Hipokampus ve Serumda NO, H2S ve CO'nun Tiyol/Disülfit Dengesi ve İleri Oksidasyon Protein Ürünleri Üzerindeki Etkileri

Giriş: Nitrik oksit (NO), hidrojen sülfür (H2S) ve karbon monoksit (CO) gaz otokoidler olarak bilinir. Eksojen NO, H2S ve CO uygulamasının hipokampus ve serumda tiyol/disülfit dengesini ve ileri oksidasyon protein ürünlerini (AOPP'ler) nasıl değiştirdiği açık değildir. Gereç ve Yöntem: Çalışmada, sıçanlara NO donörü olarak L-arginin (100 mg/kg), H2S donörü olarak NaHS (10 mg/kg) ve CO donörü olarak CORM-2 (10 mg/kg) ( trikarbonildiklororutenyum dimer) enjekte edildi. Hipokampus ve serum örneklerinde tiyol/disülfit dengesi ve ileri protein oksidasyon ürünleri (AOPPs) analiz edildi. Bulgular: L-arginin grubunun hipokampüsündeki serbest tiyol seviyesi, kontrol grubunun serbest tiyol seviyesine göre istatistiksel olarak azaldı (****p≤0.0001). L-arginin grubunun hipokampüsündeki disülfid düzeyi kontrol grubuna göre istatistiksel olarak yüksek bulundu (***p=0,009). NaHS grubu ve CORM-2 grubunun hipokampal total tiyol düzeyi istatistiksel olarak artarken (sırasıyla ***p=0,008,*p=0,0157), CORM-2 grubunun serum disülfit düzeyi azaldı (***p=0,0005). NaHS grubunun serum ve hipokampus AOPP'leri kontrol grubuna göre istatistiksel olarak yüksekti (sırasıyla ***p=0,0006, **p=0,0047). Benzer şekilde CORM-2 grubunda hipokampal AOPPs düzeyi kontrol grubundaki AOPPs düzeyine göre istatistiksel olarak yüksek bulundu (*p=0,0437). Sonuç: NaHS, tiyol/disülfit dengesini iyileştirebilirken, CORM-2 ve L-Arginin için yeni çalışmalara ihtiyaç vardır. Bu çalışma, NO, H2S ve CO'nun hipokampus ve serumdaki tiyol/disülfit dengesi ve AOPPs'ler üzerindeki etkilerini bildiren ilk çalışmadır.
Anahtar Kelimeler:

NO, H2S, CO, AOPPs, Tiyol/Disülfit

Effects of NO, H2S and CO on Thiol/Disulfide Balance and Advanced Oxidation Protein Products in Hippocampus and Serum

Introduction: Nitric oxide (NO), hydrogen sulfide (H2S), and carbon monoxide (CO) are known as gaseous autocoids. It is not clear how the application of exogenous NO, H2S and CO alters the thiol/disulfide balance and advanced oxidation protein products (AOPPs) in the hippocampus and serum. Materials and Methods: In the study, rats were exogenously injected with L-arginine (100 mg/kg) as a NO donor, NaHS (10 mg/kg) as a H2S donor, and CORM-2 (10 mg/kg) as a CO donor (II) (a tricarbonyldichlororuthenium dimer). Thiol/disulfide balance and advanced protein oxidation products were analyzed in hippocampus and serum samples. Results: The native thiol level in the hippocampus of the L-arginine group was statistically decreased compared to the native thiol level of the control group (****p≤0.0001). The disulfide level in the hippocampus of the L-arginine group was statistically increased compared to the control group (***p=0.009). Hippocampal total thiol level of NaHS group and CORM-2 group increased statistically (***p=0.008,*p=0.0157, respectively), while serum disulfide level of CORM-2 group decreased (***p=0.0005). Serum and hippocampus AOPPs levels of the NaHS group were statistically increased compared to the control group (***p=0.0006, **p=0.0047, respectively). Similarly, the hippocampal AOPP level in the CORM-2 group was found to be statistically increased compared to the AOPP level in the control group (*p=0.0437). Conclusion: As NaHS can improve thiol/disulfide balance, new studies are needed for CORM-2 and L-Arginine. This study is the first to report the effects of NO, H2S and CO on thiol/disulfide balance and AOPPs in the hippocampus and serum.

