Research Article
BibTex RIS Cite

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

Year 2025, Volume: 14 Issue: 2, 180 - 186, 24.12.2025
https://doi.org/10.31196/huvfd.1739381

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.

References

  • Andrabi SW, Saini P, Joshi M, Mehta P, Makker GC, Mishra G, Rajender S, 2022: HCG therapy in azoospermic men with lower or borderline testosterone levels and the prognostic value of Y-deletion analysis in its outcome. Andrologia, 54, e14251.
  • Ayenew KD, Wasihun Y, 2023: Hepatoprotective effect of methanol extract of Agave americana leaves on paracetamol-induced hepatotoxicity in Wistar albino rats. BMC Complement Med Ther, 23, 1–8.
  • Dogan T, Yildirim BA, Kapakin KAT, 2024: Investigation of the effects of crocin on inflammation, oxidative stress, apoptosis, NF-κB, TLR-4 and Nrf-2/HO-1 pathways in gentamicin-induced nephrotoxicity in rats. Environ Toxicol Pharmacol, 106, 104374.
  • Feki F, Mahmoudi A, Denev P, Feki I, Ognyanov M, Georgiev Y, Choura S, Chamkha M, Trendafilova A, Sayadi S, 2022: A jojoba (Simmondsia chinensis) seed cake extracts express hepatoprotective activity against paracetamol-induced toxicity in rats. Biomed Pharmacother, 153, 113371.
  • Henneh IT, Ahlidja W, Alake J, Kwabil A, Ahmed MA, Kyei-Asante B, Adinortey MB, Ekor M, Armah FA, 2022: Ziziphus abyssinica root bark extract ameliorates paracetamol-induced liver toxicity in rats possibly via the attenuation of oxidative stress. Toxicol Rep, 9, 1929–1937. https://doi.org/10.1016/j.toxrep.2022.10.012
  • Hongslo JK, Smith CV, Brunborg G, Søderlund EJ, Holme JÅ, 1994: Genotoxicity of paracetamol in mice and rats. Mutagenesis, 9, 93–100. https://doi.org/10.1093/mutage/9.2.93
  • Ince S, Kucukkurt I, Demirel HH, Acaroz DA, Akbel E, Cigerci IH, 2014: Protective effects of boron on cyclophosphamide-induced lipid peroxidation and genotoxicity in rats. Chemosphere, 108, 197–204. https://doi.org/10.1016/j.chemosphere.2014.01.038
  • Ince S, Kucukkurt I, Demirel HH, Arslan-Acaroz D, Varol N, 2020: Boron, a trace mineral, alleviates gentamicin-induced nephrotoxicity in rats. Biol Trace Elem Res, 195, 515–524. https://doi.org/10.1007/s12011-019-01875-4
  • Islam MT, Quispe C, Islam MA, Ali ES, Saha S, Asha UH, Mondal M, Razis AFA, Sunusi U, Kamal RM, Kumar M, Sharifi-Rad J, 2021: Effects of nerol on paracetamol-induced liver damage in Wistar albino rats. Biomed Pharmacother, 140, 111732. https://doi.org/10.1016/j.biopha.2021.111732
  • Jaeschke H, McGill MR, Ramachandran A, 2012: Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity. Drug Metab Rev, 44, 88–106. https://doi.org/10.3109/03602532.2011.602688
  • Karatekeli S, Demirel HH, Zemheri-Navruz F, Ince S, 2023a: Boron exhibits hepatoprotective effect together with antioxidant, anti-inflammatory, and anti-apoptotic pathways in rats exposed to aflatoxin B1. J Trace Elem Med Biol, 77, 127127. https://doi.org/10.1016/j.jtemb.2023.127127
  • Karatekeli S, Demirel HH, Zemheri-Navruz F, Ince S, 2023b: Boron exhibits hepatoprotective effect together with antioxidant, anti-inflammatory, and anti-apoptotic pathways in rats exposed to aflatoxin B1. J Trace Elem Med Biol, 77, 127127. https://doi.org/10.1016/j.jtemb.2023.127127
  • McGill MR, Williams CD, Xie Y, Ramachandran A, Jaeschke H, 2012: Acetaminophen-induced liver injury in rats and mice: Comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. Toxicol Appl Pharmacol, 264, 387–394. https://doi.org/10.1016/j.taap.2012.08.015
  • Nouioura G, Kettani T, Tourabi M, Elousrouti LT, Al kamaly O, Alshawwa SZ, Shahat AA, Alhalmi A, Lyoussi B, Derwich E, 2023: The protective potential of Petroselinum crispum (Mill.) Fuss. on paracetamol-induced hepato-renal toxicity and antiproteinuric effect: A biochemical, hematological, and histopathological study. Medicina, 59, 1814. https://doi.org/10.3390/medicina59101814
  • Rousta AM, Mirahmadi SMS, Shahmohammadi A, Mehrabi Z, Fallah S, Baluchnejadmojarad T, Roghani M, 2022: Therapeutic potential of isorhamnetin following acetaminophen-induced hepatotoxicity through targeting NLRP3/NF-κB/Nrf2. Drug Res, 72, 245–254. https://doi.org/10.1055/a-1792-2678
  • Senocak AE, Utlu N, Kurt S, Kucukler S, Kandemir FM, 2024: Sodium pentaborate prevents acetaminophen-induced hepatorenal injury by suppressing oxidative stress, lipid peroxidation, apoptosis and inflammatory cytokines in rats. Biol Trace Elem Res, 202, 1164–1173.
  • Tejo J, 2021: Curcumin, antioxidant activity, and paracetamol toxicity. In: Toxicology: Oxidative Stress and Dietary Antioxidants, 469–477. https://doi.org/10.1016/B978-0-12-819092-0.00046-7
  • Xiao Q, Zhao Y, Ma L, Piao R, 2022: Orientin reverses acetaminophen-induced acute liver failure by inhibiting oxidative stress and mitochondrial dysfunction. J Pharmacol Sci, 149, 11–19. https://doi.org/10.1016/j.jphs.2022.01.012
  • Zubairu Aliyu S, Simeon Joseph O, Tosin Joseph O, Ayodele Festus O, Oyepata Simeon J, Irabor I, Opeyemi Tosin J, 2021: Effect of Anacardium occidentale fruit juice extract on haematological parameters and spleen of paracetamol-induced injury in albino rats.

