Hexagonal Boron Nitride Nanoparticles Prevent Neurodegeneration in Septic Rat Brain

Öz

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.

Anahtar Kelimeler

• Apoptosis
• hexagonal boron nitride nanoparticles
• LPS
• neuroinflammation
• oxidative stress
• sepsis

Hekzagonal Boron Nitrür Nanopartikülleri Septik Sıçan Beyninde Nörodejenerasyonu Önler

Öz

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.

Anahtar Kelimeler

• Apoptozis
• hekzagonal boron nitrür nanopartikülleri
• LPS
• nöroinflamasyon
• oksidatif stres
• sepsis

Kaynakça

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