Investigation of the Effects of Boric Acid Used in the Treatment of Rat Models with Knee Osteoarthritis Induced by Monosodium Iodoacetate on Liver Tissue

Abstract

Osteoarthritis (OA) is a significant joint disease that can affect the health of individuals in many sectors. Although OA is primarily known as a joint disease in the field of health, it can also cause damage to organs such as the liver due to the systemic inflammatory reactions (SIRS) it triggers. Boric acid (BA), which has been the subject of many studies and has been shown to have anti-inflammatory, anti-apoptotic, antimicrobial, and anticancer properties, is widely used in various areas of the healthcare sector. In this study conducted for this purpose, the protective effect of BA against liver damage caused by OA was investigated. A total of 28 rats were divided into four groups, each consisting of 7 rats. Except for the control group, all animals were induced with monosodium iodoacetate (MIA) to develop OA, and then rats were administered doses of BA ranging 4 and 10 mg/kg for 21 days. In histopathological examinations, severe hepatitis and degenerative changes were observed in the liver tissue of the OA-induced group, while it was found that BA application reduced these damages dose-dependently. Similarly, in immunohistochemical analyses, it was observed that OA induction significantly increased the expression levels of TNF-α, IL-1β, iNOS, and MMP-13 in the liver, but in the groups treated with BA, this expression level significantly decreased depending on the dose. This study observed that BA exhibited anti-inflammatory properties and had a protective effect on liver tissue against SIRS caused by OA.

Keywords

• Boric acid
• Histopathology
• Immunohistochemistry
• Monosodium iodoacetate
• Osteoarthritis

Monosodyum İyodoasetat ile Oluşturulan Diz Osteoartriti Olan Sıçan Modellerinin Tedavisinde Kullanılan Borik Asitin Karaciğer Dokusu Üzerine Etkilerinin Araştırılması

Abstract

Osteoartrit (OA), bireylerin sağlığını birçok sektörde etkileyebilen önemli bir eklem hastalığıdır. OA sağlık alanında öncelikle bir eklem hastalığı olarak bilinse de tetiklediği sistemik inflamatuar reaksiyonlar (SIRS) nedeniyle karaciğer gibi organlarda da hasara yol açabilmektedir. Birçok çalışmaya konu olan ve anti-enflamatuar, anti-apoptotik, anti-mikrobiyal ve anti-kanser özelliklere sahip olduğu gösterilen borik asit (BA), sağlık sektörünün çeşitli alanlarında yaygın olarak kullanılmaktadır. Bu amaçla yapılan bu çalışmada, BA'nın OA'nın neden olduğu karaciğer hasarına karşı koruyucu etkisi araştırılmıştır. Toplam 28 rat, her biri 7 rattan oluşan dört gruba ayrılmıştır. Kontrol grubu hariç, tüm hayvanlar monosodyum iyodoasetat (MIA) ile indüklenerek OA geliştirilmiş ve ardından ratlara 21 gün boyunca 4 ve 10 mg/kg dozlarda BA uygulanmıştır. Histopatolojik incelemelerde, OA oluşturulan grubun karaciğer dokusunda şiddetli hepatit ve dejeneratif değişiklikler gözlenirken, BA uygulamasının bu hasarları doza bağlı olarak azalttığı tespit edilmiştir. Benzer şekilde, immünohistokimyasal analizlerde, OA indüksiyonunun karaciğerde TNF-α, IL-1β, iNOS ve MMP-13 ekspresyon seviyelerini önemli ölçüde artırdığı, ancak BA ile tedavi edilen gruplarda bu ekspresyon seviyesinin doza bağlı olarak önemli ölçüde azaldığı gözlenmiştir. Bu çalışma, BA'nın anti-inflamatuar özellikler sergilediğini ve OA'nın neden olduğu SIRS'e karşı karaciğer dokusu üzerinde koruyucu bir etki gösterdiğini gözlemledi.

Keywords

• Borik asit
• histopatoloji
• immünohistokimya
• Monosodium iodoacetate
• Osteoartritis

