Aralıklı Oruç ve Probiyotik Kullanımının Yaşlanan Akciğerlerde Oksidatif Stres ve Moleküler Değişiklikler Üzerindeki Koruyucu Etkileri

Year 2025, Volume: 26 Issue: 1, 1 - 11, 20.03.2025

Burcu Baba , Dilek Yonar , Hikmet Taner Teker , Taha Ceylani

https://doi.org/10.69601/meandrosmdj.1583374

Abstract

Amaç: Yaşlanma, özellikle akciğerlerde artan oksidatif stres ve azalan hücresel onarım mekanizmalarıyla ilişkilidir. Bu çalışma, aralıklı orucun (IF), SCD Probiyotiklerinin ve bunların kombinasyonunun yaşlanan sıçanların akciğerlerindeki oksidatif stres ve moleküler değişiklikler üzerindeki koruyucu etkilerini araştırmaktır.
Yöntem: Çalışmada Sprague-Dawley sıçanlar (24 aylık) dört gruba ayrıldı: kontrol, aralıklı oruç, probiyotik ve bu tedavilerin kombinasyonu. Oksidatif stres belirteçleri olarak malondialdehit (MDA), ileri oksidasyon protein ürünleri (AOPP) ve miyeloperoksidaz (MPO) aktivitesi ölçüldü. Akciğer dokularındaki moleküler değişiklikleri tespit etmek için Zayıflatılmış Toplam Yansıma-Fourier Dönüşümlü Kızılötesi (ATR-FTIR) spektroskopisi kullanıldı.
Bulgular: Bulgularımız, hem aralıklı oruç tutmanın hem de probiyotiklerin, tek başına ve kombinasyon halinde, kontrol grubuna kıyasla MDA, AOPP ve MPO seviyelerini önemli ölçüde azalttığını, dolayısıyla oksidatif stresin azaldığını gösterdi. Spektral analizler, lipid bileşimi, protein konformasyonu ve oksidasyonu, ayrıca nükleik asitlerin fosfodiester gruplarındaki moleküler değişiklikleri ortaya koydu. LDA analizleri ile 1300-800 cm-1 bölgesinde en yüksek sınıflandırma doğruluğu (%93.18) elde edildi.
Sonuç: Aralıklı oruç ve probiyotikler, akciğerlerdeki yaşa bağlı oksidatif hasarı hafifletebilir ve yaşlanan bireylerde akciğer sağlığının korumasında umut vadeden terapötik bir potansiyel sunabilir.

Keywords

Yaşlanma, aralıklı oruç, FTIR spektroskopisi, akciğer, oksidatif stres

Ethical Statement

The study was approved by the Ethics Committee of the Saki Yenilli Experimental Animal Production and Practice Laboratory (approval number: 2022/03)

Supporting Institution

No funding was used for the study.

Protective Effects of Intermittent Fasting and Probiotics Usage on Oxidative Stress and Molecular Alterations in Aging Lung

Abstract

Objective: Aging is associated with increased oxidative stress and diminished cellular repair mechanisms, particularly in the lungs. This study investigates the protective effects of intermittent fasting (IF), SCD Probiotics, and their combination on oxidative stress and molecular alterations in the lungs of aging rats.
Materials and Methods: Sprague-Dawley rats (24 months old) were divided into four groups: control, intermittent fasting, probiotics, and a combination of both treatments. Oxidative stress markers, including malondialdehyde (MDA), advanced oxidation protein products (AOPP), and myeloperoxidase (MPO) activity, were measured. Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) spectroscopy was employed to detect molecular changes in lung tissues.
Results: Our findings demonstrated that both intermittent fasting and probiotics, individually and combined, significantly reduced MDA, AOPP, and MPO levels compared to the control group, indicating reduced oxidative stress. Spectral analysis indicated marked alterations in the profiles of lipid, protein, and nucleic acid, with machine learning methods identifying distinct bimolecular patterns in the treated groups.
Conclusion: Intermittent fasting and probiotics may ameliorate age-related oxidative damage in the lungs and offer promising therapeutic potential for maintaining lung health in aging populations.

Keywords

Aging, intermittent fasting, FTIR spectroscopy, lung, oxidative stress, probiotics

Ethical Statement

The study was approved by the Ethics Committee of the Saki Yenilli Experimental Animal Production and Practice Laboratory (approval number: 2022/03)

