New approaches in education and health sciences management

New approaches in education and health sciences management

The Effect of Swimming Exercise, Diazepam, and Fluoxetine on Serum Corticosterone and Testosterone Levels in Mice Exposed to Lipopolysaccharide

Document Type : Original Article

Authors
Hassan Amouzad Mahdirejei 1
Maghsoud Peeri 1
Mohammad Ali Azarbaijani 1
Forouzan Fattahi Masrour 2
1 Sports Physiology Department, Central Tehran Branch, Islamic Azad University, Tehran, Iran
2 Department of Exercise Physiology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
10.22034/edus.2025.545699.1009
Abstract
Introduction and Objective: Stress and inflammation induced by lipopolysaccharide (LPS) injection can affect the hormonal axis, leading to significant alterations in stress- and sex-related hormones. Identifying effective strategies to modulate these changes has clinical and research importance. Therefore, the aim of this study was to determine the effects of swimming exercise, diazepam, and fluoxetine on serum corticosterone and testosterone levels in mice exposed to LPS.
Methods: In this four-week experimental study, 80 male NMRI mice (aged 80–90 days, weighing 22–25 g) were obtained from the Pasteur Institute of Iran and randomly assigned to eight groups (n=10 per group): (1) control (saline), (2) LPS, (3) swimming + saline, (4) swimming + LPS, (5) diazepam + saline, (6) fluoxetine + saline, (7) swimming + diazepam + LPS, and (8) swimming + fluoxetine + LPS. Diazepam (3 mg/kg) and fluoxetine (10 mg/kg) were administered orally, while exercise groups underwent a four-week swimming protocol. After the interventions, animals received an intraperitoneal injection of either LPS (830 µg/kg) or sterile saline. One-way ANOVA and Tukey’s post hoc test were used for statistical analysis.
Results: LPS administration significantly increased corticosterone and decreased testosterone levels (p<0.05). Combined interventions of swimming with fluoxetine or diazepam were more effective in attenuating these hormonal alterations compared to fluoxetine or diazepam alone (p<0.05).
Conclusion: LPS intervention significantly elevated corticosterone and reduced testosterone levels in mice, indicating a negative impact of inflammatory stress on the hormonal axis. While diazepam and fluoxetine alone could not modulate these effects, their combination with swimming exercise, as well as exercise alone, significantly prevented LPS-induced hormonal alterations.
Keywords
Swimming
Diazepam
Fluoxetine
Corticosterone
Testosterone

Ethics Approval ID: IR.IAU.SARI.REC.1401.146

1.         Ebrahimian F, Najdi N, Masrour FF, Salari AA. Swimming exercise strain-dependently affects maternal care and depression-related behaviors through gestational corticosterone and brain serotonin in postpartum dams. Brain Res Bull. 2022;188:122-130. 10.1016/j.brainresbull.2022.07.020 
2.         André C, Dinel AL, Ferreira G, Layé S, Castanon N. Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation. Brain Behav Immun. 2014;41:10-21. doi: 10.1016/j.bbi.2014.03.012 
3.         Xie J, Geng X, Fan F, Fu X, He S, Li T. The efficacy of therapies for post-stroke depression in aging: An umbrella review. Front Aging Neurosci. 2022;14:993250. 2022 ;2022:2659160. doi: 10.3389/fnagi.2022.993250 
4.         Tutakhail A, Nazari QA, Khabil S, Gardier A, Coudore F. Muscular and mitochondrial effects of long-term fluoxetine treatment in mice, combined with physical endurance exercise on treadmill. Life Sci. 2019;232:116508. doi: 10.1016/j.lfs.2019.05.064 
5.         Russell B, Hrelja KM, Adams WK, Zeeb FD, Taves MD, Kaur S, et al. Differential effects of lipopolysaccharide on cognition, corticosterone and cytokines in socially-housed vs isolated male rats. Behav Brain Res. 2022;433:114000. doi: 10.1016/j.bbr.2022.114000 
6.         Orecchioni M, Ghosheh Y, Pramod AB, Ley K. Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages. Front Immunol. 2019;10:1084. doi: 10.3389/fimmu.2019.01084 
7.         Zolfaghari FS, Pirri F, Gauvin E, Peeri M, Amiri S. Exercise and fluoxetine treatment during adolescence protect against early life stress-induced behavioral abnormalities in adult rats. Pharmacol Biochem Behav. 2021;205:173190. doi: 10.1016/j.pbb.2021.173190 
8.         Loiselle M, Travis F. Improving physical and mental health of college students through Consciousness-Based Education. J Am Coll Health. 2023;71(9):2673-2678. doi: 10.1080/07448481.2021.1984245 
9.         Galgano L, Guidetti GF, Torti M, Canobbio I. The Controversial Role of LPS in Platelet Activation In Vitro. Int J Mol Sci. 2022;23(18):10900. doi: 10.3390/ijms231810900 
10.       Sulakhiya K, Keshavlal GP, Bezbaruah BB, Dwivedi S, Gurjar SS, Munde N, et al. Lipopolysaccharide induced anxiety- and depressive-like behaviour in mice are prevented by chronic pre-treatment of esculetin. Neurosci Lett. 2016;611:106-11. doi: 10.1016/j.neulet.2015.11.031 
11.       Jangra A, Lukhi MM, Sulakhiya K, Baruah CC, Lahkar M. Protective effect of mangiferin against lipopolysaccharide-induced depressive and anxiety-like behaviour in mice. Eur J Pharmacol. 2014;740:337-45. doi: 10.1016/j.ejphar.2014.07.031 
12. Matinfar P, Peeri M, Azarbayjani MA. Swimming exercise attenuates anxiety-like behavior by reducing brain oxidative stress in type 2 diabetic mice. Physiol Behav. 2021;237:113449. doi: 10.1016/j.physbeh.2021.113449 
13. Kosari-Nasab M, Shokouhi G, Ghorbanihaghjo A, Abbasi MM, Salari AA. Anxiolytic- and antidepressant-like effects of Silymarin compared to diazepam and fluoxetine in a mouse model of mild traumatic brain injury. Toxicol Appl Pharmacol. 2018;338:159-173. doi: 10.1016/j.taap.2017.11.012 
14. Bashiri H, Enayati M, Bashiri A, Salari AA. Swimming exercise improves cognitive and behavioral disorders in male NMRI mice with sporadic Alzheimer-like disease. Physiol Behav. 2020;223:113003. doi: 10.1016/j.physbeh.2020.113003 
15.       Amani M, Houwing DJ, Homberg JR, Salari AA. Perinatal fluoxetine dose-dependently affects prenatal stress-induced neurobehavioural abnormalities, HPA-axis functioning and underlying brain alterations in rat dams and their offspring. Reprod Toxicol. 2021;104:27-43. doi: 10.1016/j.reprotox.2021.06.014 
New approaches in education and health sciences management
Volume 2, Issue 2
August 2025
Summer 2025
Pages 1-12

  • Receive Date 26 April 2025
  • Revise Date 06 May 2025
  • Accept Date 26 June 2025
  • First Publish Date 23 July 2025
  • Publish Date 23 July 2025