Abstract
Sepsis, which develops with the triggering of an uncontrolled inflammatory response, causes multiple organ damage and dysfunction. Neuroinflammation occurring in sepsis causes varying degrees of deterioration in the central nervous system. Hexagonal boron nitride (h-BN) nanoparticles composed of boron and nitrogen have potential biomedical applications and are well tolerated by animals. Research has indicated that h-BN nanoparticles exhibit antioxidative characteristics. Although the anti-inflammatory properties of the boron present in them, the effectiveness of h-BN nanoparticles on systemic inflammation or neuroinflammation is unknown. Thus, the aim of this research was to investigate the potential protective benefits of h-BN nanoparticles against inflammation induced by lipopolysaccharide (LPS) in rat brains. An intraperitoneal 5 mg/kg dose of LPS was used to induce sepsis in Sprague Dawley rats. h-BN nanoparticles were given at 50 μg/kg and 100 μg/kg concentrations 24 h before LPS injection. To assess the prophylactic effect of h-BN nanoparticles in sepsis-induced neurodegeneration, besides measuring pro-inflammatory, oxidative stress, and apoptosis markers in brain tissues, the cerebral cortex and hippocampus were also examined histopathologically. Our ELISA results show that h-BN nanoparticles inhibit inflammation in the brain as evidenced by the reduction in LPS-induced increase in tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels. h-BN nanoparticles diminished the oxidative stress index and lowered cytochrome c and caspase-3 levels, components of the intrinsic apoptotic pathway. Our histopathological analyzes demonstrated that neuronal and neuroglial damage in the cerebral cortex and hippocampus was also prevented by the treatment of h-BN nanoparticles. These results implicated that h-BN nanoparticles could have a neuroprotective effect against sepsis-induced neurodegeneration through their anti-inflammatory, antioxidant, and anti-apoptotic properties.
Keywords
Apoptosis hexagonal boron nitride nanoparticles LPS neuroinflammation oxidative stress sepsis
References
- 1. Meneses G, Cárdenas G, Espinosa A, Rassy D, Pérez‐Osorio IN, Bárcena B, et al. Sepsis: developing new alternatives to reduce neuroinflammation and attenuate brain injury. Ann N Y Acad Sci. 2019;1437(1):43-56.
- 2. Danielski LG, Giustina AD, Badawy M, Barichello T, Quevedo J, Dal-Pizzol F, et al. Brain barrier breakdown as a cause and consequence of neuroinflammation in sepsis. Mol Neurobiol. 2018;55:1045-1053.
- 3. Batista CRA, Gomes GF, Candelario-Jalil E, Fiebich BL, De Oliveira ACP. Lipopolysaccharide-induced neuroinflammation as a bridge to understand neurodegeneration. Int J Mol Sci. 2019;20(9):2293.
- 4. Shabab T, Khanabdali R, Moghadamtousi SZ, Kadir HA, Mohan G. Neuroinflammation pathways: a general review. Int J Neurosci. 2017;127(7): 624-633.
- 5. Nielsen FH, Meacham SL. Growing evidence for human health benefits of boron. J Evid Based Complementary Altern Med. 2011;16(3):169-180.
- 6. Hunt CD, Idso JP. Dietary boron as a physiological regulator of the normal inflammatory response: a review and current research progress. J Trace Elem Exp Med. 1999;12(3):221-233.
- 7. Romero-Aguilar KS, Arciniega-Martínez IM, Farfán-García ED, Campos-Rodríguez R, Reséndiz-Albor AA, Soriano-Ursúa MA. Effects of boron-containing compounds on immune responses: review and patenting trends. Expert Opin Ther Pat. 2019;29(5):339-351.
- 8. Weng Q, Wang X, Wang X, Bando Y, Golberg D. Functionalized hexagonal boron nitride nanomaterials: emerging properties and applications. Chem Soc Rev. 2016;45(14):3989-4012.
- 9. Roy S, Zhang X, Puthirath AB, Meiyazhagan A, Bhattacharyya S, Rahman MM. et al. Structure, properties and applications of two‐dimensional hexagonal boron nitride. Adv Mater. 2021;33(44):2101589.
- 10. Merlo A, Mokkapati VRSS, Pandit S, Mijakovic I. Boron nitride nanomaterials: biocompatibility and bio-applications. Biomater Sci. 2018;6(9):2298-2311.
- 11. Kar F, Hacıoğlu C, Göncü Y, Söğüt İ, Şenturk H, Burukoğlu Dönmez D. et al. In vivo assessment of the effect of hexagonal boron nitride nanoparticles on biochemical, histopathological, oxidant and antioxidant status. J Clust Sci. 2021;32:517-529.
- 12. Aydin N, Turkez H, Tozlu OO, Arslan ME, Yavuz M, Sonmez E. et al. Ameliorative Effects by Hexagonal Boron Nitride Nanoparticles against Beta Amyloid Induced Neurotoxicity. Nanomaterials. 2022;12(15):2690.
