Histological Evaluation of the Protective Role of β-glucan Against Cisplatin-Induced Hepatotoxicity

Year 2024, , 38 - 43, 15.06.2024

Burcu Demirel Yılmaz , Banu Eren , Dilek Sağır , Ayşe Başardı , Sevcan Mercan

https://doi.org/10.55213/kmujens.1434724

Abstract

Cisplatin is a commonly used chemotherapeutic agent in the treatment of many cancers. The most important dose-limiting side effect is hepatotoxicity. Some studies have shown that antioxidant treatment with cisplatin reduces the toxic effect. In the present study, we were aimed to investigate the protective effects of antioxidant β-glucan on histological injury caused by cisplatin treatment in the liver. Wistar rats were randomly divided into three groups according to time of sacrifice, 7th day and 14th day (n=20 rats each). Both groups were then divided into four sub-groups Control, Cisplatin (10 mg/kg bw), β-glucan (100 mg/kg bw) and cisplatin+β-glucan (n=5 in each group). The rats were sacrificed at the 7th day and 14th day after the last injection. The liver sections were evaluated under a light microscope after the histological procedure. Histological injury caused by cisplatin in different days were evaluated as as sinusoidal congestion, hydropic degeneration, disorganization of hepatic cords, and mononuclear cellular infiltration in liver. When β-glucan was administered with cisplatin, it was determined that cellular damage caused by cisplatin decreased considerably in the liver in the different days groups. The light microscopic examination showed that the antioxidant beta-glucan protects against hepatotoxicity caused by cisplatin with its free radical scavenging effect. In conclusion, β-glucan may improve patients' quality of life by reducing cisplatin's toxicity on the liver.

Keywords

Cisplatin, β-glucan, liver, histopathology

Sisplatinin Neden Olduğu Hepatotoksisite Üzerine β-glukanın Koruyucu Rolünün Histopatolojik Olarak Değerlendirilmesi

Abstract

Sisplatin pek çok kanserin tedavisinde sıklıkla kullanılan kemoterapötik bir ajandır. En önemli doz sınırlayıcı yan etkisi hepatotoksisitedir. Bu çalışmada, sisplatin tedavisinin karaciğerde neden olduğu histolojik hasar üzerinde antioksidan β-glukanın etkilerinin araştırılması amaçlandı. Wistar ratlar sacrifiye edilecek zamana göre rastgele dört gruba ayrıldılar. Bu gruplar 1. gün, 2. gün, 7. ve 14. gün (n=20 her grupta 20 rat) olarak belirlendi. Her grupta kendi içinde Kontrol, Sisplatin (10 mg/kg), β-glukan (100 mg/kg) ve Sisplatin+β-glukan (n=5 her grupta) olmak üzere dört alt gruba ayrıldı. Ratlar son enjeksiyondan sonraki 1. gün, 2. gün, 7. gün ve 14. günde sakrifiye edildi. Histolojik prosedürün ardından karaciğer kesitleri ışık mikroskobik incelendi. Sisplatinin farklı günlerde oluşturduğu histolojik hasar sinüzoidal konjesyon, hidropik dejenerasyon, hepatik kordlarda düzensizlik ve karaciğerde mononükleer hücre infiltrasyonu olarak değerlendirildi. Sisplatin ile birlikte β-glukan uygulandığında farklı gün gruplarında sisplatinin karaciğerde neden olduğu hücresel hasarın önemli ölçüde azaldığı belirlendi. Işık mikroskobik incelemede antioksidan β-glukanın serbest radikal temizleyici etkisi ile sisplatinin neden olduğu hepatotoksisiteye karşı koruma sağladığı görüldü. Sonuç olarak β-glukan, sisplatinin karaciğer üzerindeki toksisitesini azaltarak hastaların yaşam kalitesini arttırabilir.

