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4-PSQ reduced mechanical and thermal hypersensitivities of diabetic mice by modulation of oxidative stress and glycemic levels.

In this study, Schiff bases of chitosan (CS) were synthesized using citronellal, citral, and their derivatives containing selenium and sulfur. Organoselenium and organosulfur compounds show attractive biological and pharmaceutical activities, which can be beneficial to CS-based materials. From the characterization analyses, it was found that the CS-derivatives containing organoselenium and organosulfur compounds exhibited the highest conversion degrees (23 and 28%). Biological assays were conducted using films prepared by the blending of CS-derivatives and poly(vinyl alcohol). The antimicrobial evaluation indicated that the film prepared with the sulfur-containing CS was the most active against the tested pathogens (Escherichia coli, Staphylococcus aureus, and Candida albicans) since it reduced considerably their counts (42.5%, 17.4%, and 18.7%). Finally, in vivo assays revealed that this film attenuates atopic dermatitis-like symptoms in mice by suppressing the increase of myeloperoxidase (MPO) activity and reactive species (RS) levels induced by 2,4-dinitrochlorobenzene (DNCB). In summary, CS-derivatives containing chalcogens, mainly organosulfur, are potential candidates for biomedical applications such as for the treatment of chronic skin diseases.

The present study investigated a possible antidepressant-like effect of ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide (BMMS) by using the forced swimming test (FST) and the tail suspension test (TST) in Swiss mice. The contribution of serotoninergic, glutamatergic and nitrergic systems in the antidepressant-like activity of BMMS was evaluated. We also examined the involvement of monoamine oxidase (MAO)-A, MAO-B and Na+, K+-ATPase activities in prefrontal cortex of mice. BMMS, (0.1–10 mg/kg, intragastrically (i.g.)) and fluoxetine (32 mg/kg, i.g.) decreased the immobility time in the FST and TST. The anti-immobility effect of BMMS (10 mg/kg, i.g.) in the TST was prevented by the pretreatment of mice with WAY100635 (0.1 mg/kg, subcutaneously (s.c.), a 5-HT1A receptor antagonist), ketanserin (5 mg/kg, intraperitoneal (i.p.), a 5-HT2A/2C receptor antagonist), and partially blocked by ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist). The anti-immobility effect of BMMS (10 mg / kg, i.g.) was not avoided by pretreatment with MK-801 (0.01 mg/kg, s.c. a non-competitive N-methyl D-Aspartate (NMDA) receptor) in the TST. Pretreatment with L-arginine (500 mg/kg, i.p., a nitric oxide precursor) reversed partially the reduction in the immobility time elicited by BMMS (10 mg/kg, i.g.) in TST. BMMS altered Na+,K+-ATPase and MAO-A activities in prefrontal cortex of mice, but was not able to change the MAO-B activity. In conclusion, BMMS exerted an antidepressant-like effect in mice and serotonergic and nitrergic systems are involved in the antidepressant-like action of compound. BMMS modulated MAO-A and Na+, K+- ATPase activities in prefrontal cortex of mice.

Rationale Depression is often associated with memory impairment, a clinical feature of Alzheimer’s disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system. Objectives The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated. Methods ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1β, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus. Results 4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation. Conclusions These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities.

Wound healing can be a painful and time-consuming process in patients with diabetes mellitus. In light of this, the use of wound healing devices could help to accelerate this process. Here, cellulose-based films loaded with vitamin C (VitC) and/or propolis (Prop), two natural compounds with attractive properties were engineered. The starting materials and the cellulose-based films were characterized in detail. As assessed, vitamin C can be released from the Cel-PVA/VitC and Cel-PVA/VitC/Prop films in a controlled manner. In vitro antibacterial activity studies showed a reduction of bacteria counts (Escherichia coli and Staphylococcus aureus) after Cel-PVA/VitC, Cel-PVA/Prop, and Cel-PVA/VitC/Prop treatments. Moreover, we examined the antibacterial and wound healing properties of the cellulose-based films in a streptozotocin (STZ)-induced diabetic animal model. Diabetic mice exhibited impaired wound healing while the Cel-PVA/VitC/Prop treatment increased the wound closure. A marked reduction in bacterial counts present in the wound environment of diabetic mice was observed after Cel-PVA/VitC, Cel-PVA/Prop and Cel-PVA/VitC/Prop treatment. Histological analysis demonstrated that the non-treated diabetic mice group did not exhibit adequate wound healing while the treated group with Cel-PVA/VitC and Cel-PVA/VitC/Prop films presented good cicatricial response. Furthermore, these novel eco-friendly films may represent a new therapeutic approach to accelerate diabetic wound healing.

