Sodyum Pentaborat, Antioksidan, Anti-inflamatuar ve Anti-apoptotik Mekanizmalar Yoluyla Parasetamol Kaynaklı Dalak Toksisitesini Azaltır

Abstract

Paracetamol yaygın olarak kullanılan bir analjezik ve antipiretik ilaçtır, ancak aşırı dozu ciddi organ hasarına yol açabilir. PCM kaynaklı toksisitenin daha az araştırılmış hedeflerinden biri, kritik bir bağışıklık organı olan dalaktır. Bilinen biyolojik faydaları olan bir eser element olan bor, eski çağlardan beri terapötik olarak kullanılmaktadır. Bu çalışma, sodyum pentaborat (50 mg/kg ve 100 mg/kg, oral) olarak uygulanan borun sıçanlarda parasetamol kaynaklı dalak hasarına karşı koruyucu etkilerini değerlendirmek için tasarlanmıştır. Erkek Sprague-Dawley sıçanlarına altı gün boyunca sodyum pentaborat ile ön tedavi uygulandı, ardından tek bir toksik doz parasetamol (1 g/kg) uygulandı. PCM maruziyeti, malondialdehit (MDA), tümör nekroz faktörü-alfa (TNF-α), interlökin-1 beta (IL-1β) ve kaspaz-3'ün yüksek seviyeleriyle kanıtlandığı gibi, dalak dokusunda artan oksidatif strese ve inflamasyona yol açtı. Ek olarak, anahtar antioksidan enzimlerin aktiviteleri süperoksit dismutaz (SOD), katalaz (CAT), glutatyon peroksidaz (GPx) ve glutatyon (GSH) içeriği, ELISA ile belirlendiği üzere önemli ölçüde azaldı. Ayrıca, Western blot analizi, nükleer faktör-kappa B (NF-κB) ve Beclin-1'in belirgin şekilde yukarı regülasyonunu ortaya koydu ve bu da PCM maruziyetinden sonra dalak dokusunda artan inflamatuar ve otofajik aktiviteyi gösteriyor. Sodyum pentaborat ile ön tedavi, bu biyokimyasal ve moleküler değişiklikleri önemli ölçüde iyileştirdi. Bulgular genel olarak borun oksidatif stresi, inflamasyonu, apoptozu ve otofaji ile ilişkili yolları düzenleyerek parasetamol kaynaklı dalak hasarına karşı koruma sağladığını göstermektedir.

Keywords

• Antioksidan
• Apoptozis
• İnflamasyon
• Parasetamol
• Sitokin
• Sodyum Pentaborat.

Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms

Abstract

Paracetamol (PCM) is a commonly used analgesic and antipyretic drug, yet its overdose may lead to serious organ damage. One of the lesser-explored targets of PCM-induced toxicity is the spleen, a critical immune organ. Boron, a trace element with known biological benefits, has been used therapeutically since ancient times. This study was designed to evaluate the protective effects of boron, administered as sodium pentaborate (50 mg/kg and 100 mg/kg, orally), against paracetamol-induced spleen injury in rats. Male Sprague-Dawley rats were pretreated with sodium pentaborate for six days, followed by a single toxic dose of paracetamol (1 g/kg). Paracetamol exposure led to increased oxidative stress and inflammation in spleen tissue, as evidenced by elevated levels of malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and caspase-3. Additionally, the activities of key antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and the glutathione (GSH) content were significantly reduced. Furthermore, Western blot analysis revealed marked upregulation of nuclear factor-kappa B (NF-κB) and Beclin-1, indicating enhanced inflammatory and autophagic activity in spleen tissue following PCM exposure. Pretreatment with sodium pentaborate significantly ameliorated these biochemical and molecular alterations. Overall, the findings suggest that boron confers protection against paracetamol-induced splenic injury by modulating oxidative stress, inflammation, apoptosis, and autophagy-related pathways.

Keywords

• Antioxidant
• Apoptosis
• Cytokine
• Inflammation
• Paracetamol
• Sodium Pentaborate.

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