Sleep recovery ameliorates submandibular salivary gland inflammation associated with paradoxical sleep deprivation in male Wistar rats

Jude Ijuo Abeje; Shehu-Tijani T. Shittu; Olayinka Olawale Asafa; Bimpe Bolarinwa; Taye J. Lasisi

doi:10.1590/1678-7757-2024-0133

Authors

Jude Ijuo Abeje University of Ibadan, College of Medicine, Department of Physiology, Ibadan, Nigeria. https://orcid.org/0000-0002-6296-6252
Shehu-Tijani T. Shittu University of Ibadan, College of Medicine, Department of Physiology, Ibadan, Nigeria. https://orcid.org/0000-0002-7115-1960
Olayinka Olawale Asafa University of Ibadan, College of Medicine, Department of Physiology, Ibadan, Nigeria. https://orcid.org/0000-0001-9043-087X
Bimpe Bolarinwa University of Ibadan, College of Medicine, Department of Physiology, Ibadan, Nigeria.
Taye J. Lasisi University of Ibadan, College of Medicine, Department of Oral Pathology, Ibadan, Nigeria. https://orcid.org/0000-0002-3056-7548

DOI:

https://doi.org/10.1590/1678-7757-2024-0133

Keywords:

Sleep deprivation, Saliva, Inflammation, Cytokines, Submandibular gland

Abstract

Submandibular salivary gland inflammation has been suggested as one of the mechanisms underlying impaired salivary secretion associated with sleep deprivation (SD). However, whether the salivary inflammatory response occurs to the same extent in paradoxical sleep deprivation with or without sleep recovery remains unknown.

Objective: This study evaluated the extent to which inflammation influences salivary impairments associated with paradoxical sleep deprivation with or without sleep recovery.

Methodology: Male Wistar rats were randomly assigned into three groups as control, partial SD (PSD) with sleep recovery for four hours a day and total SD (TSD). Paradoxical SD was carried out for seven days in the SD groups, after which saliva, blood, and submandibular gland samples were taken. Levels of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and nitrite were determined in saliva, serum, and the submandibular salivary gland. Leucocyte count and neutrophil-lymphocyte ratio were determined in all groups. One-way ANOVA and the Tukey's post hoc tests were used for data analysis. P-values < 0.05 were considered statistically significant.

Results: Levels of TNF-α, IL-6, and nitrite in the submandibular salivary glands were significantly higher in the TSD groups (p=0.04,p<0.001, p=0.03, respectively) than in the control. Saliva level of TNF-α was higher in the PSD and TSD groups (p=0.003 and p=0.01 respectively) than in the control. Neutrophil-lymphocyte ratio was significantly higher in both PSD and TSD groups than in the control (p<0.01 for both).

Conclusion: While total SD produced higher inflammatory response in the submandibular salivary gland, four-hour sleep recovery ameliorated this impact. This finding suggests that sleep recovery is crucial to improve inflammatory salivary gland dysfunction induced by sleep deprivation.

Downloads

References

Ersson C, Thorman R, Rodhe Y, Möller L, Hylander B. DNA damage in salivary gland tissue in patients with chronic kidney disease, measured by the comet assay. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112:209-15. doi: 10.1016/j.tripleo.2011.03.016

» https://doi.org/10.1016/j.tripleo.2011.03.016

Lasisi TJ, Shittu ST, Alada AR. Re-establishing normal diet following high fat-diet-induced obesity reverses the altered salivary composition in Wistar rats. J Basic Clin Physiol Pharmacol. 2018;30:111-20. doi: 10.1515/jbcpp-2018-0006

» https://doi.org/10.1515/jbcpp-2018-0006

Lasisi DT; Shittu ST, Meludu CC, Salami AA. Differential effects of total and partial sleep deprivation on salivary factors in Wistar rats. Archives Oral Biol. 2017;73:100-4. doi: 10.1016/j.archoralbio.2016.09.002