- 13. Küçükdoğru R, Türkez H, Arslan ME, Tozlu ÖÖ, Sönmez E, Mardinoğlu A. et al. Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson’s disease model against MPP+ induced apoptosis. Metab Brain Dis. 2020;35:947-957.
- 14. Taskin IC, Sen O, Emanet M, Culha M, Yilmaz B. Hexagonal boron nitrides reduce the oxidative stress on cells. Nanotechnology. 2020;31(21):215101.
- 15. Xu K, Li H, Zhang B, Le M, Huang Q, Fu R. et al. Integrated transcriptomics and metabolomics analysis of the hippocampus reveals altered neuroinflammation, downregulated metabolism and synapse in sepsis-associated encephalopathy. Front Pharmacol, 2022;13:1004745.
- 16. Piva SA, McCreadie V, Latronico N. Neuroinflammation in sepsis: sepsis associated delirium. Cardiovasc Hematol Disord Drug Targets. 2015;15(1):10-18.
- 17. Lopes PC. LPS and neuroinflammation: a matter of timing. Inflammopharmacology. 2016;24:291-293.
- 18. Naghii MR, Mofid M, Asgari AR, Hedayati M, Daneshpour MS. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. J Trace Elem Med Biol. 2011;25(1):54-58.
- 19. Turkez H, Arslan ME, Tatar A. Mardinoglu A. Promising potential of boron compounds against Glioblastoma: In Vitro antioxidant, anti-inflammatory and anticancer studies. Neurochem Int. 2021;149:105137.
- 20. Ince S, Kucukkurt I, Demirel HH, Arslan-Acaroz D, Varol N. Boron, a trace mineral, alleviates gentamicin-induced nephrotoxicity in rats. Biol Trace Elem Res. 2020;195(2):515-524.
- 21. Kucukkurt I, Ince S, Eryavuz A, Demirel HH, Arslan‐Acaroz D, Zemheri‐Navruz F, Durmus I. The effects of boron‐supplemented diets on adipogenesis‐related gene expressions, anti‐inflammatory, and antioxidative response in high‐fat fed rats. J Biochem Mol Toxicol. 2023;37(2):e23257.
- 22. Biswas SK. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox?. Oxid Med Cell Longev. 2016;2016.
- 23. Barichello T, Machado RA, Constantino L, Valvassori SS, Réus G, Martins MR. Antioxidant treatment prevented late memory impairment in an animal model of sepsis. Crit Care Med. 2007;35(9):2186-2190.
- 24. Chandra J, Samali A, Orrenius S. Triggering and modulation of apoptosis by oxidative stress. Free Radic Biol Med. 2000;29(3-4):323-333.
- 25. Harjai M, Bogra J, Kohli M, Pant AB. Is suppression of apoptosis a new therapeutic target in sepsis?. Anaesth Intensive Care. 2013;41(2):175-183.
- 26. Acaroz U, Ince S, Arslan-Acaroz D, Gurler Z, Kucukkurt I, Demirel HH. et al. The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats. Food Chem Toxicol. 2018;118:745-752.
- 27. Ataizi ZS, Ozkoc M, Kanbak G, Karimkhani H, Donmez DB, Ustunisik N, Ozturk B. Evaluation of the neuroprotective role of boric acid in preventing traumatic brain injury-mediated oxidative stress. Turk Neurosurg. 2021;31(4):25692-18.
- 28. Ozdemir HS, Yunusoglu O, Sagmanligil V, Yasar S, Colcimen N, Goceroglu R, Catalkaya E. Investigation of the pharmacological, behavioral, and biochemical effects of boron in parkinson-indicated rats. Cell Mol Biol. 2022;68(8):13-21.
- 29. Turkez H, Yıldırım S, Sahin E, Arslan ME, Emsen B, Tozlu OO, Mardinoglu A. Boron Compounds Exhibit Protective Effects against Aluminum-Induced Neurotoxicity and Genotoxicity: In Vitro and In Vivo Study. Toxics. 2022;10(8):428.
