Ethel Wilhelm - Academia.edu (original) (raw)
Papers by Ethel Wilhelm
Journal of Applied Toxicology, Sep 14, 2012
ABSTRACTPeroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonists not only improve metabolic... more ABSTRACTPeroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non‐diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR‐γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg–1). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg–1 day–1, per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non‐enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S‐transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin‐induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR‐γ agonists in human application for protecting against drugs‐induced nephrotoxicity. Copyright © 2012 John Wiley & Sons, Ltd.
Chemico-Biological Interactions, Feb 1, 2018
Journal of Essential Oil Research, Sep 25, 2018
Disciplinarum Scientia | Saúde, 2017
Pharmacology, Biochemistry and Behavior, Apr 1, 2022
The present study evaluated the protective effect of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-... more The present study evaluated the protective effect of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) on seizure severity, oxidative stress, and memory disorder in a pentylenetetrazole (PTZ)-kindling model in mice. Male Swiss mice were treated with QTCA-1 (10 mg/kg, intragastrically (i.g.)) or phenobarbital (PHEN) (10 mg/kg; i.g.), 30 min before the injection of PTZ (35 mg/kg, intraperitoneally (i.p.)). Treatments with QCTA-1 or PHEN and PTZ were performed once every 48 h (on the 1st, 3rd, 5th, 7th, 9th and 11th days). After each PTZ injection, the animals were observed for 30 min to assess the stage of seizure intensity. Behavioral parameters were evaluated from the 12th day until the 16th day of the experimental protocol. On the 16th day, mice were euthanized, and the cerebral cortex and hippocampus of mice were removed to determine the thiobarbituric acid reactive species (TBARS) and reactive species (RS) levels, and superoxide dismutase (SOD), Na+/K+-ATPase and acetylcholinesterase (AChE) activities. Our results demonstrated that QTCA-1 significantly decreased the seizure stage score in PTZ-kindled mice. QCTA-1 protected against memory impairment induced by PTZ. QTCA-1 normalized oxidative stress and Na+/K+-ATPase activity in the cerebral structures of PTZ-kindled mice. The effect of QTCA-1 treatment was similar to the positive control used in this study (PHEN). AChE activity did not change in the cerebral structures in PTZ- kindling mice. In conclusion, QCTA-1 may be a promising tool for the treatment of epileptogenesis and epilepsy-associated comorbidity (memory impairment). QCTA-1 to prevent these alterations may involve the reduction of oxidative stress and normalization of Na+/K+-ATPase activity.
Pharmaceuticals
The efficacy of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ) in mitigating paclita... more The efficacy of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ) in mitigating paclitaxel (PTX)-induced peripheral neuropathy was investigated in male and female Swiss mice. The study examined the effects of MTDZ on various pathways, including transient receptor potential cation channel subfamily V member 1 (TRPV1), glutamatergic, nitrergic, guanylate cyclase (cGMP), serotonergic, and opioidergic. Mice received intraperitoneal PTX (2 mg/kg) or vehicle on days 1, 2, and 3, followed by oral MTDZ (1 mg/kg) or vehicle from days 3 to 14. Mechanical and thermal sensitivities were assessed using Von Frey and hot plate tests on days 8, 11, and 14. The open field test evaluated locomotion and exploration on day 12. On day 15, nitrite and nitrate (NOx) levels and Ca2+−ATPase activity in the cerebral cortex and spinal cord were measured after euthanizing the animals. MTDZ administration reversed the heightened mechanical and thermal sensitivities induced by PTX in male and female mi...
This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded... more This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations’ effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstra...
Pharmaceutics
Cu(II) complexes bearing NNO-donor Schiff base ligands (2a, b) have been synthesized and characte... more Cu(II) complexes bearing NNO-donor Schiff base ligands (2a, b) have been synthesized and characterized. The single crystal X-ray analysis of the 2a complex revealed that a mononuclear and a dinuclear complex co-crystallize in the solid state. The electronic structures of the complexes are optimized by Density Functional Theory (DFT) calculations. The monomeric nature of 2a and 2b species is maintained in solution. Antioxidant activities of the ligands (1a, b) and Cu(II) complexes (2a, b) were determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH.) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS+). Our results demonstrated that 2a showed better antioxidant activity. MTT assays were performed to assess the toxicity of ligands and Cu(II) complexes in V79 cells. The antiproliferative activity of compounds was tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and SW620 (colorectal carcinoma) and on MRC-5 ...
New Journal of Chemistry
A new method for the synthesis of benzo[h]quinolines 5-chalcogenyl-functionalized via visible lig... more A new method for the synthesis of benzo[h]quinolines 5-chalcogenyl-functionalized via visible light-promoted intramolecular ortho-cyclization was described. Furthermore, studies have suggested that this class of compounds may have promising therapeutic potential.