This study investigated the effect of the topical treatment with meloxicam-loaded nanocapsules (M-NC) on symptoms, inflammatory response and oxidative parameters in an atopic dermatitis (AD) model in BALB/c mice. 2,4-Dinitrochlorobenzene (DNCB) was applied to the dorsal skin on days 1–3 for sensitization. Mice were challenged with DNCB on the ear (on days 14–29) and dorsal skin (on days 14, 17, 20, 23, 26, and 29). Treatments with blank nanocapsules (B-NC), free meloxicam (M-F) or M-NC were applied to the backs of the mice from days 14 to 29. On the day 30, skin severity scores and scratching behaviour were determined. After that, ears and dorsal skin were removed for determination of inflammatory parameters (edema and myeloperoxidase (MPO) activity) and oxidative parameters (thiobarbituric acid reactive species (TBARS) and non-protein thiol (NPSH) levels), respectively. DNCB increased the severity of skin lesions, scratching behaviour, edema and MPO activity of ears and dorsal skin TBARS levels. M-NC reversed skin severity scores, scratching behaviour and inflammatory response induced by DNCB. B-NC and M-F did not have effect in this model. In summary, meloxicam carried by polymeric nanocapsules reversed inflammatory response and ameliorated symptoms in an AD model.

This study investigated the main effects of the oral treatment with 7-chloro-4-phenylselanyl quinoline (4-PSQ) on symptoms, inflammatory and oxidative parameters in an atopic dermatitis (AD) model in BALB/c mice. In addition, the possibility of antioxidant property of 4-PSQ improves the potential of a biofilm (based on chitosan/poly(vinyl alcohol) (PVA)/ bovine bone powder (BBP)) for the treatment of AD-like skin lesions was evaluated. 2,4-Dinitrochlorobenzene (DNCB) was applied to the dorsal skin on days 1-3 for sensitization. Mice were challenged with DNCB on the ear (on days 14-29) and dorsal skin (on days 14, 17, 20, 23, 26, and 29) and treated with 4-PSQ, dexamethasone, biofilm (biofilm sample without 4-PSQ) or 4-PSQ-loaded biofilms. On the day 30, skin severity scores and scratching behavior were determined. After that, animals were sacrificed, and ears and dorsal skin were removed for determination of inflammatory and oxidative parameters. DNCB induced the skin lesions, scratching behavior and ear swelling, increased myeloperoxidase (MPO) activity (ear and back) and reactive species (RS) levels (back). 4-PSQ, 4-PSQ-loaded biofilms and biofilm treatments ameliorated skin severity scores, scratching behavior and inflammatory response induced by DNCB. 4-PSQ and 4-PSQ-loaded biofilm treatments partially protected against the increase in the RS levels induced by DNCB. Our results revealed that the incorporation of 4-PSQ improved the therapeutic effect of the biofilm. The efficacy of 4-PSQ in treating AD-like lesions was similar or better than dexamethasone. In summary, 4-PSQ has a potential therapeutic advantage in the treatment and management of AD.