Abstract
Kontrolsüz bir inflamatuar yanıtın tetiklenmesi ile gelişen sepsis, çoklu organ hasarına ve disfonksiyona neden olmaktadır. Sepsiste meydana gelen nöroinflamasyon, merkezi sinir sisteminde değişen derecelerde bozulmalara yol açmaktadır. Bor ve nitrojenden oluşan hekzagonal bor nitrür (h-BN) nanopartikülleri potansiyel biyomedikal uygulamalara sahiptir ve hayvanlar tarafından iyi tolare edilmektedir. Çalışmalar h-BN nanopartiküllerinin antioksidatif özelliklerine sahip olduğunu bildirmiştir. İçerdiği boronun anti-inflamatuar özellikleri bilinmesine rağmen h-BN nanopartiküllerinin sistemik inflamasyon veya nöroinflamasyon üzerindeki etkinliği bilinmemektedir. Bu nedenle, bu çalışmada h-BN nanopartiküllerinin sıçan beyninde lipopolisakkarid (LPS) kaynaklı inflamasyon üzerindeki koruyucu etkilerini araştırmak amaçlanmıştır. Sprague Dawley sıçanlarında sepsis oluşturmak için 5 mg/kg dozda LPS intraperitoneal olarak uygulanmıştır. h-BN nanopartikülleri, LPS enjeksiyonundan 24 saat önce 50 μg/kg ve 100 μg/kg konsantrasyonlarda verilmiştir. h-BN nanopartiküllerinin sepsis kaynaklı nörodejenerasyondaki profilaktik etkisini belirlemek için beyin dokularında pro-inflamatuar, oksidatif stres ve apoptoz belirteçlerinin ölçülmesinin yanı sıra serebral korteks ve hipokampüs histopatolojik olarak incelenmiştir. ELISA sonuçlarımız, h-BN nanopartiküllerinin, tümör nekrozis faktör-alfa (TNF-α) ve interlökin-1 beta (IL-1β) seviyelerinde LPS'nin neden olduğu artıştaki azalma ile kanıtlandığı gibi beyindeki inflamayonu önlediğini göstermektedir. h-BN nanopartikülleri ayrıca oksidatif stres indeksini düşürmüş ve intrinsik apoptotik yolak bileşenleri olan sitokrom c ve kaspaz-3 seviyelerini azaltmıştır. Histopatolojik analizlerimiz, serebral korteks ve hipokampüsteki nöronal ve nöroglial hasarın da h-BN nanopartiküllerinin uygulanması ile önlendiğini göstermiştir. Bu sonuçlar, h-BN nanopartiküllerinin anti-inflamatuar, antioksidan ve anti-apoptotik özellikleri sayesinde sepsis kaynaklı nörodejenasyona karşı koruyucu bir etkiye sahip olabileceğine işaret etmektedir.
Keywords
Apoptozis hekzagonal boron nitrür nanopartikülleri LPS nöroinflamasyon oksidatif stres sepsis
References
- 1. Meneses G, Cárdenas G, Espinosa A, Rassy D, Pérez‐Osorio IN, Bárcena B, et al. Sepsis: developing new alternatives to reduce neuroinflammation and attenuate brain injury. Ann N Y Acad Sci. 2019;1437(1):43-56.
- 2. Danielski LG, Giustina AD, Badawy M, Barichello T, Quevedo J, Dal-Pizzol F, et al. Brain barrier breakdown as a cause and consequence of neuroinflammation in sepsis. Mol Neurobiol. 2018;55:1045-1053.
- 3. Batista CRA, Gomes GF, Candelario-Jalil E, Fiebich BL, De Oliveira ACP. Lipopolysaccharide-induced neuroinflammation as a bridge to understand neurodegeneration. Int J Mol Sci. 2019;20(9):2293.
- 4. Shabab T, Khanabdali R, Moghadamtousi SZ, Kadir HA, Mohan G. Neuroinflammation pathways: a general review. Int J Neurosci. 2017;127(7): 624-633.
- 5. Nielsen FH, Meacham SL. Growing evidence for human health benefits of boron. J Evid Based Complementary Altern Med. 2011;16(3):169-180.
- 6. Hunt CD, Idso JP. Dietary boron as a physiological regulator of the normal inflammatory response: a review and current research progress. J Trace Elem Exp Med. 1999;12(3):221-233.
- 7. Romero-Aguilar KS, Arciniega-Martínez IM, Farfán-García ED, Campos-Rodríguez R, Reséndiz-Albor AA, Soriano-Ursúa MA. Effects of boron-containing compounds on immune responses: review and patenting trends. Expert Opin Ther Pat. 2019;29(5):339-351.
- 8. Weng Q, Wang X, Wang X, Bando Y, Golberg D. Functionalized hexagonal boron nitride nanomaterials: emerging properties and applications. Chem Soc Rev. 2016;45(14):3989-4012.
- 9. Roy S, Zhang X, Puthirath AB, Meiyazhagan A, Bhattacharyya S, Rahman MM. et al. Structure, properties and applications of two‐dimensional hexagonal boron nitride. Adv Mater. 2021;33(44):2101589.
- 10. Merlo A, Mokkapati VRSS, Pandit S, Mijakovic I. Boron nitride nanomaterials: biocompatibility and bio-applications. Biomater Sci. 2018;6(9):2298-2311.