Pharmaceutics
In this study a novel gellan gum/pullulan bilayer film containing silibinin-loaded nanocapsules w... more In this study a novel gellan gum/pullulan bilayer film containing silibinin-loaded nanocapsules was developed for topical treatment of atopic dermatitis (AD). The bilayer films were produced by applying a pullulan layer on a gellan gum layer incorporated with silibinin nanocapsules by two-step solvent casting method. The bilayer formation was confirmed by microscopic analysis. In vitro studies showed that pullulan imparts bioadhesitvity for the films and the presence of nanocapsules increased their occlusion factor almost 2-fold. Besides, the nano-based film presented a slow silibinin release and high affinity for cutaneous tissue. Moreover, this film presented high scavenger capacity and non-hemolytic property. In the in vivo study, interestingly, the treatments with vehicle film attenuated the scratching behavior and the ear edema in mice induced by 2,4-dinitrochlorobenzene (DNCB). However, the nano-based film containing silibinin modulated the inflammatory and oxidative parameter...
International Journal for Innovation Education and Research
Alzheimer's disease is a worldwide health issue, and there are currently no treatments that c... more Alzheimer's disease is a worldwide health issue, and there are currently no treatments that can stop this disease. Oxidized graphene derivatives have gained prominence in use in biological systems due to their excellent physical-chemical characteristics, biocompatibility and ability to overcome the blood-brain barrier. Other substances highlighted are those of natural origin from the Amazon biome, such as tucuma, a fruit whose oil has been widely studied in therapeutic applications. Thus, the aim of this study was to investigate the action of graphene oxide, reduced graphene oxide and tucuma oil, isolated and combined, as an alternative for treatment of Alzheimer's disease through studies in silico, in vitro, in vivo and ex vivo. Computational simulation via docking was used to verify the affinity of the substances with the proteins β-amyloid and acetylcholinesterase, in which the reduced graphene oxide was the one that showed the most favorable interaction. The results of t...
No presente trabalho, tracou-se a prevalencia de infeccoes do trato urinario (ITU), o perfil de m... more No presente trabalho, tracou-se a prevalencia de infeccoes do trato urinario (ITU), o perfil de microrganismos causadores e a susceptibilidade dos mesmos frente aos antimicrobianos testados na cidade de Rio Grande/RS. Foi realizada uma analise retrospectiva de laudos de urocultura e urocultura com antibiograma, provenientes de pacientes que utilizaram os servicos de um laboratorio de analises clinicas no periodo de janeiro de 2016 a janeiro de 2017. Os resultados demonstraram que 88,3% das amostras positivas foram oriundas do sexo feminino e 11,7% de pacientes do sexo masculino. Nas mulheres, a faixa etaria mais prevalente foi de 14-40 anos, enquanto nos homens foi maior ou igual a 65 anos. Foi observado que 91,3% das uroculturas positivas sugeriram alguma bacteria Gram negativa, como a Escherichia coli e a Klebsiella pneumoniae, enquanto 8,7% foram relacionadas a bacterias Gram positivas, como o Enterococcus spp. O perfil de susceptibilidade da E. coli e K. pneumonie revelou alta s...
As dislipidemias sao prevalentes em criancas, e as intervencoes nesta idade sao importantes para ... more As dislipidemias sao prevalentes em criancas, e as intervencoes nesta idade sao importantes para a prevencao das doencas cardiovasculares em adultos. O objetivo deste estudo foi realizar uma analise retrospectiva do perfil lipidico de criancas que utilizaram os servicos de diagnostico de um laboratorio de analises clinicas em uma cidade do interior do Rio Grande do Sul (RS), bem como classificar quanto as dislipidemias. Os resultados demonstraram que as concentracoes medias de colesterol total e das lipoproteinas das criancas de 2 a 11 anos encontravam-se ideais, enquanto a media da concentracao de triglicerides encontrava-se acima dos valores de referencia. Para o sexo feminino, a media das concentracoes de colesterol total e colesterol da lipoproteina de baixa densidade (LDL-c) estavam dentro dos valores de referencia, enquanto as concentracoes de triglicerides e colesterol da lipoproteina de alta densidade (HDL-c) encontraram-se acima e abaixo, respectivamente, dos valores preco...
