Melatonin Decreases the Expression of Inflammation and Apoptosis Markers in the Lung of a Senescence-Accelerated Mice Model
Abstract
Aging is associated with an increase in oxidative stress and inflammation. The aging lung is particularly affected since it is continuously exposed to environmental oxidants while antioxidant machinery weakens with age. Melatonin, a free radical scavenger, counteracts inflammation and apoptosis in healthy cells from several tissues. Its effects on the aging lung are, however, not yet fully understood. This study aimed to investigate the effect of chronic administration of melatonin on the expression of inflammation markers (TNF-α, IL-1β, NFκB2, HO-1) and apoptosis parameters (BAD, BAX, AIF) in the lung tissue of male senescence-accelerated prone mice (SAMP8). In addition, RNA oxidative damage, as the formation of 8-hydroxyguanosine (8-OHG), was also evaluated. Young and old animals, aged 2 and 10 months respectively, were divided into 4 groups: untreated young, untreated old, old mice treated with 1mg/kg/day melatonin, and old animals treated with 10mg/kg/day melatonin. Untreated young and old male senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed. Lungs were collected and immediately frozen in liquid nitrogen. mRNA and protein expressions were measured by RT-PCR and Western blotting, respectively. Levels of 8-OHG were quantified by ELISA. Mean values were analyzed using ANOVA. Old nontreated SAMP8 animals showed increased (p<0.05) mRNA and protein levels of TNF-α, IL-1β, NFκB2, and HO-1 compared to young mice and SAMR1 mice. Melatonin treatment with either dose reversed the aging-derived inflammation (p<0.05). BAD, BAX and AIF expressions also rose with aging, the effect being counteracted with melatonin (p<0.05). Aging also caused a significant elevation (p<0.05) in SAMP8 8-OHG values. This increase was not observed in animals treated with melatonin (p<0.05). In conclusion, melatonin treatment was able to modulate the inflammatory and apoptosis status of the aging lungs, exerting a protective effect on age-induced damage.
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In vivo, melatonin intake diminishes age-derived inflammation and apoptosis, decreases lipid peroxidation, TBARS, and protein carbonyls, counteracting hippocampal senescence and exerting anti-aging and antioxidant effects on mice brains.
“In vivo, melatonin intake has been reported to diminish age-derived inflammation and apoptosis and to decrease lipid peroxidation, thiobarbituric acid reactive substances and protein carbonyls, thus counteracting hippocampal senescence and exerting an anti-aging and antioxidant effect on mice brains [462,463,464,465].”
From The Role of Antioxidants in the Interplay between Oxidative Stress and Senescence (2022) · cites this paper as [462]
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Aging: a theory based on free radical and radiation chemistry
Harman, D. (1956) · Journal of Gerontology · doi:10.1093/geronj/11.3.298 · Cited by 8,567 · see citing works
Oxidative stress, inflammation, and cancer: How are they linked?
Reuter, S., Gupta, S. C., Chaturvedi, M. M., & Aggarwal, B. B. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.09.006 · Cited by 5,441 · see citing works
Cellular and Molecular Immunology
Abbas, A. K., Lichtman, A. H., & Pillai, S. S. (1994) · Cited by 3,571 · see citing works
The Biologic Clock: The Mitochondria?
Harman, D. (1972) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1972.tb00787.x · Cited by 1,991 · see citing works
Harman, D. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.11.7124 · Cited by 1,915 · see citing works
Choi, A. M., & Alam, J. (1996) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.15.1.8679227 · Cited by 1,126 · see citing works
A new murine model of accelerated senescence
Takeda, T., HOSOKAWA, M., TAKESHITA, S., Irino, M., Higuchi, K., Matsushita, T., Tomita, Y., Yasuhira, K., Hamamoto, H., & Shimizu, K. (1981) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(81)90084-1 · Cited by 871 · see citing works
Melatonin: A Multitasking Molecule
Reiter, R. J., Tan, D. X., & Fuentes‐Broto, L. (2010) · Progress in brain research · doi:10.1016/s0079-6123(08)81008-4 · Cited by 642 · see citing works
Superoxide Dismutases in the Lung and Human Lung Diseases
Kinnula, V. L., & Crapo, J. D. (2003) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200212-1479so · Cited by 620 · see citing works
Ageing and the free radical theory
Wickens, A. P. (2001) · Respiration Physiology · doi:10.1016/s0034-5687(01)00313-9 · Cited by 560 · see citing works
Antioxidant Function of Thioredoxin and Glutaredoxin Systems
Holmgren, A. (2000) · Antioxidants and Redox Signaling · doi:10.1089/ars.2000.2.4-811 · Cited by 504 · see citing works
