Effect OF m-trifluoromethyl- attachment on the glutathione peroxidase mimicry and antioxidant actions of diphenyl diselenide: Essential thiols of electrogenic sodium pump as a mechanistic component

m-Ditrifluoromethyl-diphenyl diselenide [DFDD (m-CF₃-C₆H₄Se)₂] is a disubstituted diaryl analog of diphenyl diselenide [DPDS (C₆H₅Se)₂] in which a hydrogen atom on each aromatic ring is replaced by trifluoromethyl group (-CF₃). Herein, we investigated the effect of the -CF₃ group introduction on the GPx mimetic and antioxidant properties of DPDS. Animals were euthanized, brains were removed, and used for lipid peroxidation, cerebral sodium pump activity and thiols assays in vitro. Results showed that DFDD utilizes exogenous thiols [dithiol treitol (DTT), cysteine (Cys) and glutathione (GSH)] to reduce hydroperoxides. Furthermore, DFDD only protected against deoxyribose degradation in the presence of DTT. DFDD also exerted marked (p< 0.05) inhibitory effect on Fe²⁺or H₂O₂ or fenton reaction-induced lipid peroxidation in rat cerebral tissue homogenate. In addition, DFDD simultaneously (p< 0.05) inhibited pump activity and lipid peroxidation in cerebral tissue homogenate assaulted with prooxidants with proportionate depletion of thiol in the reaction system. This assay was repeated in the presence of DTT or Cys-or GSH and results revealed that enzyme's activity was not inhibited indicating that DFDD switched from enzymes's thiols to the oxidation of medium's thiols. It is rational to conclude that the introduction of -CF₃ group to the aromatic rings of DFDD does not abolish its GPx mimetic and antioxidant properties and these still rely on thiols of cerebral electrogenic sodium pump. DFDD could be a suitable candidate for relative pharmacological effect and weak toxicity consequent to its possession of high electron withdrawing group. However, further research is needed in this regard.