TY - JOUR
T1 - Putative involvement of sirtuin modulators in LPS-induced sickness behaviour in mice
AU - Kinra, Manas
AU - Ranadive, Niraja
AU - Mudgal, Jayesh
AU - Zhang, Yuqing
AU - Govindula, Anusha
AU - Anoopkumar-Dukie, Shailendra
AU - Davey, Andrew K.
AU - Grant, Gary D.
AU - Nampoothiri, Madhavan
AU - Arora, Devinder
N1 - Funding Information:
“CSIR-Direct SRF Fellowship” to MK and “TMA Pai PhD Scholarship to NR” are truly acknowledged. The authors also thank Dr KSR Pai, Head of Pharmacology Department, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education (MAHE), Manipal, for providing facilities to carry out this project, and Mr Sridhara Prabhu, CARF, MAHE, Manipal for facilitating the animal experiments and providing necessary support to carry out this project.
Funding Information:
Open Access funding enabled and organized by CAUL and its Member Institutions This study was financially supported by Intramural Funding (MCOPS/IMF/2019), MAHE, Manipal to JM and School of Pharmacy & Pharmacology research funds to DA, Griffith University.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/8
Y1 - 2022/8
N2 - NAD+—dependent histone deacetylases (sirtuins 1–7) have been shown to be involved in various pathophysiological conditions including their involvement in cardiovascular, cancerous, neurodegenerative, immune dysregulation and inflammatory conditions. This study investigates the inflammomodulatory potential of resveratrol (RES), a sirtuin activator and sirtinol (SIR), a sirtuin inhibitor in lipopolysaccharide (LPS)-induced model of sickness behaviour in mice. Male Swiss albino mice were divided into five groups (n = 6) consisting of saline (SAL), LPS, RES, SIR, and fluoxetine (FLU) respectively, each group except LPS was prepared by intraperitoneally (i.p.) administration of SAL (10 mL/kg), RES (50 mg/kg), SIR (2 mg/kg) and FLU (10 mg/kg). Thirty minutes after the treatments, all the groups, except SAL were administered LPS (2 mg/kg, i.p.). The behavioural assays including, open field test, forced swim test, and tail suspension tests were conducted 1 h after LPS challenge. LPS administration significantly reduced the locomotor activity along with inducing a state of high immobility and that was prevented by pretreatment with RES and SIR. Further, various proinflammatory cytokines (TNF-α, IL-6, and IL-1β), and oxidative stress markers (MDA and GSH) were found to be significantly elevated in the brain homogenates after LPS treatment. SIR pretreatment abrogated the LPS-induced neuroinflammatory and oxidative stress changes, whereas RES was only effective in reducing the oxidative stress and TNF-α levels. The results of this study speculate that the role of SIRT modulators in neuroinflammatory conditions could vary with their dose, regimen and chemical properties. Further studies with detailed molecular and pharmacokinetic profiling will be needed to explore their therapeutic potentials.
AB - NAD+—dependent histone deacetylases (sirtuins 1–7) have been shown to be involved in various pathophysiological conditions including their involvement in cardiovascular, cancerous, neurodegenerative, immune dysregulation and inflammatory conditions. This study investigates the inflammomodulatory potential of resveratrol (RES), a sirtuin activator and sirtinol (SIR), a sirtuin inhibitor in lipopolysaccharide (LPS)-induced model of sickness behaviour in mice. Male Swiss albino mice were divided into five groups (n = 6) consisting of saline (SAL), LPS, RES, SIR, and fluoxetine (FLU) respectively, each group except LPS was prepared by intraperitoneally (i.p.) administration of SAL (10 mL/kg), RES (50 mg/kg), SIR (2 mg/kg) and FLU (10 mg/kg). Thirty minutes after the treatments, all the groups, except SAL were administered LPS (2 mg/kg, i.p.). The behavioural assays including, open field test, forced swim test, and tail suspension tests were conducted 1 h after LPS challenge. LPS administration significantly reduced the locomotor activity along with inducing a state of high immobility and that was prevented by pretreatment with RES and SIR. Further, various proinflammatory cytokines (TNF-α, IL-6, and IL-1β), and oxidative stress markers (MDA and GSH) were found to be significantly elevated in the brain homogenates after LPS treatment. SIR pretreatment abrogated the LPS-induced neuroinflammatory and oxidative stress changes, whereas RES was only effective in reducing the oxidative stress and TNF-α levels. The results of this study speculate that the role of SIRT modulators in neuroinflammatory conditions could vary with their dose, regimen and chemical properties. Further studies with detailed molecular and pharmacokinetic profiling will be needed to explore their therapeutic potentials.
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U2 - 10.1007/s11011-022-00992-9
DO - 10.1007/s11011-022-00992-9
M3 - Article
C2 - 35554791
AN - SCOPUS:85129885315
SN - 0885-7490
VL - 37
SP - 1969
EP - 1976
JO - Metabolic Brain Disease
JF - Metabolic Brain Disease
IS - 6
ER -