Metabolic Brain Disease, 2021
Alzheimer's disease (AD) is a worldwide problem, and there are currently no treatments that c... more Alzheimer's disease (AD) is a worldwide problem, and there are currently no treatments that can stop this disease. To investigate the binding affinity of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) with acetylcholinesterase (AChE), to verify the effects of FSP in an AD model in mice and to evaluate the toxicological potential of this compound in mice. The binding affinity of FSP with AChE was investigated by molecular docking analyses. The AD model was induced by streptozotocin (STZ) in Swiss mice after FSP treatment (1 mg/kg, intragastrically (i.g.)), 1st-10th day of the experimental protocol. Anxiety was evaluated in an elevated plus maze test, and memory impairment was evaluated in the Y-maze, object recognition and step-down inhibitory avoidance tasks. The cholinergic system was investigated based on by looking at expression and activity of AChE and expression of choline acetyltransferase (ChAT). We evaluated expression and activity of Na+/K+-ATPase. For toxicological analysis, animals received FSP (300 mg/kg, i.g.) and aspartate aminotransferase, alanine aminotransferase activities were determined in plasma and δ-aminolevulinate dehydratase activity in brain and liver. FSP interacts with residues of the AChE active site. FSP mitigated the induction of anxiety and memory impairment caused by STZ. FSP protected cholinergic system dysfunction and reduction of activity and expression of Na+/K+-ATPase. FSP did not modify toxicological parameters evaluated and did not cause the death of mice. FSP protected against anxiety, learning and memory impairment with involvement of the cholinergic system and Na+/K+-ATPase in these actions.
Chemico-Biological Interactions, 2021
Suppressive effect of bis (3-amino-2-pyridine) diselenide (BAPD) on psychiatric disorders - atopi... more Suppressive effect of bis (3-amino-2-pyridine) diselenide (BAPD) on psychiatric disorders - atopic dermatitis (AD) comorbidity in mice was investigated. To sensitize the animals, 2,4-dinitrochlorobenzene (DNCB) was applied to their dorsal skin on days 1-3. Mice were challenged with DNCB on their ears and dorsal skin on days 14, 17, 20, 23, 26, and 29. BAPD and Dexamethasone were administered to the animals, from days 14-29, and skin severity scores and behavioral tests were determined. Oxidative stress and inflammatory parameters were evaluated on the dorsal skin of mice. Na+, K+-ATPase activity and corticosterone levels were determined in hippocampus/cerebral cortex and plasma of mice, respectively. BAPD improved cutaneous damage, scratching behavior, inflammatory and oxidative stress markers. BAPD showed anxiolytic- and antidepressant-like effects and restored Na+, K+-ATPase activity and corticosterone levels. The present study was performed using female mice due the susceptibility for this disease. But, the evaluation of AD model in male mice would help to verify whether the male gender has the same predisposition to present this pathology. Our data demonstrated the suppressive effect of BAPD on psychiatric disorders - AD comorbidity by regulating inflammatory and oxidative status in mice.
International Journal of Pharmaceutics, 2021
This study aimed to prepare pullulan films containing pomegranate seeds oil (PSO) based nanocapsu... more This study aimed to prepare pullulan films containing pomegranate seeds oil (PSO) based nanocapsules, and evaluate the formulation efficacy in the treatment of atopic dermatitis (AD)-like lesions induced by 2,4-dinitrochlorobenzene (DNCB). The Eudragit RS 100® nanocapsules (PSONC) were prepared by the interfacial precipitation of preformed polymer, whereas the films were produced by the solvent casting method. Pomegranate seed oil nanoemulsions (PSONE) were prepared by the spontaneous emulsification method for comparative reasons. Both nanosystems presented adequate mean diameter (248±16 nm for PSONE and 181±6 nm for PSONC), polydispersity index (below 0.2), zeta potential (-25.63±1.1 mV for PSONE and +43.13±0.7 mV for PSONC) and pH in the acid range (6.77±0.27 and 5.31±0.17, PSONE and PSONC). By a pre-formulations study, sorbitol (6.5%) and PEG 400 (1.5%) were considered the most suitable plasticizers for developing pullulan films (6%) intending topical application. In general, pullulan films were classified as flexible and hydrophilic, with high occlusive properties, 57.6±0.8%, 64.6±0.8% for vehicle, PSONCF (pullulan film containing PSONC), respectively. All formulations (films and nanocarriers) presented no irritant potential in the chorioallantoic membrane test. In the in vivo model, the treatments with free PSO and PSONCF attenuated the skin injury as well as the mechanical hypernociceptive behavioral induced by DNCB exposure to mice. Importantly, the biochemical analyses provided evidence that only the treatment with PSONCF modulated the inflammatory and the oxidative stress parameters evaluated in this study. In conclusion, these data lead us to believe that PSONC incorporation into a pullulan film matrix improved the biological properties of the PSO in this AD-model.