Keywords

Sisplatin, β-glukan, karaciğer, histopatoloji

References

• Abbasi MM, Hassanalilou T, Khordadmehr M, Vardin AM, Kohlan AB, Khalili L (2020). Effects of cornus mas fruit hydro-methanolic extract on liver antioxidants and histopathologic changes induced by Cisplatin in rats. Indian J Clinical Biochemistry, 35(2):218-224. Adam R, Bhangui P, Vibert E, Azoulay D, Pelletier G, Duclos-Vallée JC, Samuel D, Guettier C, Castaing D (2012). Resection or transplantation for early hepatocellular carcinoma in a cirrhotic liver: does size define the best oncological strategy?. Annals of Surgery, 256:883-91.
• Akaras N, Abuc OO, Koc K, Bal T, Geyikoglu H (2020). (1→3)‐β‐d‐glucan enhances the toxicity induced by Bortezomib in rat testis. J Food Biochemica, 44(3):e13155.
• Atessahin A, Yilmaz S, Karahan I, Ceribasi AO, Karaoglu A (2005). Effects of lycopene against cisplatin-induced nephrotoxicity and oxidative stress in rats. Toxicology, 212(2-3):116-23.
• Avcı A, Çetin R, Ergüder İB, Devrim E, Kılıçoğlu B (2008). Cisplatin causes oxidation in rat liver tissues: possible protective effects of antioxidant food supplementation. Turkish J Med Sci, 38(2):117-120.
• Aydogan MS, Polat A, Vardi N, Erdogan MA, Yucel A (2016). Protective effects of melatonin and β-D-glucan against acetaminophen toxicity in rats. Med Sci, 5(2):539-43.
• Bancroft JD, Stevens A (1995). Theory and practice of histological techniques, fourt edition. Churchill livingestone.
• Beretta GL, Gatti L, Corna E, Carenini N, Zunino F (2008). Defining targets of modulation of human tumor cell response to cisplatin. Journal of Inorganic Biochemistry, 102:1406-1415.
• Brown BG, Gordon S (2003). Fungal β-glucans and mammalian immunity. Immunity, 19:311-315.
• Florea AM, Busselberg D (2011). Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers (Basel), 3(1):1351-71.
• Grant DM (1991). Detoxification pathways in the liver. Journal of Inherited Metabolic Disease, 14(4):421-30.
• Hamad R, Jayakumar C, Ranganathan P, Mohamed R, El-Hamamy MMI (2015). Honey feeding protects kidney against cisplatin nephrotoxicity through suppression of inflammation. Clinical and Experimental Pharmacology and Physiology, 42(8):843-848.
• İşeri S, Ercan F, Gedik N, Yüksel M, Alican İ (2007). Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. Toxicology, 230:256-732.
• Karaduman D, Eren B, Keles ON (2010). The protective effect of Beta-1,3-D-glucan on taxol induced hepatotoxicity: a histopathological and stereological study. Drug and Chemical Toxicology, 33(1):8-16.
• Kaya K, Ciftci O, Cetin A, Tecellioğlu M, Başak N (2016). Beneficial effects of β-glucan against cisplatin side effects on the nervous system in rats. Acta Cirúrgica Brasileira, 31(3):198-205.
• Kayali H, Özdağ MF, Kahraman S, Aydin A, Gonul E (2005). The antioxidant effect of Beta-glucan on oxidative stress status in experimental spinal cord injury in rats. Pub-Med Medline, 28(4):298-302.
• Kaymak E, Ünsal M, Akın AT, Öztürk E, Ceylan T, Kuloğlu N, Karabulut D, Yakan B (2022). Protective effect of melatonin on cisplatin-induced liver injury in rats. Çukurova Medical Journal, 47(1):250-258.
• Koc A, Duru M, Ciralik H, Akcan R, Sogut S (2005). Protective agent, erdosteine, against cisplatin-induced hepatic oxidant injury in rats. Molecular Cell Biochemistry, 278(1-2):79-84.
• Kofuji K, Aoki A, Tsubaki K, Konishi M, Isobe T, Murata Y (2012). Antioxidant activity of β-glucan. ISRN Pharm, 2012:125864.
• Liao Y, Lu X, Lu C, Li G, Jin Y (2008). Selection of Agents for prevention of cisplatin-induced hepatotoxicity. Pharmacological, 57:125-131.