References

1. Acaroz U, Kara R, Gurler Z, Ince S, Demirel HH, Acaroz DA Kucukkurt I, Eryavuz A, Varol N, Zhu K, 2019: Bisphenol-A induced oxidative stress, inflammatory gene expression, and metabolic and histopathological changes in male Wistar albino rats: protective role of boron. Tox Res, 8(2), 262-269.
2. Başbuğ M, Yıldar M, Yaman I, Özkan ÖF, Akşit H, Cavdar F, Sunay FB, Ozyıgıt MO, Derici H, 2015: Effects of boric acid in an experimental rat model of hepatic ischemia-reperfusion injury. Acta Med Mediterr, 31, 1067.
3. Başkan S, Kanak EK, Yılmaz SÖ, 2022: Borun Antimikrobiyel Etkileri ve Gıdalarda Koruyucu Olarak Kullanım Olanaklarının Değerlendirilmesi. Gıda, 47(3), 399-407.
4. Cengiz M, 2018: Boric acid protects against cyclophosphamide-induced oxidative stress and renal damage in rats. CBM, 64(12), 11-14.
5. Cengiz M, Yildiz SC, Demir C, Şahin İK, Teksoy Ö, Ayhanci A, 2019: Hepato-preventive and anti-apoptotic role of boric acid against liver injury induced by cyclophosphamide. J Trace Elem Med Biol, 53, 1-7.
6. Chen DI, Shen J, Zhao W, Wang T, Han L, Hamilton JL, Im H, 2017: Osteoarthritis: toward a comprehensive understanding of pathological mechanism. Bone Res, 5(1), 1-13.
7. Crockett ET, Galligan JJ, Uhal BD, Harkema J, Roth R, Pandya K, 2006: Protection of early phase hepatic ischemia-reperfusion injury by cholinergic agonists. BMC Clinic Patho, 6(1), 1-13.
8. Cui A, Li H, Wang D, Zhong J, Chen Y, Lu H, 2020: Global, regional prevalence, incidence and risk factors of knee osteoarthritis in population-based studies. eClinicalMedicine, 29, 100587.

9. Dai LL, Gong JP, Zuo GQ, Wu CX, Shi YJ, Li XH, Peng Y, Deng W, Li SW, Liu C.A, 2003: Synthesis of endotoxin receptor CD14 protein in Kupffer cells and its role in alcohol-induced liver disease. WJG, 9(3), 622.
10. Fonsi M, El Amrani AI, Gervais F, Vincent P, 2020: Intra-articular hyaluronic acid and chondroitin sulfate: pharmacokinetic investigation in osteoarthritic rat models. CTR, 92, 100573.
11. Ince S, Keles H, Erdogan M, Hazman O, Kucukkurt I, 2012: Protective effect of boric acid against carbon tetrachloride–induced hepatotoxicity in mice. Drug Chem Toxicol, 35(3), 285-292.
12. 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.
13. Iskender H, Dokumacioglu E, Terim Kapakin KA, Yenice G, Mohtare B, Bolat I, Hayirli A, 2022: Effects of oleanolic acid on inflammation and metabolism in diabetic rats. Bio and Histo, 97(4), 269-276.
14. Kılıçaslan C, 2020: Borun Stratejik ve Ekonomik Önemi. Doktora tezi, Costa Rica Universidad Empresarial De Costa Rica (Unem), İstanbul.
15. Kuyinu EL, Narayanan G, Nair LS, Laurencin CT, 2016: Animal models of osteoarthritis: classification, update, and measurement of outcomes. J Orthop Surg Res, 11(1), 1-27.
16. Molnar V, Matisic V, Kodvanj I, Bjelica R, Jelec Z, Hudetz D, Rod E, Cukelj F, Vrdoljak T, Vidovic D, Staresinic M, Sabalic S, Dobricic B, Petrovic T, Anticevic D, Boric I, Kosir R, Primorac D, 2021: Cytokines and chemokines involved in osteoarthritis pathogenesis. Int J Mol Sci, 22(17), 9208.
17. Primorac D, Molnar V, Rod E, Jelec Z, Cukelj F, Matisic V, Vrdoljak T, Hudetz D, Hajsok H, Boric I, 2020: Knee Osteoarthritis: A Review of Pathogenesis and State-Of-The-Art Non-Operative Therapeutic Considerations. Genes, 11(8), 854.
18. Sogut I, Paltun SO, Tuncdemir M, Ersoz M, Hurdag C, 2018: The antioxidant and antiapoptotic effect of boric acid on hepatoxicity in chronic alcohol-fed rats. J Physiol Pharmacol, 96(4), 404-411.
19. Söğüt Ö, Acar O, 2020: Bor ve sağlık. Lit Ecz Bil Derg, 9(1), 11-7.
20. Stammers T, Sibbald B, Freeling P, 1992: Efficacy of cod liver oil as an adjunct to non-steroidal anti-inflammatory drug treatment in the management of osteoarthritis in general practice. ARD, 51(1), 128-129.
21. Steels E, Venkatesh R, Steels E, Vitetta G, Vitetta L, 2019: A double-blind randomized placebo-controlled study assessing safety, tolerability and efficacy of palmitoylethanolamide for symptoms of knee osteoarthritis. Inflammopharmacology, 27, 475-485.
22. Şaylı BS, 2000: İnsan Sağlığı ve Bor Mineralleri. AÜ Tıp Fakültesi-Eti Holding Araştırma Projeleri. Ankara. Mayıs.
23. TMMOB 2016. Bor Raporu, ISBN 978-605-01- 0883-5. 2016. Ankara.
24. Yildar M, Aksit H, Korkut O, Ozyigit MO, Sunay B, Seyrek K, 2014: Protective effect of 2-aminoethyl diphenylborinate on acute ischemia–reperfusion injury in the rat kidney. J Surg Res, 187(2), 683-689.