ACS Chemical Neuroscience, 2021
Despite major advances, not all patients achieve rheumatoid arthritis (RA) remission, thus highli... more Despite major advances, not all patients achieve rheumatoid arthritis (RA) remission, thus highlighting a pressing need for new therapeutic treatments. Given this scenario, this study sought to evaluate Se-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl] 4-chlorobenzoselenolate (Se-DMC) potential on a complete Freund's adjuvant (CFA)-induced unilateral arthritis model. The effects of Se-DMC (5 mg/kg; oral dose) and meloxicam (5 mg/kg; oral dose), both administered to animals daily for 14 days, on paw edema, mechanical sensitivity, neurobehavioral deficits (anxiogenic- and depressive-like behaviors), Na+/K+-ATPase activity, oxidative stress, and inflammation were evaluated in male Swiss mice exposed to CFA (intraplantar injection of 0.1 mL; 10 mg/mL). Se-DMC reduced the paw withdrawal threshold and CFA-induced paw edema. Histopathological results revealed the antiedematogenic potential of the compound, which was evidenced by lower quantities of dilated lymphatic vessels compared with the CFA group. Se-DMC reduced mRNA relative expression levels of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the hippocampus and paw of CFA mice. The CFA-induced anxiogenic- and depressive-like behaviors were reversed by Se-DMC to the control levels in the elevated plus-maze and tail suspension tests. Se-DMC reduced the paw reactive species levels and restored the superoxide dismutase (hippocampus and paw) and Na+/K+-ATPase (hippocampus) activities previously increased by CFA. Moreover, CFA administration inhibited serum creatinine kinase activity, albeit the Se-DMC effects did not appear to involve the modulation of this enzyme and were equal to or greater than meloxicam. Se-DMC attenuates CFA-induced inflammatory response, nociception, and neurobehavioral deficits in mice.
Applied Organometallic Chemistry, 2020
Functionalization of 2,1,3‐benzothiadiazole (BTD) with thiols at C‐5 position remains low explore... more Functionalization of 2,1,3‐benzothiadiazole (BTD) with thiols at C‐5 position remains low explored. Moreover, the arylthiol‐substitutions at this position are also unexplored and can not be found by a SN2 or SN1 reaction. In this sense, herein we present a new palladium‐catalyzed methodology for a wide variety of unpublished 5‐arylsulfanyl‐benzo‐2,1,3‐thiadiazole derivatives synthesis with moderate to high yields using a low catalytic loading of Pd(L‐Pro)2 as low‐coast, and efficient catalyst in low reaction time. Besides, we concluded that the pKa of thiol species has an important role in this catalysis, mainly in the CMD like catalytic cyclo process, which strongly interferes in the reaction yields. Furthermore, arylsulfanyl‐benzo‐2,1,3‐thiadiazoles derivatives have been assessed (in vitro) as potential acetylcholinesterase inhibitors.
Canadian Journal of Physiology and Pharmacology, 2019
The present study evaluated the in vitro acetylcholinesterase (AChE) inhibitor activity of two ne... more The present study evaluated the in vitro acetylcholinesterase (AChE) inhibitor activity of two new selanyl amide derivatives in cerebral structures of mice. Our results demonstrated that N-(2-(3-(phenylselanyl)propoxy)phenyl)furan-2-carboxamide (1) and N-(2-(3-(phenylselanyl)propoxy)phenyl)thiophene-2-carboxamide (2) inhibited the in vitro AChE activity in mice. Another objective was to assess the effect of the best AChE inhibitor in an amnesic model induced by scopolamine (SCO) in male Swiss mice. The involvement of AChE activity and lipid peroxidation in the cerebral structures was investigated. Our results showed that compound 1 (10 mg/kg, intragastrically) attenuated the latency to find the escape box and the number of holes visited in the Barnes maze task, without altering the locomotor and exploratory activities in an open-field test. Compound 1 protected against increasing in lipid peroxidation levels and AChE activity caused by SCO in the cerebral cortex and hippocampus of m...
Journal of Applied Toxicology, Sep 14, 2012
ABSTRACTPeroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonists not only improve metabolic... more ABSTRACTPeroxisome proliferator‐activated receptor‐γ (PPAR‐γ) agonists not only improve metabolic abnormalities of diabetes and consequent diabetic nephropathy, but they also protect against non‐diabetic kidney disease in experimental models. Here, we investigated the effect of PPAR‐γ agonist pioglitazone against acute renal injury on a cisplatin model in mice. Nephrotoxicity was induced by a single intraperitoneal (i.p.) injection of cisplatin (10 mg kg–1). Pioglitazone was administered for six consecutive days in doses of 15 or 30 mg kg–1 day–1, per os (p.o.), starting 3 days before cisplatin injection. Cisplatin treatment to mice induced a marked renal failure, characterized by a significant increase in serum urea and creatinine levels and alterations in renal tissue architecture. Cisplatin exposure induced oxidative stress as indicated by decreased levels of non‐enzymatic antioxidant defenses [glutathione (GSH) and ascorbic acid levels] and components of the enzymatic antioxidant defenses [superoxide dismutase (SOD), catalase (CAT) glutathione peroxidase (GPx), glutathione reductase (GR) and and glutathione S‐transferase(GST) activities)] in renal tissue. Administration of pioglitazone markedly protected against the increase in urea and creatinine levels and histological alterations in kidney induced by cisplatin treatment. Pioglitazone administration ameliorated GSH and ascorbic acid levels decreased by cisplatin exposure in mice. Pioglitazone protected against the inhibition of CAT, SOD, GPx, GR and GST activities induced by cisplatin in the kidneys of mice. These results indicated that pioglitazone has a protective effect against cisplatin‐induced renal damage in mice. The protection is mediated by preventing the decline of antioxidant status. The results have implications in use of PPAR‐γ agonists in human application for protecting against drugs‐induced nephrotoxicity. Copyright © 2012 John Wiley & Sons, Ltd.