References

• 1. Schneider JL, Rowe JH, Garcia-de-Alba C, Kim CF, Sharpe AH, Haigis MC. The aging lung: Physiology, disease, and immunity. Cell 2021; 184: 1990–2019.
• 2. Cho SJ, Stout-Delgado HW. Aging and Lung Disease. Annu Rev Physiol 2020; 82: 433–459.
• 3. Liguori I, Russo G, Curcio F, Bulli G, Aran L, Della-Morte D, et al. Oxidative stress, aging, and diseases. Clin Interv Aging 2018; 13: 757–772.
• 4. Son TG, Zou Y, Yu BP, Lee J, Chung HY. Aging effect on myeloperoxidase in rat kidney and its modulation by calorie restriction. Free Radic Res 2005; 39: 283–289.
• 5. Chaudhary MR, Chaudhary S, Sharma Y, Singh TA, Mishra AK, Sharma S, et al. Aging, oxidative stress and degenerative diseases: mechanisms, complications and emerging therapeutic strategies. Biogerontology 2023; 24: 609–662.
• 6. Kehm R, Baldensperger T, Raupbach J, Höhn A. Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases. Redox Biol 2021; 42: 101901.
• 7. Aguilar Diaz De Leon J, Borges CR. Evaluation of Oxidative Stress in Biological Samples Using the Thiobarbituric Acid Reactive Substances Assay. J Vis Exp 2020; doi:10.3791/61122.
• 8. Zou Y-F, JiZe X-P, Li C-Y, Zhang C-W, Fu Y-P, Yin Z-Q, et al. Polysaccharide from aerial part of Chuanminshen violaceum alleviates oxidative stress and inflammatory response in aging mice through modulating intestinal microbiota. Front Immunol 2023; 14: 1159291.
• 9. Golbidi S, Daiber A, Korac B, Li H, Essop MF, Laher I. Health Benefits of Fasting and Caloric Restriction. Curr Diab Rep 2017; 17. doi:10.1007/s11892-017-0951-7.
• 10. Teker HT, Ceylani T. Intermittent fasting supports the balance of the gut microbiota composition. Int Microbiol 2022; doi: 10.1007/s10123-022-00272-7.
• 11. Mattson MP, Longo VD, Harvie M. Impact of intermittent fasting on health and disease processes. Ageing Res Rev 2017; 39: 46–58.
• 12. Wan MLY, Ling KH, El-Nezami H, Wang MF. Influence of functional food components on gut health. Crit Rev Food Sci Nutr 2019; 59: 1927–1936.
• 13. Bosco N, Noti M. The aging gut microbiome and its impact on host immunity. Genes Immun 2021; 22: 289–303.
• 14. Sivamaruthi BS, Fern LA, Rashidah Pg Hj Ismail DSN, Chaiyasut C. The influence of probiotics on bile acids in diseases and aging. Biomed Pharmacother 2020; 128: 110310.
• 15. Zhou A, Lei Y, Tang L, et al. Gut Microbiota: the Emerging Link to Lung Homeostasis and Disease. J Bacteriol. 2021;203(4):e00454-20. doi:10.1128/JB.00454-20.
• 16. Alswat AS. The Influence of the Gut Microbiota on Host Health: A Focus on the Gut-Lung Axis and Therapeutic Approaches. Life (Basel). 2024;14(10):1279. doi:10.3390/life14101279
• 17. Ceylani T. Effect of SCD probiotics supplemented with tauroursodeoxycholic acid (TUDCA) application on the aged rat gut microbiota composition. J Appl Microbiol. 2023 May 2;134(5):lxad092. doi: 10.1093/jambio/lxad092.
• 18. Teker HT, Ceylani T, Keskin S, Samgane G, Allahverdi H, Acikgoz E, et al. Supplementing probiotics during intermittent fasting proves more effective in restoring ileum and colon tissues in aged rats. J Cell Mol Med 2024; 28: 1–13.
• 19. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248–254.
• 20. Witko-Sarsat V, Friedlander M, Capeillère-Blandin C, et al. Advanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int 1996; 49: 1304–1313.
• 21. Bradley PP, Priebat DA, Christensen RD, et al. Measurement of cutaneous inflammation: estimation of neutrophil content with an enzyme marker. J Invest Dermatol 1982; 78: 206–209.
• 22. Ceylani T, Teker HT, Samgane G, Gurbanov R, Intermittent fasting-induced biomolecular modifications in rat tissues detected by ATR-FTIR spectroscopy and machine learning algorithms. Anal Biochem 2022; 654, 114825.
• 23. Yonar D, Severcan M, Gurbanov R, Sandal A, Yilmaz U, Emri S, Severcan F, Rapid diagnosis of malignant pleural mesothelioma and its discrimination from lung cancer and benign exudative effusions using blood serum. Biochim Biophys Acta Mol Basis Dis 2022; 1868(10), 166473.
• 24. Stockman MC, Thomas D, Burke J, Apovian CM. Intermittent Fasting: Is the Wait Worth the Weight? Curr Obes Rep 2018; 7: 172–185.
• 25. Hajam YA, Rani R, Ganie SY, Sheikh TA, Javaid D, Qadri SS, et al. Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives. Cells 2022; 11. doi:10.3390/cells11030552.
