenazine (FP) on isolated rat liver mitochondria.  Under irradiation, the investigated phenothiazines led to the lacking of the respiratory control ratio in a dose-dependent manner. These effects were not accompanied by significant swelling and oxidation of protein thiol groups but were accompanied by lipid peroxidation. Lycopene and sorbate, well known scavengers of singlet oxygen and triplet species, respectively, were inefficient to protect mitochondrial lipids against the damage promoted by excited phenothiazines, suggesting that the photochemically produced cation radicals were the oxidant species. In accordance with this proposal, butylated hydroxytoluene (BHT) completely inhibited the lipid peroxidation induced by the UV-irradiation in the presence of phenothiazines. These novel results constitute important contribution for the comprehension of the photochemical properties of phenothiazines in biological systems.