Synergism of Nikkomycin Z in Combination with Diphenyl Diselenide Against Sporothrix spp.

We evaluated the in vitro activity of nikkomycin Z (NikZ) in combination with diphenyl diselenide (PhSe)2, two compounds previously shown to have anti-Sporothrix spp. activity. Eighteen isolates of Sporothrix spp. were tested in checkerboard assays. Synergism for inhibition and killing Sporothrix spp. occurred in 100% and 89% of the isolates, respectively. The anti-Sporothrix spp. activity of this combination provides a rationale for in vivo studies to evaluate the application of both compounds in sporotrichosis treatment.

Diphenyl diselenide alone and in combination with itraconazole against Sporothrix schenckii s.str. and Sporothrix globosa.

We evaluated the in vitro susceptibility of Sporothrix schenckii s.str. and Sporothrix globosa to diphenyl diselenide (PhSe)2 alone and in association with itraconazole (ITZ). Eight clinical isolates were tested in microdilution and checkerboard assays. (PhSe)2 alone inhibited all isolates in concentration ≤ 8 µg/mL and was effective in killing one S. schenckii isolate. Inhibitory and fungicidal beneficial effects in its interaction with ITZ were shown against 87.5% (7/8) and 50% (4/8) of the isolates tested, respectively. Our study demonstrates the in vitro antifungal activity of (PhSe)2 against two pathogenic Sporothrix species, suggesting studies of in vivo applications are warranted.

Dopaminergic system contribution to the antidepressant-like effect of 3-phenyl-4-(phenylseleno) isoquinoline in mice.

Depression is a serious disorder characterized by imbalance of mood and emotions, which is accompanied by the reduction in the monoaminergic signaling. The monoamine oxidase inhibition could lead to an increase in monoaminergic neurotransmitter levels in the brain. According to our previous study, 3-phenyl-4-(phenylseleno) isoquinoline (PSI) is a selective and reversible MAO-B inhibitor in vitro. The present study investigated the putative ex vivo inhibitory effect of a single PSI dose on the cerebral MAO activity and its antidepressant-like action in the mouse forced swimming test (FST). Additionally, the dopaminergic system contribution to the antidepressant-like effect of PSI was also evaluated. For this, PSI was dissolved in canola oil to determine time-course (0.5-24 h) and dose-response (25-100 mg/kg, 10 ml/kg, intragastrically) curves of MAO activity inhibition using adult C57Bl/6 male mice. A single PSI dose of 100 mg/kg inhibited the MAO-B activity in the whole brain 8 h after administration to mice, while it did not alter the MAO-A activity. The FST was carried out 0.5, 8, and 24 h after the PSI administration (100 mg/kg) or vehicle, but its antidepressant-like effect was demonstrated only at 0.5 and 8 h after treatment. Lastly, the contribution of dopaminergic system in the PSI antidepressant-like effect was demonstrated by using dopamine receptors antagonists, SCH23390, haloperidol and sulpiride. Thus, a single PSI dose of 100 mg/kg had an antidepressant-like effect in mice subjected to the FST 0.5 and 8 h after its administration. Moreover, the inhibition of cerebral MAO-B activity and modulation of dopamine receptors contributed to the antidepressant-like effect of PSI in mice.

Pattern differences between newborn and adult rats in cisplatin-induced hepatorenal toxicity.

Although cisplatin (CIS) has been associated with serious adverse effects, such as hepatotoxicity and nephrotoxicity in adult rats, there is few reports on its use in newborn rats. The aim of this study was to evaluate acute toxic effects of CIS in newborn rats. Adult and newborn Wistar rats received CIS by the i. p. route, at the dose of 5 or 10 mg/kg. After 24 h of treatment, blood, kidney, and liver were excised from the animals and parameters of renal and hepatic functions, oxidative stress markers were determined. Acute administration of CIS caused an increase of AST activity and urea levels, suggesting hepatorenal toxicity in newborn and adult rats. However, the pattern and intensity of damage was different between ages and tissues. Newborn rats showed more pronouncedly oxidative stress damage, characterized by an increase in reactive species and protein carbonyl levels, lower NPSH content and highest inhibition in δ-ALA-D and CAT activities. Besides that, it was observed a faster molecular response in protein levels involved with apoptosis and oxidative stress response; whereas in the beginning the damage was less severe in the kidney than in the liver of adult rats. Thus, the present study shows that there are body response differences between adult and newborn rats to CIS acute exposure being that newborn rats are more susceptible than adults.