Chemico-Biological Interactions, Feb 1, 2018
Journal of Essential Oil Research, Sep 25, 2018
Disciplinarum Scientia | Saúde, 2017
Pharmacology, Biochemistry and Behavior, Apr 1, 2022
The present study evaluated the protective effect of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-... more The present study evaluated the protective effect of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) on seizure severity, oxidative stress, and memory disorder in a pentylenetetrazole (PTZ)-kindling model in mice. Male Swiss mice were treated with QTCA-1 (10 mg/kg, intragastrically (i.g.)) or phenobarbital (PHEN) (10 mg/kg; i.g.), 30 min before the injection of PTZ (35 mg/kg, intraperitoneally (i.p.)). Treatments with QCTA-1 or PHEN and PTZ were performed once every 48 h (on the 1st, 3rd, 5th, 7th, 9th and 11th days). After each PTZ injection, the animals were observed for 30 min to assess the stage of seizure intensity. Behavioral parameters were evaluated from the 12th day until the 16th day of the experimental protocol. On the 16th day, mice were euthanized, and the cerebral cortex and hippocampus of mice were removed to determine the thiobarbituric acid reactive species (TBARS) and reactive species (RS) levels, and superoxide dismutase (SOD), Na+/K+-ATPase and acetylcholinesterase (AChE) activities. Our results demonstrated that QTCA-1 significantly decreased the seizure stage score in PTZ-kindled mice. QCTA-1 protected against memory impairment induced by PTZ. QTCA-1 normalized oxidative stress and Na+/K+-ATPase activity in the cerebral structures of PTZ-kindled mice. The effect of QTCA-1 treatment was similar to the positive control used in this study (PHEN). AChE activity did not change in the cerebral structures in PTZ- kindling mice. In conclusion, QCTA-1 may be a promising tool for the treatment of epileptogenesis and epilepsy-associated comorbidity (memory impairment). QCTA-1 to prevent these alterations may involve the reduction of oxidative stress and normalization of Na+/K+-ATPase activity.
Pharmaceuticals
The efficacy of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ) in mitigating paclita... more The efficacy of 5-((4-methoxyphenyl)thio)benzo[c][1,2,5] thiodiazole (MTDZ) in mitigating paclitaxel (PTX)-induced peripheral neuropathy was investigated in male and female Swiss mice. The study examined the effects of MTDZ on various pathways, including transient receptor potential cation channel subfamily V member 1 (TRPV1), glutamatergic, nitrergic, guanylate cyclase (cGMP), serotonergic, and opioidergic. Mice received intraperitoneal PTX (2 mg/kg) or vehicle on days 1, 2, and 3, followed by oral MTDZ (1 mg/kg) or vehicle from days 3 to 14. Mechanical and thermal sensitivities were assessed using Von Frey and hot plate tests on days 8, 11, and 14. The open field test evaluated locomotion and exploration on day 12. On day 15, nitrite and nitrate (NOx) levels and Ca2+−ATPase activity in the cerebral cortex and spinal cord were measured after euthanizing the animals. MTDZ administration reversed the heightened mechanical and thermal sensitivities induced by PTX in male and female mi...
This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded... more This study aimed to investigate the action of two different formulations of curcumin (Cur)-loaded nanocapsules (Nc) (Eudragit [EUD] and poly (ɛ-caprolactone) [PCL]) in an amnesia mice model. We also investigated the formulations’ effects on scopolamine-induced (SCO) depressive- and anxiety-like comorbidities, the cholinergic system, oxidative parameters, and inflammatory markers. Male Swiss mice were randomly divided into five groups (n = 8): group I (control), group II (Cur PCL Nc 10 mg/kg), group III (Cur EUD Nc 10 mg/kg), group IV (free Cur 10 mg/kg), and group V (SCO). Treatments with Nc or Cur (free) were performed daily or on alternate days. After 30 min of treatment, the animals received the SCO and were subjected to behavioral tests 30 min later (Barnes maze, open-field, object recognition, elevated plus maze, tail suspension tests, and step-down inhibitory avoidance tasks). The animals were then euthanized and tissue was removed for biochemical assays. Our results demonstra...