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

Year 2025, Volume: 14 Issue: 2, 180 - 186, 24.12.2025
https://doi.org/10.31196/huvfd.1739381

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.

References

  • Andrabi SW, Saini P, Joshi M, Mehta P, Makker GC, Mishra G, Rajender S, 2022: HCG therapy in azoospermic men with lower or borderline testosterone levels and the prognostic value of Y-deletion analysis in its outcome. Andrologia, 54, e14251.
  • Ayenew KD, Wasihun Y, 2023: Hepatoprotective effect of methanol extract of Agave americana leaves on paracetamol-induced hepatotoxicity in Wistar albino rats. BMC Complement Med Ther, 23, 1–8.
  • Dogan T, Yildirim BA, Kapakin KAT, 2024: Investigation of the effects of crocin on inflammation, oxidative stress, apoptosis, NF-κB, TLR-4 and Nrf-2/HO-1 pathways in gentamicin-induced nephrotoxicity in rats. Environ Toxicol Pharmacol, 106, 104374.
  • Feki F, Mahmoudi A, Denev P, Feki I, Ognyanov M, Georgiev Y, Choura S, Chamkha M, Trendafilova A, Sayadi S, 2022: A jojoba (Simmondsia chinensis) seed cake extracts express hepatoprotective activity against paracetamol-induced toxicity in rats. Biomed Pharmacother, 153, 113371.
  • Henneh IT, Ahlidja W, Alake J, Kwabil A, Ahmed MA, Kyei-Asante B, Adinortey MB, Ekor M, Armah FA, 2022: Ziziphus abyssinica root bark extract ameliorates paracetamol-induced liver toxicity in rats possibly via the attenuation of oxidative stress. Toxicol Rep, 9, 1929–1937. https://doi.org/10.1016/j.toxrep.2022.10.012
  • Hongslo JK, Smith CV, Brunborg G, Søderlund EJ, Holme JÅ, 1994: Genotoxicity of paracetamol in mice and rats. Mutagenesis, 9, 93–100. https://doi.org/10.1093/mutage/9.2.93
  • Ince S, Kucukkurt I, Demirel HH, Acaroz DA, Akbel E, Cigerci IH, 2014: Protective effects of boron on cyclophosphamide-induced lipid peroxidation and genotoxicity in rats. Chemosphere, 108, 197–204. https://doi.org/10.1016/j.chemosphere.2014.01.038
  • Ince S, Kucukkurt I, Demirel HH, Arslan-Acaroz D, Varol N, 2020: Boron, a trace mineral, alleviates gentamicin-induced nephrotoxicity in rats. Biol Trace Elem Res, 195, 515–524. https://doi.org/10.1007/s12011-019-01875-4
  • Islam MT, Quispe C, Islam MA, Ali ES, Saha S, Asha UH, Mondal M, Razis AFA, Sunusi U, Kamal RM, Kumar M, Sharifi-Rad J, 2021: Effects of nerol on paracetamol-induced liver damage in Wistar albino rats. Biomed Pharmacother, 140, 111732. https://doi.org/10.1016/j.biopha.2021.111732
  • Jaeschke H, McGill MR, Ramachandran A, 2012: Oxidant stress, mitochondria, and cell death mechanisms in drug-induced liver injury: Lessons learned from acetaminophen hepatotoxicity. Drug Metab Rev, 44, 88–106. https://doi.org/10.3109/03602532.2011.602688
  • Karatekeli S, Demirel HH, Zemheri-Navruz F, Ince S, 2023a: Boron exhibits hepatoprotective effect together with antioxidant, anti-inflammatory, and anti-apoptotic pathways in rats exposed to aflatoxin B1. J Trace Elem Med Biol, 77, 127127. https://doi.org/10.1016/j.jtemb.2023.127127
  • Karatekeli S, Demirel HH, Zemheri-Navruz F, Ince S, 2023b: Boron exhibits hepatoprotective effect together with antioxidant, anti-inflammatory, and anti-apoptotic pathways in rats exposed to aflatoxin B1. J Trace Elem Med Biol, 77, 127127. https://doi.org/10.1016/j.jtemb.2023.127127
  • McGill MR, Williams CD, Xie Y, Ramachandran A, Jaeschke H, 2012: Acetaminophen-induced liver injury in rats and mice: Comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity. Toxicol Appl Pharmacol, 264, 387–394. https://doi.org/10.1016/j.taap.2012.08.015
  • Nouioura G, Kettani T, Tourabi M, Elousrouti LT, Al kamaly O, Alshawwa SZ, Shahat AA, Alhalmi A, Lyoussi B, Derwich E, 2023: The protective potential of Petroselinum crispum (Mill.) Fuss. on paracetamol-induced hepato-renal toxicity and antiproteinuric effect: A biochemical, hematological, and histopathological study. Medicina, 59, 1814. https://doi.org/10.3390/medicina59101814
  • Rousta AM, Mirahmadi SMS, Shahmohammadi A, Mehrabi Z, Fallah S, Baluchnejadmojarad T, Roghani M, 2022: Therapeutic potential of isorhamnetin following acetaminophen-induced hepatotoxicity through targeting NLRP3/NF-κB/Nrf2. Drug Res, 72, 245–254. https://doi.org/10.1055/a-1792-2678
  • Senocak AE, Utlu N, Kurt S, Kucukler S, Kandemir FM, 2024: Sodium pentaborate prevents acetaminophen-induced hepatorenal injury by suppressing oxidative stress, lipid peroxidation, apoptosis and inflammatory cytokines in rats. Biol Trace Elem Res, 202, 1164–1173.
  • Tejo J, 2021: Curcumin, antioxidant activity, and paracetamol toxicity. In: Toxicology: Oxidative Stress and Dietary Antioxidants, 469–477. https://doi.org/10.1016/B978-0-12-819092-0.00046-7
  • Xiao Q, Zhao Y, Ma L, Piao R, 2022: Orientin reverses acetaminophen-induced acute liver failure by inhibiting oxidative stress and mitochondrial dysfunction. J Pharmacol Sci, 149, 11–19. https://doi.org/10.1016/j.jphs.2022.01.012
  • Zubairu Aliyu S, Simeon Joseph O, Tosin Joseph O, Ayodele Festus O, Oyepata Simeon J, Irabor I, Opeyemi Tosin J, 2021: Effect of Anacardium occidentale fruit juice extract on haematological parameters and spleen of paracetamol-induced injury in albino rats.
There are 19 citations in total.