- 11. Kar F, Hacıoğlu C, Göncü Y, Söğüt İ, Şenturk H, Burukoğlu Dönmez D. et al. In vivo assessment of the effect of hexagonal boron nitride nanoparticles on biochemical, histopathological, oxidant and antioxidant status. J Clust Sci. 2021;32:517-529.
- 12. Aydin N, Turkez H, Tozlu OO, Arslan ME, Yavuz M, Sonmez E. et al. Ameliorative Effects by Hexagonal Boron Nitride Nanoparticles against Beta Amyloid Induced Neurotoxicity. Nanomaterials. 2022;12(15):2690.
- 13. Küçükdoğru R, Türkez H, Arslan ME, Tozlu ÖÖ, Sönmez E, Mardinoğlu A. et al. Neuroprotective effects of boron nitride nanoparticles in the experimental Parkinson’s disease model against MPP+ induced apoptosis. Metab Brain Dis. 2020;35:947-957.
- 14. Taskin IC, Sen O, Emanet M, Culha M, Yilmaz B. Hexagonal boron nitrides reduce the oxidative stress on cells. Nanotechnology. 2020;31(21):215101.
- 15. Xu K, Li H, Zhang B, Le M, Huang Q, Fu R. et al. Integrated transcriptomics and metabolomics analysis of the hippocampus reveals altered neuroinflammation, downregulated metabolism and synapse in sepsis-associated encephalopathy. Front Pharmacol, 2022;13:1004745.
- 16. Piva SA, McCreadie V, Latronico N. Neuroinflammation in sepsis: sepsis associated delirium. Cardiovasc Hematol Disord Drug Targets. 2015;15(1):10-18.
- 17. Lopes PC. LPS and neuroinflammation: a matter of timing. Inflammopharmacology. 2016;24:291-293.
- 18. Naghii MR, Mofid M, Asgari AR, Hedayati M, Daneshpour MS. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. J Trace Elem Med Biol. 2011;25(1):54-58.
- 19. Turkez H, Arslan ME, Tatar A. Mardinoglu A. Promising potential of boron compounds against Glioblastoma: In Vitro antioxidant, anti-inflammatory and anticancer studies. Neurochem Int. 2021;149:105137.
- 20. Ince S, Kucukkurt I, Demirel HH, Arslan-Acaroz D, Varol N. Boron, a trace mineral, alleviates gentamicin-induced nephrotoxicity in rats. Biol Trace Elem Res. 2020;195(2):515-524.
- 21. Kucukkurt I, Ince S, Eryavuz A, Demirel HH, Arslan‐Acaroz D, Zemheri‐Navruz F, Durmus I. The effects of boron‐supplemented diets on adipogenesis‐related gene expressions, anti‐inflammatory, and antioxidative response in high‐fat fed rats. J Biochem Mol Toxicol. 2023;37(2):e23257.
- 22. Biswas SK. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox?. Oxid Med Cell Longev. 2016;2016.
- 23. Barichello T, Machado RA, Constantino L, Valvassori SS, Réus G, Martins MR. Antioxidant treatment prevented late memory impairment in an animal model of sepsis. Crit Care Med. 2007;35(9):2186-2190.
- 24. Chandra J, Samali A, Orrenius S. Triggering and modulation of apoptosis by oxidative stress. Free Radic Biol Med. 2000;29(3-4):323-333.
- 25. Harjai M, Bogra J, Kohli M, Pant AB. Is suppression of apoptosis a new therapeutic target in sepsis?. Anaesth Intensive Care. 2013;41(2):175-183.
- 26. Acaroz U, Ince S, Arslan-Acaroz D, Gurler Z, Kucukkurt I, Demirel HH. et al. The ameliorative effects of boron against acrylamide-induced oxidative stress, inflammatory response, and metabolic changes in rats. Food Chem Toxicol. 2018;118:745-752.
- 27. Ataizi ZS, Ozkoc M, Kanbak G, Karimkhani H, Donmez DB, Ustunisik N, Ozturk B. Evaluation of the neuroprotective role of boric acid in preventing traumatic brain injury-mediated oxidative stress. Turk Neurosurg. 2021;31(4):25692-18.
- 28. Ozdemir HS, Yunusoglu O, Sagmanligil V, Yasar S, Colcimen N, Goceroglu R, Catalkaya E. Investigation of the pharmacological, behavioral, and biochemical effects of boron in parkinson-indicated rats. Cell Mol Biol. 2022;68(8):13-21.
- 29. Turkez H, Yıldırım S, Sahin E, Arslan ME, Emsen B, Tozlu OO, Mardinoglu A. Boron Compounds Exhibit Protective Effects against Aluminum-Induced Neurotoxicity and Genotoxicity: In Vitro and In Vivo Study. Toxics. 2022;10(8):428.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | ORİJİNAL MAKALE |
| Authors | |
| Publication Date | September 27, 2023 |
| Published in Issue | Year 2023 Volume: 45 Issue: 5 |