Pharmaceutics
Cu(II) complexes bearing NNO-donor Schiff base ligands (2a, b) have been synthesized and characte... more Cu(II) complexes bearing NNO-donor Schiff base ligands (2a, b) have been synthesized and characterized. The single crystal X-ray analysis of the 2a complex revealed that a mononuclear and a dinuclear complex co-crystallize in the solid state. The electronic structures of the complexes are optimized by Density Functional Theory (DFT) calculations. The monomeric nature of 2a and 2b species is maintained in solution. Antioxidant activities of the ligands (1a, b) and Cu(II) complexes (2a, b) were determined by in vitro assays such as 1,1-diphenyl-2-picrylhydrazyl free radicals (DPPH.) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals (ABTS+). Our results demonstrated that 2a showed better antioxidant activity. MTT assays were performed to assess the toxicity of ligands and Cu(II) complexes in V79 cells. The antiproliferative activity of compounds was tested against two human tumor cell lines: MCF-7 (breast adenocarcinoma) and SW620 (colorectal carcinoma) and on MRC-5 ...
New Journal of Chemistry
A new method for the synthesis of benzo[h]quinolines 5-chalcogenyl-functionalized via visible lig... more A new method for the synthesis of benzo[h]quinolines 5-chalcogenyl-functionalized via visible light-promoted intramolecular ortho-cyclization was described. Furthermore, studies have suggested that this class of compounds may have promising therapeutic potential.
Pharmaceutics
In this study a novel gellan gum/pullulan bilayer film containing silibinin-loaded nanocapsules w... more In this study a novel gellan gum/pullulan bilayer film containing silibinin-loaded nanocapsules was developed for topical treatment of atopic dermatitis (AD). The bilayer films were produced by applying a pullulan layer on a gellan gum layer incorporated with silibinin nanocapsules by two-step solvent casting method. The bilayer formation was confirmed by microscopic analysis. In vitro studies showed that pullulan imparts bioadhesitvity for the films and the presence of nanocapsules increased their occlusion factor almost 2-fold. Besides, the nano-based film presented a slow silibinin release and high affinity for cutaneous tissue. Moreover, this film presented high scavenger capacity and non-hemolytic property. In the in vivo study, interestingly, the treatments with vehicle film attenuated the scratching behavior and the ear edema in mice induced by 2,4-dinitrochlorobenzene (DNCB). However, the nano-based film containing silibinin modulated the inflammatory and oxidative parameter...
International Journal for Innovation Education and Research
Alzheimer's disease is a worldwide health issue, and there are currently no treatments that c... more Alzheimer's disease is a worldwide health issue, and there are currently no treatments that can stop this disease. Oxidized graphene derivatives have gained prominence in use in biological systems due to their excellent physical-chemical characteristics, biocompatibility and ability to overcome the blood-brain barrier. Other substances highlighted are those of natural origin from the Amazon biome, such as tucuma, a fruit whose oil has been widely studied in therapeutic applications. Thus, the aim of this study was to investigate the action of graphene oxide, reduced graphene oxide and tucuma oil, isolated and combined, as an alternative for treatment of Alzheimer's disease through studies in silico, in vitro, in vivo and ex vivo. Computational simulation via docking was used to verify the affinity of the substances with the proteins β-amyloid and acetylcholinesterase, in which the reduced graphene oxide was the one that showed the most favorable interaction. The results of t...
No presente trabalho, tracou-se a prevalencia de infeccoes do trato urinario (ITU), o perfil de m... more No presente trabalho, tracou-se a prevalencia de infeccoes do trato urinario (ITU), o perfil de microrganismos causadores e a susceptibilidade dos mesmos frente aos antimicrobianos testados na cidade de Rio Grande/RS. Foi realizada uma analise retrospectiva de laudos de urocultura e urocultura com antibiograma, provenientes de pacientes que utilizaram os servicos de um laboratorio de analises clinicas no periodo de janeiro de 2016 a janeiro de 2017. Os resultados demonstraram que 88,3% das amostras positivas foram oriundas do sexo feminino e 11,7% de pacientes do sexo masculino. Nas mulheres, a faixa etaria mais prevalente foi de 14-40 anos, enquanto nos homens foi maior ou igual a 65 anos. Foi observado que 91,3% das uroculturas positivas sugeriram alguma bacteria Gram negativa, como a Escherichia coli e a Klebsiella pneumoniae, enquanto 8,7% foram relacionadas a bacterias Gram positivas, como o Enterococcus spp. O perfil de susceptibilidade da E. coli e K. pneumonie revelou alta s...
