Effectiveness of diphenyl diselenide against experimental sporotrichosis caused by Sporothrix brasiliensis

Abstract

Diphenyl diselenide (PhSe)2 is a stable organoselenium compound with promising in vitro antifungal activity against several fungi, including Sporothrix brasiliensis. This species is associated with feline and zoonotic sporotrichosis, an emergent mycosis in Latin America. We evaluated the activity of (PhSe)2, alone and in association with itraconazole, in the treatment of sporotrichosis caused by S. brasiliensis, in a murine model. Sixty mice were subcutaneously infected with S. brasiliensis in the footpad and treated by gavage for 30 consecutive days. The six treatment groups received: no active treatment, itraconazole (50 mg/kg), (PhSe)2 at 1, 5, and 10 mg/kg dosages, or itraconazole (50 mg/kg) + (PhSe)2 1 mg/kg, once a day, starting seven days post-inoculation. A significant reduction in the fungal burden of internal organs was achieved in the groups treated with (PhSe)2 1 mg/kg or itraconazole alone in comparison with the untreated group. Higher dosages (5 and 10 mg/kg) of (PhSe)2 increased the clinical manifestation of sporotrichosis and mortality rate. Treatment with both itraconazole and (PhSe)2 1 mg/kg was better than their activities alone (p < 0.001). This is the first demonstration of the potential use of (PhSe)2, alone or with the present drug of choice, in the treatment of sporotrichosis.

Sporothrix brasiliensis: Epidemiology, Therapy, and Recent Developments

“…Only five studies described in vivo tests. Five chemical entities were studied, including buparvaquone (a repurposed drug), silver nanoparticles (AgNPs) with and without chitosan (Chi), two acylhydrazone derivatives (D13 and SB-AF-1002), diphenyl diselenide, and nikkomycin Z [ 50 , 61 , 70 , 71 , 79 ] ( Figure 4 ), in the treatment of experimental sporotrichosis by S. brasiliensis . One drug was tested in an invertebrate model, Galleria mellonella (buparvaquone drug), and four in a murine model, two using C57BL/6 mice and two BALB/cJ.…”

“…At 5 mg/kg, buparvaquone showed similar activity to ITZ regarding fungal burden reduction, and it resulted in a lower mortality rate [ 61 ]. The other four studies describing potential drugs with in vivo activity against sporotrichosis by S. brasiliensis were developed in vertebrate models via a subcutaneous infection of S. brasiliensis yeast cells, followed by 30–35 days of treatment [ 50 , 70 , 71 , 79 ].…”

“…Thus, new options for sporotrichosis treatment, mainly focusing on S. brasiliensis , are urgent. Various in vitro and in vivo studies have described new potential drugs against this Sporothrix species [ 48 , 49 , 50 ]. Chemical drugs are a promising area for research, with data regarding stability and other pharmacological characteristics of the molecules [ 48 , 49 , 50 , 51 , 52 , 53 ].…”

“…Various in vitro and in vivo studies have described new potential drugs against this Sporothrix species [ 48 , 49 , 50 ]. Chemical drugs are a promising area for research, with data regarding stability and other pharmacological characteristics of the molecules [ 48 , 49 , 50 , 51 , 52 , 53 ]. Repurposing drugs are a great strategy to search for new potential antifungals since their pharmacological characteristics are already known, and they ordinarily have demonstrated activity in in vitro tests against S. brasiliensis [ 51 , 52 ].…”

Sporothrix brasiliensis Causing Atypical Sporotrichosis in Brazil: A Systematic Review

“…Meningitis usually follows hematogenous dissemination, mostly in immunosuppressed patients. However, it may also occur in immunocompetent patients as a primary disease with brain involvement, which brings the necessity of in vivo studies to evaluate if some S. brasiliensis strains could have a primary neurological tropism, which has already been described in other fungi such as Cryptococcus neoformans [106,107] and evidenced in in vivo experimental studies [108,109].…”