Details

Primary Language English
Subjects Veterinary Biochemistry
Journal Section Research Article
Authors

Tuba Karaaslan 0000-0003-4039-3497

Necati Utlu 0000-0001-6354-6922

Submission Date July 10, 2025
Acceptance Date November 29, 2025
Publication Date December 24, 2025
Published in Issue Year 2025 Volume: 14 Issue: 2

Cite

APA Karaaslan, T., & Utlu, N. (2025). Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms. Harran University Journal of the Faculty of Veterinary Medicine, 14(2), 180-186. https://doi.org/10.31196/huvfd.1739381
AMA Karaaslan T, Utlu N. Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms. Harran Univ Vet Fak Derg. December 2025;14(2):180-186. doi:10.31196/huvfd.1739381
Chicago Karaaslan, Tuba, and Necati Utlu. “Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms”. Harran University Journal of the Faculty of Veterinary Medicine 14, no. 2 (December 2025): 180-86. https://doi.org/10.31196/huvfd.1739381.
EndNote Karaaslan T, Utlu N (December 1, 2025) Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms. Harran University Journal of the Faculty of Veterinary Medicine 14 2 180–186.
IEEE T. Karaaslan and N. Utlu, “Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms”, Harran Univ Vet Fak Derg, vol. 14, no. 2, pp. 180–186, 2025, doi: 10.31196/huvfd.1739381.
ISNAD Karaaslan, Tuba - Utlu, Necati. “Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms”. Harran University Journal of the Faculty of Veterinary Medicine 14/2 (December2025), 180-186. https://doi.org/10.31196/huvfd.1739381.
JAMA Karaaslan T, Utlu N. Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms. Harran Univ Vet Fak Derg. 2025;14:180–186.
MLA Karaaslan, Tuba and Necati Utlu. “Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Mechanisms”. Harran University Journal of the Faculty of Veterinary Medicine, vol. 14, no. 2, 2025, pp. 180-6, doi:10.31196/huvfd.1739381.
Vancouver Karaaslan T, Utlu N. Sodium Pentaborate Attenuates Paracetamol-Induced Splenic Toxicity via Antioxidant, Anti-inflammatory, and Anti-apoptotic Mechanisms. Harran Univ Vet Fak Derg. 2025;14(2):180-6.