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  • 1. K. Wang, Y. Wang, H. Zhang, X. Li, and W. Han, A Review of the Synthesis of Nitric Oxide Donor and Donor Derivatives with Pharmacological Activities, Mini Reviews in Medicinal Chemistry. 22 (2022) 873-883.
  • 2. A. Sahebnasagh, F. Saghafi, S. Negintaji, T. Hu, M. Shabani-Borujeni, M. Safdari, H. R. Ghaleno, L. Miao, Y. Qi, and M. Wang, Nitric oxide and immune responses in cancer: Searching for new therapeutic strategies, Current medicinal chemistry. 29 (2022) 1561-1595.
  • 3. X. Yang, W. Lu, M. Wang, C. Tan, and B. Wang, “CO in a pill”: Towards oral delivery of carbon monoxide for therapeutic applications, Journal of Controlled Release. 338 (2021) 593-609.
  • 4. D. O. Schairer, J. S. Chouake, J. D. Nosanchuk and A. J. Friedman, The potential of nitric oxide releasing therapies as antimicrobial agents, Virulence. 3 (2012) 271-279.
  • 5. C. Di Pietro, H. H. Öz, T. S. Murray and E. M. Bruscia, Targeting the heme oxygenase 1/carbon monoxide pathway to resolve lung hyper-inflammation and restore a regulated immune response in cystic fibrosis, Frontiers in Pharmacology. 11 (2020) 1059.
  • 6. K. R. Olson, Mitochondrial adaptations to utilize hydrogen sulfide for energy and signaling, Journal of Comparative Physiology B. 182 (2012) 881-897.
  • 7. G. R. Martin, G. W. McKnight, M. S. Dicay, C. S. Coffin, J. G. Ferraz, and J. L. Wallace, Hydrogen sulphide synthesis in the rat and mouse gastrointestinal tract, Digestive and Liver Disease. 42 (2010) 103-109.
  • 8. E. Blackstone and M. B. Roth, Suspended animation-like state protects mice from lethal hypoxia, Shock. 27 (2007) 370-372.
  • 9. R. Dugue and F. C. Barone, Ischemic, traumatic and neurodegenerative brain inflammatory changes, Future Neurology. 11 (2016) 77-96.
  • 10. V. Calabrese, C. Mancuso, M. Calvani, E. Rizzarelli, D. A. Butterfield, and A. M. Stella, Nitric oxide in the central nervous system: neuroprotection versus neurotoxicity, Nat Rev Neurosci. 8 (2007) 766-75.
  • 11. R. Scatena, P. Bottoni, A. Pontoglio and B. Giardina, Pharmacological modulation of nitric oxide release: new pharmacological perspectives, potential benefits and risks, Current medicinal chemistry. 17 (2010) 61-73.
  • 12. B. Wang, W. Cao, S. Biswal and S. Doré, Carbon monoxide–activated Nrf2 pathway leads to protection against permanent focal cerebral ischemia, Stroke. 42 (2011) 2605-2610.
  • 13. J. Ji, P. Xiang, T. Li, L. Lan, X. Xu, G. Lu, H. Ji, Y. Zhang, and Y. Li, NOSH-NBP, a novel nitric oxide and hydrogen sulfide-releasing hybrid, attenuates ischemic stroke-induced neuroinflammatory injury by modulating microglia polarization, Frontiers in cellular neuroscience. 11 (2017) 154.
  • 14. X. Cao, L. Cao, L. Ding and J.-s. Bian, A new hope for a devastating disease: hydrogen sulfide in Parkinson’s disease, Molecular Neurobiology. 55 (2018) 3789-3799.
  • 15. O. Erel and S. Neselioglu, A novel and automated assay for thiol/disulphide homeostasis, Clinical biochemistry. 47 (2014) 326-332.
  • 16. P. V. Oliveira and F. R. Laurindo, Implications of plasma thiol redox in disease, Clinical Science. 132 (2018) 1257-1280.
  • 17. A. K. Erenler and T. Yardan, Clinical Utility of Thiol/Disulfide Homeostasis, Clinical laboratory. 63 (2017) 867-870.
  • 18. Y. Zhao, L. Zhang, X. Ouyang, Z. Jiang, Z. Xie, L. Fan, D. Zhu, and L. Li, Advanced oxidation protein products play critical roles in liver diseases, European Journal of Clinical Investigation. 49 (2019) e13098.
  • 19. M. Cristani, A. Speciale, A. Saija, S. Gangemi, P. Lucia Minciullo, and F. Cimino, Circulating advanced oxidation protein products as oxidative stress biomarkers and progression mediators in pathological conditions related to inflammation and immune dysregulation, Current medicinal chemistry. 23 (2016) 3862-3882.