» https://doi.org/10.1016/j.archoralbio.2016.09.002

Lasisi TJ, Shittu ST, Abeje JI, Ogunremi KJ, Shittu SA. Paradoxical sleep deprivation induces oxidative stress in the submandibular glands of Wistar rats. J Basic Clin Physiol Pharmacol. 2021;33(4):399-408. doi: 10.1515/jbcpp-2020-0178

» https://doi.org/10.1515/jbcpp-2020-0178

Souza AC, Monico-Neto M, Sueur-Maluf L, Pidone FA, Antunes HK, Ribeiro DA. Inflammatory activity and apoptosis are associated with tissue degeneration in the submandibular gland of rats submitted to paradoxical sleep deprivation. Odontology. 2021;110(2):278-86. doi: 10.1007/s10266-021-00657-6

» https://doi.org/10.1007/s10266-021-00657-6

Khosro S, Alireza S, Omid A, Forough S. Night work and inflammatory markers. Indian J Occupational Environ Med. 2011;15:38-41. doi: 10.4103/0019-5278.82996

» https://doi.org/10.4103/0019-5278.82996

Amano H, Fukuda Y, Yokoo T, Yamaoka K. Interleukin-6 Level among shift and night workers in japan: cross-sectional analysis of the J-HOPE study. J Atheroscler Thromb. 2018;25:1206-14. doi: 10.5551/jat.42036

» https://doi.org/10.5551/jat.42036

Irwin MR, Wang M, Campomayor CO, Collado-Hidalgo A, Cole S. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Inter Med. 2006;166:1756-62. doi: 10.1001/archinte.166.16.1756

» https://doi.org/10.1001/archinte.166.16.1756

Mills PJ, von Känel R, Norman D, Natarajan L, Ziegler MG, Dimsdale JE. Inflammation and sleep in healthy individuals. Sleep. 2007;30:729-35. doi: 10.1093/sleep/30.6.729

» https://doi.org/10.1093/sleep/30.6.729

Kim SW, Jang EC, Kwon SC, Han W, Kang MS, Nam YH, et al. Night shift work and inflammatory markers in male workers aged 20-39 in a display manufacturing company. Annals Occupational Environ Med. 2016;28:48. doi: 10.1186/s40557-016-0135-y

» https://doi.org/10.1186/s40557-016-0135-y

Fahmawi A, Khalifeh M, Alzoubi KH, Rababa'h AM. The effects of acute and chronic sleep deprivation on the immune profile in the rat. Curr Mol Pharmacol. 2023;16(1):101-8. doi: 10.2174/1874467215666220316104321

» https://doi.org/10.2174/1874467215666220316104321

Lasisi TJ, Shittu ST, Oguntokun MM, Tiamiyu NA. Aging affects morphology but not stimulated secretion of saliva in rats. Annals Ib Postgrad Med. 2014;12:109-14.

Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, et al. Impaired immune and acute-phase responses ininterleukin-6-deficient mice. Nature. 1994;368:339-42. doi: 10.1038/368339a0

» https://doi.org/10.1038/368339a0

Ramsay AJ, Husband AJ, Ramshaw IA, Bao S, Matthaei KI, Koehler G, et al. The role of interleukin-6 in mucosal IgA antibody responses in vivo Science. 1994;264:561-3. doi: 10.1126/science.8160012

» https://doi.org/10.1126/science.8160012

Neurath MF, Finotto S. IL-6 signaling in autoimmunity, chronic inflammation and inflammation-associated cancer. Cytokine Growth Factor Rev. 2011;22:83-9. doi: 10.1016/j.cytogfr.2011.02.003

» https://doi.org/10.1016/j.cytogfr.2011.02.003

Leu CM, Wong FH, Chang C, Huang SF, Hu CP. Interleukin-6 acts as an antiapoptotic factor in human esophageal carcinoma cells through the activation of both STAT3 and mitogen-activated protein kinase pathways. Oncogene. 2003;22:7809-18. doi: 10.1038/sj.onc.1207084