• Mansour HH, Hafez FH, Fahmy, NM (2006). Silymarin modulates cisplatin-induced oxidative stres and hepatotoxicity in rats. Journal Biochemical Molecular Biology, 30;39(6):656-61.
• Palipoch S, Punsawad C (2013). Biochemical and histological study of rat liver and kidney injury induced by cisplatin. Journal Toxicol Pathology, 26:293-299.
• Pınar N, Çakırca G, Hakverdi S, Kaplan M (2019). Protective effect of Alpha lipoic acid on cisplatin induced hepatotoxicity in rats. Biotechnic&Histochemistry, 95(3):219-224.
• Rabik CA, Dolan ME (2007). Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treatment Reviews, 33(1):9-23.
• Rajendrakumar T, Rao S, Satyanarayana ML, Narayanaswamy HD, Byregowda SM, Purushotham KM (2020). Cisplatin induced histopathological changes in the liver and its amelioration by Andrographis paniculata. The Pharma Innovation Journal, 9(5):46-56.
• Rajendrakumar T, Rao S, Satyanarayana ML, Narayanaswamy HD, Byregowda SM, Purushotham KM (2020). Cisplatin induced histopathological changes in the liver and its amelioration by Andrographis paniculata. The Pharma Innovation Journal, 9(5):46-56.
• Sener G, Eksioğlu Demiralp E, Çetiner M, Ercan F, Yeğen BC (2006).β-glucan ameliorates methotrexate-induced oxidative organ injury via its antioxidant and immunomodulatory effects. European J of Pharmacology, 542:170-178.
• Sener G, Toklu HZ, Cetinel Ş (2007). Beta-glucan protects against chronic nicotine-ınduced oxidative damage in kidney and bladder. Environmental Toxicology and Pharmacology, 23:25-32.
• Simsek N, Koc A, Karadeniz A, Yıldırım ME, Celik HT (2016). Ameliorative effect of selenium in cisplatin-induced testicular damage in rats. Acta Histochemica, 118(3):263-70.
• Sindhu G, Nishanthi E, Sharmila R (2015). Nephroprotective effect of vanillic acid againstcisplatin induced nephrotoxicity in wistar rats: a biochemical and molecular study. Environmental Toxicology and Pharmacology, 39(1):392-404.
• Soliman AM, Desouky S, Marzouk M, Sayed AA (2016). Origanum majorana attenuates nephrotoxicity of cisplatin anticancer drug through ameliorating oxidative stress. Nutrients, 8(5):264.
• Söğüt S, Yılmaz HR, Songur A, Güleç M, Kotuk M (2004). Sıçanlarda cisplatin ile oluşturulan nefrotoksisitede bazı metabolik enzim aktiviteleri ve bunlar Üzerine E vitaminin etkileri. Tıp Araştırmaları Dergisi, 2(1):23-28.
• Tohamy AA, Aref AM, Moneim AEA, Sayed RH (2016). Cinnamic acid attenuates cisplatin-induced hepatotoxicity and nephrotoxicity. Journal of Basic and Environmental Sciences, 3:1-9.
• Tohamy AA, El-Ghor AA, El-Nahas SM, Noshy M (2003). Beta-glucan inhibits the genotoxicity of cyclophosphamide, adriamycin and cisplatin. Mutation Research, 541(1-2):45-53.
• Toklu HZ, Şehirli AÖ, Velioğlu Oğünç A, Çetinel Ş, Şener G (2006). Acetaminophen-induced toxicity is prevented by Beta-glucan treatment in mice. Europen Journal of Pharmocology, 543:133-140.
• Wakui A, Kasai M, Konno K (1986). Randomized study of lentinan on patients with advanced gastric and colorectal cancer. Tohoku Lentinan Study Group,” Gan To Kagaku Ryoho, 13(4 Pt 1):1050-9.
• Yılmaz HR, Söğüt S, Özyurt H, Iraz M, Yıldırım Z (2004). Sıçanlarda sisplatinle oluşturulan nefrotoksisitede metabolik enzim aktivitelerine kafeik asit fenetil esterin etkisi. Van Tıp Dergisi, 11(1):1-6.
• Zicca A, Cafaggi S, Mariggio MA, Vannozzi MO, Ottone M (2002). Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in Rats. Europen Journal of Pharmacology, 442:265-272.