  • 20. V. Witko-Sarsat, M. Friedlander, T. N. Khoa, C. Capeillère-Blandin, A. T. Nguyen, S. Canteloup, J.-M. Dayer, P. Jungers, T. Drüeke, and B. Descamps-Latscha, Advanced oxidation protein products as novel mediators of inflammation and monocyte activation in chronic renal failure1, 2, The Journal of immunology. 161 (1998) 2524-2532.
  • 21. G. Conti, D. Caccamo, R. Siligato, G. Gembillo, E. Satta, D. Pazzano, N. Carucci, A. Carella, G. Del Campo, and A. Salvo, Association of higher advanced oxidation protein products (AOPPs) levels in patients with diabetic and hypertensive nephropathy, Medicina. 55 (2019) 675.
  • 22. S. O. Kayaalp, Rasyonel Tedavi Yönünden Tıbbi Farmakoloji. 13 ed. 2012, Ankara: Feryal matbaacılık San. Tic. Ltd. Şti. 1276-1280
  • 23. G. Ellman and H. Lysko, A precise method for the determination of whole blood and plasma sulfhydryl groups, Analytical biochemistry. 93 (1979) 98-102.
  • 24. M. Hanasand, R. Omdal, K. B. Norheim, L. G. Gøransson, C. Brede, and G. Jonsson, Improved detection of advanced oxidation protein products in plasma, Clinica chimica acta. 413 (2012) 901-906.
  • 25. I. M. Skoie, I. Dalen, R. Omdal and G. Jonsson, Malondialdehyde and advanced oxidation protein products are not increased in psoriasis: a controlled study, Archives of Dermatological Research. 311 (2019) 299-308.
  • 26. L.-L. Pan, M. Qin, X.-H. Liu and Y.-Z. Zhu, The role of hydrogen sulfide on cardiovascular homeostasis: an overview with update on immunomodulation, Frontiers in pharmacology. 8 (2017) 686.
  • 27. F. K. Al-thoubaity, Molecular classification of breast cancer: A retrospective cohort study, Annals of Medicine and Surgery. 49 (2020) 44-48.
  • 28. H. Dai, D. N. Coleman, L. Hu, I. Martinez-Cortés, M. Wang, C. Parys, X. Shen, and J. J. Loor, Methionine and arginine supplementation alter inflammatory and oxidative stress responses during lipopolysaccharide challenge in bovine mammary epithelial cells in vitro, J Dairy Sci. 103 (2020) 676-689.
  • 29. Y. Qiu, X. Yang, L. Wang, K. Gao, and Z. Jiang, L-Arginine Inhibited Inflammatory Response and Oxidative Stress Induced by Lipopolysaccharide via Arginase-1 Signaling in IPEC-J2 Cells, Int J Mol Sci. 20 (2019)
  • 30. F. Scalera, E. I. Closs, E. Flick, J. Martens-Lobenhoffer, J. P. Boissel, U. Lendeckel, A. Heimburg, and S. M. Bode-Böger, Paradoxical effect of l-arginine: Acceleration of endothelial cell senescence, Biochemical and Biophysical Research Communications. 386 (2009) 650-655.
  • 31. H. Li, C. J. Meininger, J. James R. Hawker, T. E. Haynes, D. Kepka-Lenhart, S. K. Mistry, J. Sidney M. Morris, and G. Wu, Regulatory role of arginase I and II in nitric oxide, polyamine, and proline syntheses in endothelial cells, American Journal of Physiology-Endocrinology and Metabolism. 280 (2001) E75-E82.
  • 32. C. D. S. Barros, J. B. Livramento, M. G. Mouro, E. M. S. Higa, C. T. Moraes, and C. H. Tengan, L-Arginine Reduces Nitro-Oxidative Stress in Cultured Cells with Mitochondrial Deficiency, Nutrients. 13 (2021) 534.
  • 33. A. Federico, F. Morgillo, C. Tuccillo, F. Ciardiello, and C. Loguercio, Chronic inflammation and oxidative stress in human carcinogenesis, International journal of cancer. 121 (2007) 2381-2386.
  • 34. R. Siracusa, V. A. Voltarelli, A. T. Salinaro, S. Modafferi, S. Cuzzocrea, E. J. Calabrese, R. Di Paola, L. E. Otterbein, and V. Calabrese, NO, CO and H2S: A trinacrium of bioactive gases in the brain, Biochemical Pharmacology. 202 (2022) 115122.
  • 35. Y. Kimura and H. Kimura, Hydrogen sulfide protects neurons from oxidative stress, The FASEB Journal. 18 (2004) 1165-1167.
  • 36. Hydrogen Sulfide Increases Glutathione Production and Suppresses Oxidative Stress in Mitochondria, Antioxidants & Redox Signaling. 12 (2010) 1-13. 37. A. Tuzcu, R. A. Baykara, M. Alışık, A. Omma, G. K. Acet, E. Dogan, M. C. Cure, F. Duygun, E. Cure, and O. Erel, Alteration of Thiol-Disulfide Homeostasis in Fibromyalgia Syndrome, Acta Medica (Hradec Kralove). 62 (2019) 12-18.