Tan, D. X., Hardeland, R., Manchester, L. C., Paredes, S. D., Korkmaz, A., Sainz, R. M., Mayo, J. C., Fuentes‐Broto, L., & Reiter, R. J. (2009) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1111/j.1469-185x.2009.00118.x · Cited by 365 · see citing works
Self-citationMelatonin signaling and cell protection function
Luchetti, F., Canonico, B., Betti, M., Arcangeletti, M., Pilolli, F., Piroddi, M., Canesi, L., Papa, S., & Galli, F. (2010) · The FASEB Journal · doi:10.1096/fj.10-154450 · Cited by 343 · see citing works
Urata, Y., Honma, S., Goto, S., Todoroki, S., Iida, T., Cho, S., Honma, K., & Kondo, T. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00131-8 · Cited by 333 · see citing works
Butterfield, D. A., & Poon, H. F. (2005) · Experimental Gerontology · doi:10.1016/j.exger.2005.05.007 · Cited by 328 · see citing works
Senescence-accelerated mouse (SAM): a biogerontological resource in aging research
Takeda, T. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00008-1 · Cited by 311 · see citing works
The Inflammation Hypothesis of Aging: Molecular Modulation by Calorie Restriction
Chung, H. Y., Kim, H. J., Kim, J. W., & Yu, B. P. (2001) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2001.tb05662.x · Cited by 305 · see citing works
Heimberg, H., Heremans, Y., Jobin, C., Leemans, R., Cardozo, A. K., Darville, M. I., & Eizirik, D. L. (2001) · Diabetes · doi:10.2337/diabetes.50.10.2219 · Cited by 258 · see citing works
Jou, M., Peng, T.-I., Yu, P., Jou, S., Reiter, R. J., Chen, J., WU, H., Chen, C., & Hsu, L. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2007.00490.x · Cited by 258 · see citing works
The modulatory role of melatonin on immune responsiveness.
Carrillo‐Vico, A., Reiter, R. J., Lardone, P. J., Herrera, J. L., Fernández-Montesinos, R., Guerrero, J. M., & Pozo, D. (2006) · PubMed · Cited by 217 · see citing works
Carbon monoxide and hydrogen sulfide: gaseous messengers in cerebrovascular circulation
Leffler, C. W., Parfenova, H., Jaggar, J. H., & Wang, R. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00793.2005 · Cited by 186 · see citing works
Tha, K. K., Okuma, Y., Miyazaki, H., Murayama, T., Uehara, T., Hatakeyama, R., Hayashi, Y., & Nomura, Y. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02883-3 · Cited by 163 · see citing works
Airway inflammation in chronic obstructive pulmonary disease.
Angelis, N., Porpodis, Κ., Zarogoulidis, P., Spyratos, D., Kioumis, I. P., Papaiwannou, A., Pitsiou, G., Tsakiridis, K., Mpakas, A., Arikas, S., et al. (2014) · Europe PMC (PubMed Central) · doi:10.3978/j.issn.2072-1439.2014.03.07 · Cited by 123 · see citing works
Shin, I., Shin, N., Park, J., Jeon, C., Hong, J., Kwon, O., Kim, J., Lee, I., Kim, J., Oh, S., et al. (2014) · Journal of Pineal Research · doi:10.1111/jpi.12192 · Cited by 113 · see citing works
Basuroy, S., Bhattacharya, S., Tcheranova, D., Qu, Y., Regan, R. F., Leffler, C. W., & Parfenova, H. (2006) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00032.2006 · Cited by 112 · see citing works
Macías, M. J., Escames, G., León, J., Coto‐Montes, A. M., Sbihi, Y., Osuna, A., & Acuña-Castroviejo, D. (2003) · European Journal of Biochemistry · doi:10.1046/j.1432-1033.2003.03430.x · Cited by 100 · see citing works
Self-citationTorres, F., González‐Candia, A., Montt, C., Ebensperger, G., Chubretovic, M., Serón‐Ferré, M., Reyes, R. V., Llanos, A. J., & Herrera, E. A. (2015) · Journal of Pineal Research · doi:10.1111/jpi.12222 · Cited by 85 · see citing works
Skene, D. J., Papagiannidou, E., Hashemi, E., Snelling, J., Lewis, D. F. V., Fernandez, M., & Ioannides, C. (2001) · Journal of Pineal Research · doi:10.1034/j.1600-079x.2001.310408.x · Cited by 85 · see citing works
Melatonin improves inflammation processes in liver of senescence-accelerated prone male mice (SAMP8)
Cuesta‐Sancho, S., Kireev, R. A., Forman, K., Garcı́a, C., Escames, G., Ariznavarreta, C., Vara, E., & Tresguerres, J. A. F. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2010.08.016 · Cited by 78 · see citing works
Self-citationKang, X., Kong, F., Wu, X., Ren, Y., Wu, S., Wu, K., Jiang, Z., & Zhang, W. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000373928 · Cited by 73 · see citing works
Cuesta‐Sancho, S., Kireev, R. A., Garcı́a, C., Rancán, L., Vara, E., & Tresguerres, J. A. F. (2012) · AGE · doi:10.1007/s11357-012-9397-7 · Cited by 67 · see citing works
Self-citationKireev, R. A., Tresguerres, A. C. F., Garcı́a, C., Borrás, C., Ariznavarreta, C., Vara, E., Viña, J., & Tresguerres, J. A. F. (2009) · Biogerontology · doi:10.1007/s10522-009-9242-2 · Cited by 66 · see citing works
Self-citationRadioprotective effect of melatonin on radiation-induced lung injury and lipid peroxidation in rats.