Background Atopic dermatitis (AD) is a multifactorial chronic inflammatory disease that affects ∼20 % of children and 3% of adults globally and is generally treated by the topical application of steroidal drugs that have undesirable side-effects. The development of alternative therapies is therefore an important objective. The present study investigated the effects of topical treatment with a novel water-soluble selenium-containing carbohydrate derivative (4-anhydro-4-seleno-D-tatitol, SeTal) on the symptoms and inflammatory parameters in an AD mouse model. Methods Mice were sensitized by applying 2,4-dinitrochlorobenzene (DNCB) to their dorsal skin on days 1–3, then further challenged on their ears and dorsal skin on days 14, 17, 20, 23, 26, and 29. SeTal (1 and 2%) or hydrocortisone (1%) was applied topically to the backs of the mice from days 14–29, and skin severity scores and scratching behavior determined on day 30. The mice were euthanized, and their ears and dorsal skin removed to quantify inflammatory parameters, edema, myeloperoxidase (MPO) activity, and AD-associated cytokines (tumor necrosis factor alpha (TNF-α), interleukins (IL)-18, and IL-33). Results DNCB treatment induced skin lesions and increased the scratching behavior, ear edema, MPO activity (ear and dorsal skin), and cytokine levels in dorsal skin. Topical application of SeTal improved inflammatory markers (cytokine levels and MPO activity), cutaneous severity scores, and scratching behavior. Conclusion The efficacy of SeTal was satisfactory in the analyzed parameters, showing similar or better results than hydrocortisone. SeTal appears to be therapeutically advantageous for the treatment and control of AD.

We describe here a simple method for the synthesis of 6-arylselanylpurines with antioxidant and anticholinesterase activities, and memory improvement effect. This class of compounds was synthesized in good yields by a reaction of 6-chloropurine with diaryl diselenides using NaBH4 as reducing agent and PEG-400 as solvent. Furthermore, the synthesized compounds were evaluated for their in vitro antioxidant and acetylcholinesterase (AChE) inhibitor activities. The best AChE inhibitor was assessed on the in vivo memory improvement. Our results demonstrated that the 6-((4-chlorophenyl)selanyl)-9H-purine and 6-(p-tolylselanyl)-9H-purine presented in vitro antioxidant effect. In addition, 6-((4-fluorophenyl)selanyl)-9H-purine inhibited the AChE activity and improved memory, being a promising therapeutic agent for the treatment of Alzheimer's disease.

The present study was designed to examine the antinociceptive and anti-inflammatory effects of 7-chloro-4-phenylsulfonyl quinoline (PSOQ). Mice were orally (p.o) pretreated with PSOQ (0.01–10 mg/kg), meloxicam (10 mg/kg), 30 min prior to the acetic acid, hot-plate and open field tests. PSOQ reduced abdominal writhing induced by acetic acid, while meloxicam presented no effect. The latency time in the hot-plate test and locomotor/exploratory activities in the open field test were not altered by treatments. In order to evaluate the gastric tolerability after oral administration of PSOQ or meloxicam (10 mg/kg), mice were fasted for 18 h prior to drug exposure. Four hours later, the development of lesions was assessed. PSOQ and meloxicam did not induce ulcer at the dose and time evaluated. Indeed, anti-inflammatory and anti-edematogenic properties of PSOQ were investigated. For this, animals were pretreated with PSOQ (0.01–50 mg/kg; p.o.), meloxicam (50 mg/kg; p.o.), 30 min prior to croton oil application. PSOQ and meloxicam (50 mg/kg) diminished the edema formation and myeloperoxidase activity induced by croton oil in the ear tissue. Taken together these data demonstrated that PSOQ exerts acute anti-inflammatory and antinociceptive actions, suggesting that it may represent an alternative in the development of future new therapeutic strategies.

Vinyl sulfides (a–c), a new class of organosulfur compounds, were screened for antioxidant and antinociceptive activities. In view of this, in vitro antioxidant effect was investigated through the determination of the thiobarbituric acid reactive substances and protein carbonyl levels in rat brain homogenate. Considering the results obtained in vitro, antinociceptive activity of vinyl sulfides (a–c) (5–50 mg/kg, intragastrically) was investigated in a model of nociception induced by glutamate (20 μmol/paw, 20 μl, intraplantar) in mice. A close inspection of the results revealed that unsymmetrical substituted vinyl sulfides (compounds a–c) presented weak antioxidant activity against lipid peroxidation and protein carbonilation in vitro. In vivo experiments showed that compounds a, b, and c, at all doses (5–50 mg/kg), caused an inhibition of the licking and edema induced by glutamate in mice. However, antinociceptive action of sulfides was not dose-dependent, as well as the antioxidant effect was not concentration-dependent. Thus, chemical structure of vinyl sulfides is not related with pharmacological effects. The results demonstrated that vinyl sulfides presented weak antioxidant effect and potent antinociceptive and antiedematogenic effect.