• 26. Luceri C, Bigagli E, Femia AP, Caderni G, Giovannelli L, Lodovici M. Aging related changes in circulating reactive oxygen species (ROS) and protein carbonyls are indicative of liver oxidative injury. Toxicol reports 2018; 5: 141–145.
• 27. Aydin S, Atukeren P, Cakatay U, Uzun H, Altuğ T. Gender-dependent oxidative variations in liver of aged rats. Biogerontology 2010; 11: 335–346.
• 28. Kumar D, Rizvi SI. A critical period in lifespan of male rats coincides with increased oxidative stress. Arch Gerontol Geriatr 2014; 58: 427–433.
• 29. Tripathi SS, Kumar R, Arya JK, Rizvi SI. Plasma from Young Rats Injected into Old Rats Induce Antiaging Effects. Rejuvenation Res 2021; 24: 206–212.
• 30. Uzun D, Korkmaz GG, Sitar ME, Cebe T, Yanar K, Cakatay U, et al. Oxidative damage parameters in renal tissues of aged and young rats based on gender. Clin Interv Aging 2013; 8: 809–815.
• 31. Bhoumik S, Kumar R, Rizvi SI. Time restricted feeding provides a viable alternative to alternate day fasting when evaluated in terms of redox homeostasis in rats. Arch Gerontol Geriatr. 2020; 91: 104188. doi:10.1016/j.archger.2020.104188.
• 32. Descamps O, Riondel J, Ducros V, Roussel AM. Mitochondrial production of reactive oxygen species and incidence of age-associated lymphoma in OF1 mice: effect of alternate-day fasting. Mech Ageing Dev. 2005; 126(11): 1185-1191. doi:10.1016/j.mad.2005.06.007.
• 33. Sánchez Macarro M, Ávila-Gandía V, Pérez-Piñero S, Cánovas F, García-Muñoz AM, Abellán-Ruiz MS, et al. Antioxidant Effect of a Probiotic Product on a Model of Oxidative Stress Induced by High-Intensity and Duration Physical Exercise. Antioxidants (Basel) 2021; 10. doi:10.3390/antiox10020323.
• 34. Liu R, Sun B. Lactic Acid Bacteria and Aging: Unraveling the Interplay for Healthy Longevity. Aging Dis 2023; 15: 1487–1498.
• 35. Li W, Gao L, Huang W, Ma Y, Muhammad I, Hanif A, et al. Antioxidant properties of lactic acid bacteria isolated from traditional fermented yak milk and their probiotic effects on the oxidative senescence of Caenorhabditis elegans. Food Funct 2022; 13: 3690–3703.
• 36. Nakagawa H, Miyazaki T. Beneficial effects of antioxidative lactic acid bacteria. AIMS Microbiol 2017; 3: 1–7.
• 37. Michalickova D, Kotur-Stevuljevic J, Miljkovic M, Dikic N, Kostic-Vucicevic M, Andjelkovic M, et al. Effects of Probiotic Supplementation on Selected Parameters of Blood Prooxidant-Antioxidant Balance in Elite Athletes: A Double-Blind Randomized Placebo-Controlled Study. J Hum Kinet 2018; 64: 111–122.
• 38. Hays KE, Pfaffinger JM, Ryznar R. The interplay between gut microbiota, short-chain fatty acids, and implications for host health and disease. Gut Microbes. 2024; 16(1): 2393270. doi:10.1080/19490976.2024.2393270.
• 39. Gonos ES, Kapetanou M, Sereikaite J, Bartosz G, Naparło K, Grzesik M, et al. Origin and pathophysiology of protein carbonylation, nitration and chlorination in age-related brain diseases and aging. Aging (Albany NY) 2018; 10: 868–901.
• 40. Vileno B, Jeney S, Sienkiewicz A, Marcoux PR, Miller LM, Forró L. Evidence of lipid peroxidation and protein phosphorylation in cells upon oxidative stress photo-generated by fullerols. Biophys Chem. 2010; 152(1-3): 164-169. doi:10.1016/j.bpc.2010.09.004.
• 41. Schindowski K, Leutner S, Kressmann S, Eckert A, Müller WE. Age-related increase of oxidative stress-induced apoptosis in mice prevention by Ginkgo biloba extract (EGb761). J Neural Transm (Vienna). 2001; 108(8-9): 969-978. doi:10.1007/s007020170016.
• 42. Matera MG, Calzetta L, Cazzola M. Oxidation pathway and exacerbations in COPD: the role of NAC. Expert Rev Respir Med 2016; 10: 89–97.
• 43. Huetsch JC, Suresh K, Shimoda LA. Regulation of Smooth Muscle Cell Proliferation by NADPH Oxidases in Pulmonary Hypertension. Antioxidants (Basel) 2019; 8. doi:10.3390/antiox8030056.
• 44. Fulton DJR, Li X, Bordan Z, Haigh S, Bentley A, Chen F, et al. Reactive Oxygen and Nitrogen Species in the Development of Pulmonary Hypertension. Antioxidants (Basel) 2017; 6. doi:10.3390/antiox6030054.
• 45. Otoupalova E, Smith S, Cheng G, Thannickal VJ. Oxidative Stress in Pulmonary Fibrosis. Compr Physiol 2020; 10: 509–547.
• 46. Teker HT, Ceylani T, Keskin S, Samgane G, Baba B, Acıkgoz E, et al. Reduced liver damage and fibrosis with combined SCD Probiotics and intermittent fasting in aged rat. J Cell Mol Med 2023; 1–11.