tahamtan, R., Monfared, A. S., Tahamtani, Y., Tavassoli, A., Akmali, M., Mosleh‐Shirazi, M. A., Naghizadeh, M. M., Ghasemi, D., Keshavarz, M., & Haddadi, G. (2015) · PubMed Central · doi:10.22074/cellj.2015.517 · Cited by 63 · see citing works
Kireev, R. A., Vara, E., Viña, J., & Tresguerres, J. A. F. (2014) · AGE · doi:10.1007/s11357-014-9707-3 · Cited by 59 · see citing works
Self-citationCuesta‐Sancho, S., Kireev, R. A., Garcı́a, C., Forman, K., Escames, G., Vara, E., & Tresguerres, J. A. F. (2011) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2011.10.005 · Cited by 56 · see citing works
Self-citationBeneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging
Forman, K., Vara, E., Garcı́a, C., Kireev, R. A., Cuesta‐Sancho, S., Acuña-Castroviejo, D., & Tresguerres, J. A. F. (2010) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2010.00800.x · Cited by 53 · see citing works
Self-citationParedes, S. D., Rancán, L., Kireev, R. A., et al. (2015) · BioResearch open access · doi:10.1089/biores.2015.0032 · Cited by 48 · see citing works
Self-citationMelatonin protects lung mitochondria from aging
Acuña-Castroviejo, D., Carretero, M., Doerrier, C., López, L. C., García‐Corzo, L., Tresguerres, J. A. F., & Escames, G. (2011) · AGE · doi:10.1007/s11357-011-9267-8 · Cited by 46 · see citing works
Self-citationCarosino, C. M., Bein, K. J., Plummer, L. E., et al. (2015) · Journal of Toxicology and Environmental Health · doi:10.1080/15287394.2014.959627 · Cited by 46 · see citing works
Kireev, R. A., Tresguerres, A. C. F., Castillo, C., Salazar, V., Ariznavarreta, C., Vara, E., & Tresguerres, J. A. F. (2006) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00385.x · Cited by 39 · see citing works
Self-citationMelatonin attenuates lung injury in a hind limb ischemia–reperfusion rat model
Takhtfooladi, H. A., Takhtfooladi, M. A., Moayer, F., et al. (2015) · Revista Portuguesa de Pneumologia · doi:10.1016/j.rppnen.2014.01.010 · Cited by 36 · see citing works
Protective actions of melatonin and growth hormone on the aged cardiovascular system
Paredes, S. D., Forman, K., Garcı́a, C., Vara, E., Escames, G., & Tresguerres, J. A. F. (2014) · Hormone Molecular Biology and Clinical Investigation · doi:10.1515/hmbci-2014-0016 · Cited by 30 · see citing works
Self-citationIto, Y., Betsuyaku, T., Moriyama, C., Nasuhara, Y., & Nishimura, M. (2008) · Biogerontology · doi:10.1007/s10522-008-9164-4 · Cited by 27 · see citing works
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Hardeland, R. (2018) · Journal of Pineal Research · doi:10.1111/jpi.12525 · Cited by 455 · see citing works
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Varesi, A., Chirumbolo, S., Campagnoli, L. I. M., Pierella, E., Piccini, G. B., Carrara, A., Ricevuti, G., Scassellati, C., Bonvicini, C., & Pascale, A. (2022) · Antioxidants · doi:10.3390/antiox11071224 · Cited by 145 · see citing works
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- Authors
- Puig, Á., Rancan, L., Paredes, S. D., Carrasco, A., Escames, G., Vara, E., & Tresguerres, J. A. F.
- Affiliations
- Universidad Complutense de Madrid (ES)
- Universidad de Granada (ES)
- Corresponding author
- Tresguerres, Jesús A.F.
- Venue
- Experimental Gerontology
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 75
- Pages
- 1-7
- ISSN
- 0531-5565 (ISSN-L)
- OpenAlex
- W654580105
- Cited by
- 37
- References
- 44
- Citations by year
- 2026: 1 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 7 · 2019: 3 · 2018: 7 · 2017: 7
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Gerontology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Antioxidants, Aging, Portulaca oleracea
- Keywords
- melatonin, lung aging, senescence-accelerated mice, SAMP8 mice, inflammation, apoptosis, oxidative stress, 8-hydroxyguanosine, TNF-α, IL-1β, NF-κB2, heme oxygenase-1, Bad, Bax, AIF, antioxidant defense
- MeSH terms
- Aging, Animals, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Evaluation, Preclinical, Gene Expression Regulation, Lung, Male, Melatonin, Mice, Mutant Strains, Biomarkers, Apoptosis, Oxidative Stress, Inflammation Mediators, Aging, Premature
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