» https://doi.org/10.1038/sj.onc.1207084

Fahmi A, Smart N, Punn A, Jabr R, Marber M, Heads R. p42/p44-MAPK and PI3K are sufficient for IL-6 family cytokines/gp130 to signal to hypertrophy and survival in cardiomyocytes in the absence of JAK/STAT activation. Cell Signal. 2013;25:898-909. doi: 10.1016/j.cellsig.2012.12.008

» https://doi.org/10.1016/j.cellsig.2012.12.008

Zhou J, Jin JO, Patel ES, Yu Q. Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions. Cytokine. 2015;76(2):244-52. doi: 10.1016/j.cyto.2015.07.027

» https://doi.org/10.1016/j.cyto.2015.07.027

Azuma M, Motegi K, Aota K, Hayashi Y, Sato M. Role of cytokines in the destruction of acinar structure in Sjögren's syndrome salivary glands. Lab Invest. 1997;77:269-80.

Odusanwo O, Chinthamani S, McCall A, Duffey ME, Baker OJ. Resolvin D1 prevents TNF-alpha-mediated disruption of salivary epithelial formation. Am J Physiol Cell Physiol. 2012;302:1331-45. doi: 10.1152/ajpcell.00207.2011

» https://doi.org/10.1152/ajpcell.00207.2011

Bolstad AI, Eiken HG, Rosenlund B, Alarcon-Riquelme ME, Jonsson R. Increased salivary gland tissue expression of Fas, Fas ligand, cytotoxic T lymphocyte-associated antigen 4, and programmed cell death 1 in primary Sjogren's syndrome. Arthritis Rheum. 2003;48:174-85. doi: 10.1002/art.10734

» https://doi.org/10.1002/art.10734

Raubenheimer K, Bondonno C, Blekkenhorst L, Wagner KH, Peake JM, Neubauer O. Effects of dietary nitrate on inflammation and immune function, and implications for cardiovascular health. Nutr Rev. 2019;77(8):584-99. doi: 10.1093/nutrit/nuz025

» https://doi.org/10.1093/nutrit/nuz025

Goggins MG, Shah SA, Goh J, Cherukuri A, Weir DG, Kelleher D, et al. Increased urinary nitrite, a marker of nitric oxide in active inflammatory bowel disease. Mediators Inflamm. 2001;10:69-73. doi: 10.1080/09629350120054536

» https://doi.org/10.1080/09629350120054536

Wanchu A, Khullar M, Sud A, Bambery P. Elevated nitric oxide production in patients with primary Sjögren's syndrome. Clin Rheumatol. 2000;19:360-64. doi: 10.1007/s100670070028

» https://doi.org/10.1007/s100670070028

Moilanen E, Vapaatalo H. Nitric oxide in inflammation and immune response. Ann Med. 1995;27:359-67. doi: 10.3109/07853899509002589

» https://doi.org/10.3109/07853899509002589

Kim-Shapiro DB, Gladwin MT. Mechanisms of nitrite bioactivation. Nitric Oxide. 2014;38:58-68. doi: 10.1016/j.niox.2013.11.002

» https://doi.org/10.1016/j.niox.2013.11.002

Waltz P, Escobar D, Botero AM, Zuckerbraun BS. Nitrate/Nitrite as critical mediators to limit oxidative injury and inflammation. Antioxid Redox Signal. 2015;23:328-39. doi: 10.1089/ars.2015.6256

» https://doi.org/10.1089/ars.2015.6256

Bryan NS, Fernandez BO, Bauer SM, Garcia-Saura MF, Milsom AB, Rassaf T, et al. Nitrite is a signaling molecule and regulator of gene expression in mammalian tissues. Nat Chem Biol. 2005;1:290-7. doi: 10.1038/nchembio734

» https://doi.org/10.1038/nchembio734

Radi R. Nitric oxide, oxidants, and protein tyrosine nitration. Proc Natl Acad Sci USA. 2004;101:4003-8. doi: 10.1073/pnas.0307446101

