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

• Published in: Advances in redox research : an official journal of the Society for Redox Biology and Medicine and the Society for Free Radical Research-Europe Vol. 10; p. 100092
• Main Authors: Ale, Ebenezer Morayo, Asuelimen, Steve Osagie, Ayo, Victoria Ifeoluwa, Timothy, Mgbede Joy, Umaru, Isaac John, Toluwalase, Ebenezer Kayode
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.04.2024; Elsevier
• Subjects: Antioxidant; Diphenyl diselenide; Glutathione peroxidase; m-trifluoromethyl-diphenyl diselenide; Na+/K+-ATPase; Organoseleniums; Thiols; Glutathione peroxidase; Thiols; Na+/K+-ATPase; m-trifluoromethyl-diphenyl diselenide; Diphenyl diselenide; Organoseleniums; Antioxidant
• ISSN: 2667-1379; 2667-1379
• DOI: 10.1016/j.arres.2023.100092

•m-Trifluoromethyl-diphenyl diselenide (DFDD), a disubstituted diaryl analog of diphenyl diselenide was investigated for the effect of the -CF3 group attachment on the aromatic rings.•Results showed that DFDD utilizes exogenous thiols [dithiol treitol (DTT), cysteine (Cys) and glutathione (GSH)] to reduce hydroperoxides indicating that the compound still possess GPx mimicry property in spite of the -CF3 substituents on its aromatic ring.•DFDD only protected against deoxyribose degradation in the presence of DTT and DFDD also exerted marked (p< 0.05) inhibitory effect on Fe2+or H2O2 or fenton reaction induced lipid peroxidation in rat cerebral tissue homogenate.•DFDD profoundly (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, but the pump activity was not inhibited when the assay was repeated in the presence of DTT or Cys-or GSH indicating that DFDD switched from enzymes's thiols to the oxidation of exogenous thiols in the medium.•In conclusion, the introduction of CF3 group to the aromatic rings of DFDD does not abolish its GPx mimetic and antioxidant properties which still relies on enzymes’ thiols. DFDD could a suitable candidate for eliciting relative pharmacological effect and weak toxicity consequent to the polar nature and high electron withdrawing power conferred by fluorine atoms. However, further research is needed in this regard. 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. [Display omitted]