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Received date: 08/05/2025 Published date: 01/07/2025 Case Report

Therapeutic Potentials of Diphenyl Diselenide, A Novel Biomimetic Compound Of Glutathione Peroxidase

Ebenezer Morayo Ale*, Steve Osagie Asuelimen

Department of Biochemistry, Faculty of Pure and Applied Sciences, Federal University Wukari, Taraba State, Nigeria.

*Corresponding author

Ebenezer Morayo Ale; Department of Biochemistry, Faculty of Pure and Applied Sciences, Federal University Wukari, Taraba State, Nigeria.

DOI: 10.55920/JCRMHS.2025.11.001496

Introduction

Diphenyl diselenide (DPDS) is a simple and stable organoselenium molecule with a variety of pharmacological actions (Rosa et al., 2004). In light of numerous fascinating studies on its biological activities, it has now been established as a potentially useful choice for medical application. It is a strong antioxidant compound whose antioxidant efficacy is related to its glutathione peroxidase (GPx) mimicry (Mugesh et al., 2001) and its reported therapeutic activities have been linked to its GPx mimic property.

GPx refers to a class of peroxidase-containing enzymes whose biological function is to shield the body from oxidative damage. Using glutathione (GSH) as a reducing substrate, GPx catalyzes the conversion of a range of hydroperoxides to water (Nogueira and Rocha, 2010). Like the natural enzyme GPx, DPDS interacts with GSH to create intermediate selenol groups. This reaction pattern is identical to that of the active core of natural selenogluthathione peroxidase isoforms. Thus, the selenol-selenolate group that is produced has the ability to degrade hydrogen peroxide and lipid peroxides (Mugesh et al., 2001). DPDS reacts with the thiols to generate a selenenyl sulfide. The selenenyl sulfide reacts with a second equivalent of GSH to yield a selenol intermediate. Finally, the selenol reacts with H₂O₂ or organic hydroperoxide to form H₂O or the respective alcohol (ROH) and ebselen selenenic acid (Mugesh et al., 2001; Mugesh et al., 2004).

Of importance is the fact that DPDS is a better and stronger exogenous antioxidant, when compared with GPx which possesses a binding specificity for GSH. This is consequent to the fact that DPDS can utilize thiols of several sulfhydryl protein and enzymes, including hepatic delta-aminolevulinic acid (δ-ALAD) and (Na⁺/K⁺-ATPase) asides free thiols to effect its GPx mimetic action (Kade etal., 2008; Kade etal., 2011; Kade etal., 2013; Ale et al., 2023a).

Pharmacological Activities of Diphenyl Diselenide

DPDS has attracted great interest owing to its numerous pharmacological properties including antioxidant, neuroprotective, antinociceptive and antidepressant-like actions (Nogueira and Rocha, 2010; Savegnago et al., 2007, 2008a, 2008b).

DPDS has previously been shown to include chemicals with significant and intriguing hepatoprotective effects. For instance, DPDS has been shown to prevent acute liver failure brought on by acetaminophen through its antioxidant action, replenishment of depleted GSH, modifications to cell energy metabolism, and inhibition of mitochondrial dysfunction (Carvalho et al., 2013).

Additionally, DPDS's capacity to fend off radical brain attacks has been studied. By lowering oxidative stress markers, mitochondrial dysfunction, and creatine kinase activity in both early and late stages, intriguing research showed that DPDS was able to lessen the brain dysfunction linked to cecal ligation and perforation-induced sepsis in rats (Silvestre et al., 2014). DPDS also prevented altered mitochondria redox imbalance mediated by ischemia and reperfusion model, which frequently resulted in acute stroke by maintaining mitochondrial redox balance (Dobrachinski et al., 2014).

It has also been observed that DPDS significantly hypoglycemic effect in mouse models of streptozotocin-induced type II diabetes. These diabetic mice also showed an enhanced antioxidant defense system in conjunction with this impact. In the brains of diabetic rats, DPDS likewise corrected redox imbalance and changed the activities of Na⁺/K⁺-ATPase. These findings imply that DPDS may be useful in treating neuronal dysfunction, which frequently coexists with problems related to diabetic hyperglycemia (Kade et al., 2009a).

Conclusively, DPDS has a more potent efficacy to carry out the redox function of GPx owing to the fact that it can utilize proteins’ thiols and thiols from other sources when the cell is depleted of thiol, via the selenol/selenolate groups. Consequently, DPDS may enhance the body's natural defenses against oxidizing agents and offer a novel therapeutic strategy for treating conditions whose etiologies are mediated by oxidative stress (Arteel and Sies, 2001).

Subsequently, there was an open defect at the level of the basal nail wall with exposed bone of the remaining distal phalanx, which was treated with a semi-occlusive bandage, using Tegaderm ^TM Film transparent dressing (see Fig. 2-4).

The patient was then called back for a weekly dressing change. Already two weeks after the start of the occlusive treatment, the previously exposed bone was covered with granulation tissue, with the skin defect still presenting (Fig. 5 + 6). In the absence of discomfort, the foot was released for careful loading according to the child's measures. The follwoing controls showed increasing regeneration of the tip with simultaneous epithelialization (see Fig. 7), so that the semi-occlusive treatment could be ended after 8 weeks.

The final check-up 4 months after the trauma showed a non-irritated, slightly shortened toe with an irregularly growing toenail (see Fig. 8). There was no discomfort, the patient and the parents were very content.

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