TY - JOUR
T1 - A pyrazole-containing selenium compound modulates neuroendocrine, oxidative stress, and behavioral responses to acute restraint stress in mice
AU - Birmann, Paloma T.
AU - Domingues, Micaela
AU - Casaril, Angela M.
AU - Smaniotto, Thiago
AU - Hartwig, Daniela
AU - Jacob, Raquel G.
AU - Savegnago, Lucielli
N1 - Funding Information:
The authors are grateful to UFPel and especially to the Programa de Pós Graduação em Biotecnologia (UFPel) for providing support to carry out this work. We would like to thank CNPq , CAPES and FAPERGS (PRONEM 16/2551-0000240-1 ) for the financial support. L.S. and R.G.J. are recipients of CNPq fellowship. This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - Finance Code 001.
Funding Information:
The authors are grateful to UFPel and especially to the Programa de P?s Gradua??o em Biotecnologia (UFPel) for providing support to carry out this work. We would like to thank CNPq, CAPES and FAPERGS (PRONEM 16/2551-0000240-1) for the financial support. L.S. and R.G.J. are recipients of CNPq fellowship. This study was financed in part by the Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - Brasil (CAPES) - Finance Code 001.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - The contribution of oxidative stress has been described in numerous studies as one of the main pathways involved in the pathophysiology of anxiety and its comorbidities, such as chronic pain. Therefore, in this study, we investigated the anxiolytic-like, antiallodynic, and anti-hyperalgesic effects of 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) in response to acute restraint stress (ARS) in mice through the modulation of oxidative stress and neuroendocrine responses. Mice were restrained for 2 h followed by SePy (1 or 10 mg/kg, intragastrically) treatment. Behavioral, and biochemical tests were performed after further 30 min. The treatment with SePy reversed (i) the decreased time spent and the number of entries in the open arms of the elevated plus-maze apparatus, (ii) the decreased time spent in the central zone of the open field test and the increased number of grooming, (iii) the increased number of marbles buried, (iv) the increased response frequency of Von Frey Hair stimulation, and (v) the decreased latency time to nociceptive response in the hot plate test stress induced by ARS. Biochemically, SePy reversed ARS-induced increased levels of plasma corticosterone, and reversed the ARS-induced alterations in the levels of reactive species, lipid peroxidation, and superoxide dismutase and catalase activities in the prefrontal cortices and hippocampi of mice. Moreover, a molecular docking approach suggested that SePy may interact with the active site of the glucocorticoid receptor. Altogether, these results indicate that SePy attenuated anxiolytic-like behavior, hyperalgesia, and mechanical allodynia while modulating oxidative stress and neuroendocrine responses in stressed mice.
AB - The contribution of oxidative stress has been described in numerous studies as one of the main pathways involved in the pathophysiology of anxiety and its comorbidities, such as chronic pain. Therefore, in this study, we investigated the anxiolytic-like, antiallodynic, and anti-hyperalgesic effects of 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazole (SePy) in response to acute restraint stress (ARS) in mice through the modulation of oxidative stress and neuroendocrine responses. Mice were restrained for 2 h followed by SePy (1 or 10 mg/kg, intragastrically) treatment. Behavioral, and biochemical tests were performed after further 30 min. The treatment with SePy reversed (i) the decreased time spent and the number of entries in the open arms of the elevated plus-maze apparatus, (ii) the decreased time spent in the central zone of the open field test and the increased number of grooming, (iii) the increased number of marbles buried, (iv) the increased response frequency of Von Frey Hair stimulation, and (v) the decreased latency time to nociceptive response in the hot plate test stress induced by ARS. Biochemically, SePy reversed ARS-induced increased levels of plasma corticosterone, and reversed the ARS-induced alterations in the levels of reactive species, lipid peroxidation, and superoxide dismutase and catalase activities in the prefrontal cortices and hippocampi of mice. Moreover, a molecular docking approach suggested that SePy may interact with the active site of the glucocorticoid receptor. Altogether, these results indicate that SePy attenuated anxiolytic-like behavior, hyperalgesia, and mechanical allodynia while modulating oxidative stress and neuroendocrine responses in stressed mice.
KW - Anxiety
KW - Mice
KW - Nociception
KW - Pyrazole
KW - Selenium
KW - Stress
UR - http://www.scopus.com/inward/record.url?scp=85090297271&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85090297271&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2020.112874
DO - 10.1016/j.bbr.2020.112874
M3 - Article
C2 - 32835778
AN - SCOPUS:85090297271
SN - 0166-4328
VL - 396
JO - Behavioural Brain Research
JF - Behavioural Brain Research
M1 - 112874
ER -