As dislipidemias sao prevalentes em criancas, e as intervencoes nesta idade sao importantes para ... more As dislipidemias sao prevalentes em criancas, e as intervencoes nesta idade sao importantes para a prevencao das doencas cardiovasculares em adultos. O objetivo deste estudo foi realizar uma analise retrospectiva do perfil lipidico de criancas que utilizaram os servicos de diagnostico de um laboratorio de analises clinicas em uma cidade do interior do Rio Grande do Sul (RS), bem como classificar quanto as dislipidemias. Os resultados demonstraram que as concentracoes medias de colesterol total e das lipoproteinas das criancas de 2 a 11 anos encontravam-se ideais, enquanto a media da concentracao de triglicerides encontrava-se acima dos valores de referencia. Para o sexo feminino, a media das concentracoes de colesterol total e colesterol da lipoproteina de baixa densidade (LDL-c) estavam dentro dos valores de referencia, enquanto as concentracoes de triglicerides e colesterol da lipoproteina de alta densidade (HDL-c) encontraram-se acima e abaixo, respectivamente, dos valores preco...
Metabolic Brain Disease, 2021
Alzheimer's disease (AD) is a worldwide problem, and there are currently no treatments that c... more Alzheimer's disease (AD) is a worldwide problem, and there are currently no treatments that can stop this disease. To investigate the binding affinity of 6-((4-fluorophenyl) selanyl)-9H-purine (FSP) with acetylcholinesterase (AChE), to verify the effects of FSP in an AD model in mice and to evaluate the toxicological potential of this compound in mice. The binding affinity of FSP with AChE was investigated by molecular docking analyses. The AD model was induced by streptozotocin (STZ) in Swiss mice after FSP treatment (1 mg/kg, intragastrically (i.g.)), 1st-10th day of the experimental protocol. Anxiety was evaluated in an elevated plus maze test, and memory impairment was evaluated in the Y-maze, object recognition and step-down inhibitory avoidance tasks. The cholinergic system was investigated based on by looking at expression and activity of AChE and expression of choline acetyltransferase (ChAT). We evaluated expression and activity of Na+/K+-ATPase. For toxicological analysis, animals received FSP (300 mg/kg, i.g.) and aspartate aminotransferase, alanine aminotransferase activities were determined in plasma and δ-aminolevulinate dehydratase activity in brain and liver. FSP interacts with residues of the AChE active site. FSP mitigated the induction of anxiety and memory impairment caused by STZ. FSP protected cholinergic system dysfunction and reduction of activity and expression of Na+/K+-ATPase. FSP did not modify toxicological parameters evaluated and did not cause the death of mice. FSP protected against anxiety, learning and memory impairment with involvement of the cholinergic system and Na+/K+-ATPase in these actions.
Chemico-Biological Interactions, 2021
Suppressive effect of bis (3-amino-2-pyridine) diselenide (BAPD) on psychiatric disorders - atopi... more Suppressive effect of bis (3-amino-2-pyridine) diselenide (BAPD) on psychiatric disorders - atopic dermatitis (AD) comorbidity in mice was investigated. To sensitize the animals, 2,4-dinitrochlorobenzene (DNCB) was applied to their dorsal skin on days 1-3. Mice were challenged with DNCB on their ears and dorsal skin on days 14, 17, 20, 23, 26, and 29. BAPD and Dexamethasone were administered to the animals, from days 14-29, and skin severity scores and behavioral tests were determined. Oxidative stress and inflammatory parameters were evaluated on the dorsal skin of mice. Na+, K+-ATPase activity and corticosterone levels were determined in hippocampus/cerebral cortex and plasma of mice, respectively. BAPD improved cutaneous damage, scratching behavior, inflammatory and oxidative stress markers. BAPD showed anxiolytic- and antidepressant-like effects and restored Na+, K+-ATPase activity and corticosterone levels. The present study was performed using female mice due the susceptibility for this disease. But, the evaluation of AD model in male mice would help to verify whether the male gender has the same predisposition to present this pathology. Our data demonstrated the suppressive effect of BAPD on psychiatric disorders - AD comorbidity by regulating inflammatory and oxidative status in mice.
International Journal of Pharmaceutics, 2021
This study aimed to prepare pullulan films containing pomegranate seeds oil (PSO) based nanocapsu... more This study aimed to prepare pullulan films containing pomegranate seeds oil (PSO) based nanocapsules, and evaluate the formulation efficacy in the treatment of atopic dermatitis (AD)-like lesions induced by 2,4-dinitrochlorobenzene (DNCB). The Eudragit RS 100® nanocapsules (PSONC) were prepared by the interfacial precipitation of preformed polymer, whereas the films were produced by the solvent casting method. Pomegranate seed oil nanoemulsions (PSONE) were prepared by the spontaneous emulsification method for comparative reasons. Both nanosystems presented adequate mean diameter (248±16 nm for PSONE and 181±6 nm for PSONC), polydispersity index (below 0.2), zeta potential (-25.63±1.1 mV for PSONE and +43.13±0.7 mV for PSONC) and pH in the acid range (6.77±0.27 and 5.31±0.17, PSONE and PSONC). By a pre-formulations study, sorbitol (6.5%) and PEG 400 (1.5%) were considered the most suitable plasticizers for developing pullulan films (6%) intending topical application. In general, pullulan films were classified as flexible and hydrophilic, with high occlusive properties, 57.6±0.8%, 64.6±0.8% for vehicle, PSONCF (pullulan film containing PSONC), respectively. All formulations (films and nanocarriers) presented no irritant potential in the chorioallantoic membrane test. In the in vivo model, the treatments with free PSO and PSONCF attenuated the skin injury as well as the mechanical hypernociceptive behavioral induced by DNCB exposure to mice. Importantly, the biochemical analyses provided evidence that only the treatment with PSONCF modulated the inflammatory and the oxidative stress parameters evaluated in this study. In conclusion, these data lead us to believe that PSONC incorporation into a pullulan film matrix improved the biological properties of the PSO in this AD-model.