» https://doi.org/10.1073/pnas.0307446101

Shearer WT, Reuben JM, Mullington JM, Price NJ, Lee BN, Smith EB, et al. Soluble TNF-α receptor 1 and IL-6 plasma levels in humans subjected to the sleep deprivation model of spaceflight. J Allergy Clin Immunol. 2001;107:165-70. doi: 10.1067/mai.2001.112270

» https://doi.org/10.1067/mai.2001.112270

Frey DJ, Fleshner M, Wright KP Jr. The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun. 2007;21:1050-7. doi: 10.1016/j.bbi.2007.04.003

» https://doi.org/10.1016/j.bbi.2007.04.003

Yamakawa M, Weinstein R, Tsuji T, McBride J, Wong DT, Login GR. Age-related alterations in IL-1beta, TNF-alpha, and IL-6 concentrations in parotid acinar cells from BALB/c and non-obese diabetic mice. J Histochem Cytochem 2000;48:1033-42. doi: 10.1177/002215540004800802

» https://doi.org/10.1177/002215540004800802

Ibáñez-del Valle V, Navarro-Martínez R, Ballestar-Tarín ML, Cauli O. Salivary Inflammatory molecules as biomarkers of sleep alterations: a scoping review. Diagnostics (Basel). 2021;11:278-88. doi: 10.3390/diagnostics11020278

» https://doi.org/10.3390/diagnostics11020278

Zager A, Andersen ML, Ruiz FS, Antunes IB, Tufik S. Effects of acute and chronic sleep loss on immune modulation of rats. Am J Physiol Regul Integr Comp Physiol. 2007;293:R504-9. doi: 10.1152/ajpregu.00105.2007

» https://doi.org/10.1152/ajpregu.00105.2007

Said EA, Al-Abri MA, Al-Saidi I, Al-Balushi MS, Al-Busaidi JZ, Al-Reesi I, et al. Sleep deprivation alters neutrophil functions and levels of Th1-related chemokines and CD4+ T cells in the blood. Sleep Breath. 2019;23:1331-9. doi: 10.1007/s11325-019-01851-1

» https://doi.org/10.1007/s11325-019-01851-1

Sánchez-Alavez M, Conti B, Moroncini G, Criado JR. Contributions of neuronal prion protein on sleep recovery and stress response following sleep deprivation. Brain Res. 2007; 1158:71-80. doi: 10.1016/j.brainres.2007.05.010

» https://doi.org/10.1016/j.brainres.2007.05.010

Oztürk L, Pelin Z, Karadeniz D, Kaynak H, Çakar L, Gözükirmizi E. Effects of 48 hours sleep deprivation on human immune profile. Sleep Res Online. 1999;2:107-11.

Liu J, Yao L, Pan X, Lin P, Haofeng X, Chuansheng L, et al. Neutrophil-to-lymphocyte ratio predicts critical illness patients with 2019 coronavirus disease in the early stage. J Transl Med. 2020;18:1-12. doi: 10.1186/s12967-020-02374-0

» https://doi.org/10.1186/s12967-020-02374-0

Limaye A, Hall BE, Zhang L, Cho A, Prochazkova M, Zheng C, et al. Targeted TNF-α overexpression drives salivary gland inflammation. J Dent Res. 2019;98:713-9. doi: 10.1177/0022034519837240

» https://doi.org/10.1177/0022034519837240

Yamakawa M, Weinstein R, Tsuji T, McBride J, Wong DT, Login GR. Age-related alterations in IL-1beta, TNF-alpha, and IL-6 concentrations in parotid acinar cells from BALB/c and non-obese diabetic mice. J Histochem Cytochem. 2000;48:1033-42. doi: 10.1177/002215540004800802

» https://doi.org/10.1177/002215540004800802

Sleep recovery ameliorates submandibular salivary gland inflammation associated with paradoxical sleep deprivation in male Wistar rats

Authors

DOI:

Keywords:

Abstract

Downloads

References

Downloads

Published

Issue

Section

License

How to Cite

Language

Information

Keywords