Disseleneto de bis-(3-amino-2-piridina) melhora a dermatite atópica e os distúrbios psiquiátricos associados regulando o status inflamatório e oxidativo

Abstract

Atopic dermatitis (AD) is a complex and multifactorial pathology. Genetic susceptibility, environmental factors, dysfunction of the skin barrier and dysregulation of the immune system have been implicated in the pathogenesis of AD. This disease negatively affects the physical and mental health of patients, considerably increasing the prevalence of anxiety and depression disorders and accentuating the signs and symptoms of AD. In view of this, the suppressive effect of the bis- (3-amino-2-pyridine) diselenide (BAPD) was investigated in the AD model in BALB/c mice. The animals' dorsal skin was sensitized on days 1-3 through the topical application of 2,4-dinitrochlorobenzene (DNCB). Posteriorly, the mice were challenged with 20 μL of DNCB in the ear and 200 μL in the dorsal skin on days 14, 17, 20, 23, 26 and 29. The animals were treated orally with BAPD (1 or 5 mg/kg) or Dexamethasone (5 mg/kg) from days 14 to 29. The open field test (OFT), elevated plus maze (EPM), tail suspension test (TST), scratching behavior and skin severity scores were determined on day 30. Posteriorly, the animals were euthanized by inhalation of the isoflurane anesthetic and the ears, dorsal skin, hippocampus/cerebral cortex and blood plasma were removed to determine inflammatory parameters (ear edema, myeloperoxidase enzyme (MPO) activity, expression of pro-inflammatory cytokines and histological analysis), oxidative and antioxidant (reactive species (RS), reactive species to thiobarbituric acid (TBARS), levels of non-protein thiol (NPSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST) activity, as well as the levels of corticosterone and Na+ , K+-ATPase enzyme activity. The results of the study demonstrated that DNCB increased the severity of skin lesions, scratching behavior, inflammation and oxidative stress. BAPD (1 and 5 mg/kg) improved cutaneous damage, scratching behavior, and restored MPO enzyme activity in the ear and back of animals induced with DNCB. In addition, the compound reduced levels of expression of tumor necrosis factor (TNF-α), interferon (IFN- γ), interleukin (IL)-33, IL-18, IL-1β, as well as increased expression of IL-10 on the back of the animals. Histological analysis revealed that treatment with BAPD 5 mg/kg reduced the inflammatory response by reducing the infiltration of neutrophils on the back of the mice. The oxidative stress parameters demonstrated that the levels of RS, TBARS and GST enzyme activity increased in animals induced with DNCB. On the other hand, the levels of antioxidant enzymes such as SOD, CAT, GPx, GR and the levels of NPSH were inhibited in these animals. BAPD (1 and 5 mg/kg) was able to attenuate oxidative parameters, in addition to restoring the activity of antioxidant enzymes. Corticosterone levels were reduced only with the dose of 5 mg/kg of the compound. The activity of the enzyme Na+, K+-ATPase in the hippocampus and cerebral cortex decreased in animals exposed to DNCB. Treatment with BAPD (1 and 5 mg/kg) restored Na+, K+-ATPase enzyme activity only in the cerebral cortex. The effectiveness of BAPD was similar or superior to dexamethasone in the evaluated parameters. The data from the present study demonstrated the suppressive effect of BAPD in comorbidity psychiatric disorders - AD regulating inflammatory and oxidative status in mice.