ACS Chemical Neuroscience, 2021
Despite major advances, not all patients achieve rheumatoid arthritis (RA) remission, thus highli... more Despite major advances, not all patients achieve rheumatoid arthritis (RA) remission, thus highlighting a pressing need for new therapeutic treatments. Given this scenario, this study sought to evaluate Se-[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl] 4-chlorobenzoselenolate (Se-DMC) potential on a complete Freund's adjuvant (CFA)-induced unilateral arthritis model. The effects of Se-DMC (5 mg/kg; oral dose) and meloxicam (5 mg/kg; oral dose), both administered to animals daily for 14 days, on paw edema, mechanical sensitivity, neurobehavioral deficits (anxiogenic- and depressive-like behaviors), Na+/K+-ATPase activity, oxidative stress, and inflammation were evaluated in male Swiss mice exposed to CFA (intraplantar injection of 0.1 mL; 10 mg/mL). Se-DMC reduced the paw withdrawal threshold and CFA-induced paw edema. Histopathological results revealed the antiedematogenic potential of the compound, which was evidenced by lower quantities of dilated lymphatic vessels compared with the CFA group. Se-DMC reduced mRNA relative expression levels of tumor necrosis factor-α (TNF-α) and nuclear factor-κB (NF-κB) in the hippocampus and paw of CFA mice. The CFA-induced anxiogenic- and depressive-like behaviors were reversed by Se-DMC to the control levels in the elevated plus-maze and tail suspension tests. Se-DMC reduced the paw reactive species levels and restored the superoxide dismutase (hippocampus and paw) and Na+/K+-ATPase (hippocampus) activities previously increased by CFA. Moreover, CFA administration inhibited serum creatinine kinase activity, albeit the Se-DMC effects did not appear to involve the modulation of this enzyme and were equal to or greater than meloxicam. Se-DMC attenuates CFA-induced inflammatory response, nociception, and neurobehavioral deficits in mice.
Applied Organometallic Chemistry, 2020
Functionalization of 2,1,3‐benzothiadiazole (BTD) with thiols at C‐5 position remains low explore... more Functionalization of 2,1,3‐benzothiadiazole (BTD) with thiols at C‐5 position remains low explored. Moreover, the arylthiol‐substitutions at this position are also unexplored and can not be found by a SN2 or SN1 reaction. In this sense, herein we present a new palladium‐catalyzed methodology for a wide variety of unpublished 5‐arylsulfanyl‐benzo‐2,1,3‐thiadiazole derivatives synthesis with moderate to high yields using a low catalytic loading of Pd(L‐Pro)2 as low‐coast, and efficient catalyst in low reaction time. Besides, we concluded that the pKa of thiol species has an important role in this catalysis, mainly in the CMD like catalytic cyclo process, which strongly interferes in the reaction yields. Furthermore, arylsulfanyl‐benzo‐2,1,3‐thiadiazoles derivatives have been assessed (in vitro) as potential acetylcholinesterase inhibitors.
Canadian Journal of Physiology and Pharmacology, 2019
The present study evaluated the in vitro acetylcholinesterase (AChE) inhibitor activity of two ne... more The present study evaluated the in vitro acetylcholinesterase (AChE) inhibitor activity of two new selanyl amide derivatives in cerebral structures of mice. Our results demonstrated that N-(2-(3-(phenylselanyl)propoxy)phenyl)furan-2-carboxamide (1) and N-(2-(3-(phenylselanyl)propoxy)phenyl)thiophene-2-carboxamide (2) inhibited the in vitro AChE activity in mice. Another objective was to assess the effect of the best AChE inhibitor in an amnesic model induced by scopolamine (SCO) in male Swiss mice. The involvement of AChE activity and lipid peroxidation in the cerebral structures was investigated. Our results showed that compound 1 (10 mg/kg, intragastrically) attenuated the latency to find the escape box and the number of holes visited in the Barnes maze task, without altering the locomotor and exploratory activities in an open-field test. Compound 1 protected against increasing in lipid peroxidation levels and AChE activity caused by SCO in the cerebral cortex and hippocampus of m...