The aim of the present study was to investigate the effects of SCH58261, a selective adenosine A2A receptor antagonist, on striatal toxicity induced by 3-nitropropionic acid (3-NP) in rats. The experimental protocol consisted of 10 administrations (once a day) of SCH58261 (0.01 or 0.05 mg/kg/day, intraperitoneal, i.p.). From 7th to 10th day, 3-NP (20 mg/kg/day, i.p.) was injected 1 h after SCH58261 administration. Twenty-four hours after the last 3-NP injection, the body weight gain, locomotor activity (open-field test), motor coordination (rotarod test), striatal succinate dehydrogenase (SDH) activity and parameters linked to striatal oxidative status were evaluated in rats. The marked body weight loss resulting from 3-NP injections in rats was partially protected by SCH 58261 at both doses. SCH 58261 at the highest dose was effective against impairments on motor coordination and locomotor activity induced by 3-NP. SCH 58261 was unable to restore the inhibition of SDH activity caused by 3-NP. In addition, the increase in striatal reactive species (RS) levels, depletion of reduced glutathione (GSH) content and stimulation of glutathione reductase (GR) activity provoked by 3-NP injections were alleviated by both doses of SCH 58261. The highest dose of SCH 58261 was also effective in attenuating the increase of protein carbonyl levels as well as the inhibition of glutathione peroxidase (GPx) activity in rats exposed to 3-NP. Our results revealed that reduction of oxidative stress in rat striatum by adenosine A2A receptor antagonism contributes for alleviating 3-NP-induced toxicity.

Atopic dermatitis (AD) is the most common chronic inflammatory skin disease with nasty effects on the psychosocial wellbeing of patients. Overall, glucocorticoids, such as hydrocortisone (HC), are the primary pharmacologic drugs used to treat AD and its symptoms. However, the long-term treatment with HC is often accompanied by severe adverse effects. So, this study reports the encapsulation of HC in polymeric films based on gelatin (Gel) and gelatin/starch (Gel/St) and investigates their potential to treat and attenuate 2,4-Dinitrochlorobenzene (DNCB)-induced AD-like symptoms in BALB/c mice model. The prepared films were characterized by different techniques, which indicated that HC was physically entrapped into the polymer matrices. In vitro experiments indicate that the HC release process occurs in a controlled manner (up to 48 h) for both films. Regarding the in vivo experiments, HC-loaded films (Gel@HC and Gel/St@HC), unloaded films (Gel and Gel/St) and HC cream (1%) (as reference) were applied topically on the back of the DNCB-sensitized animals and skin severity scores and scratching behavior were determined. Ex-vivo experiments were done to quantify inflammatory and/or biochemical parameters. As assessed, the topical application of the biopolymeric films (loaded or not with HC) improved the inflammatory parameters, while a lower corticosterone level was observed for the animals treated with Gel and Gel@HC films. In summary, the HC-loaded films showed superior efficiency to treat/attenuate the analyzed parameter than the HC cream (1%). Further, no death or sign of toxicity was observed in animals exposed to HC-loaded films. Thus, the encapsulation of HC in biopolymeric films seems to be a promising alternative for the treatment of injuries caused by chronic skin diseases that require prolonged use of glucocorticoids.

The present study investigated a possible antidepressant-like effect of ((4-tert-butylcyclohexylidene)methyl) (4-methoxystyryl) sulfide (BMMS) by using the forced swimming test (FST) and the tail suspension test (TST) in Swiss mice. The contribution of serotoninergic, glutamatergic and nitrergic systems in the antidepressant-like activity of BMMS was evaluated. We also examined the involvement of monoamine oxidase (MAO)-A, MAO-B and Na

The aim of the present study was to investigate the effects of SCH58261, a selective adenosine A