Melatoninin sıçanlarda cisplatin kaynaklı karaciğer hasarı üzerindeki koruyucu etkisi

Year 2022, Volume: 47 Issue: 1, 250 - 258, 31.03.2022

Emin Kaymak , Murat Ünsal , Ali Akın , Emel Öztürk , Tayfun Ceylan , Nurhan Kuloğlu , Derya Karabulut , Birkan Yakan

Abstract

Amaç: Cisplatin ile oluşturulan deneysel hepatatoksisite üzerine melatoninin koruyucu etkisini değerlendirmeyi amaçladık.
Gereç ve Yöntem: Toplam 40 adet Wistar Albino türü rat kullanıldı. Kontrol grubuna (n=10) günlük 0.1 mg / kg izotonik solüsyon (intraperitoneal) i.p. uygulandı. Cisplatin grubuna (n = 10) 5. gün tek doz i.p. Sisplatin (7 mg / kg) uygulandı. Melatonin grubuna (n = 10) günlük i.p. Melatonin (10 mg / kg) uygulandı. Cisplatin + Melatonin grubuna (n = 10) günlük i.p. Melatonin (10 mg / kg) + 5. günde tek doz i.p. Cisplatin (7mg / kg) uygulandı. Deneyin 8. günü ratlardan karaciğer dokuları histolojik ve immünohistokimyasal olarak Tümör nekrozis faktör-α (TNF-α) inceleme için alındı. Kanlardan elde edilen serumlardan da karaciğer fonksiyonu için Alanin aminotransferaz (ALT), aspartat aminotransferaz (AST), Laktat dehidrogenaz (LDH) ve albümin seviyeleri için analizler yapıldı.
Bulgular: Cisplatin uygulamasıyla birlikte karaciğer dokusu histopatolojik skorunun ve TNF-α immünoreaktivitesinin kontrol grubuna göre anlamlı olarak artış gösterdiği görülmüştür. Melatonin ile tedavi edilen grupta ise histopatolojik skorunun ve TNF-α immünoreaktivitesinin azaldığını ayrıca karaciğer fonksiyonu enzimleri olan ALT, AST ve LDH’ın cisplatin grubuna göre anlamlı şekilde azaldığını bulduk. Albümin düzeyi ise melatonin ile tedavi edilen grupta önemli bir iyileşme gösterdi.
Sonuç: Melatoninin, sisplatinin neden olduğu hepatotoksisitede inflamasyonu azaltarak ve karaciğer enzimlerindeki artışı önleyerek koruyucu rol oynayabilir.

Keywords

Cisplatin, melatonin, inflamasyon

Supporting Institution

Erciyes Üniversitesi Bilimsel Araştırma Projeleri Birimi tarafından desteklenmiştir.

Project Number

TTU-2019-9365

Protective effect of melatonin on cisplatin-induced liver injury in rats

Abstract

Purpose: We aimed to evaluate the protective effect of melatonin (Mel) on experimental hepatatoxicity induced by cisplatin (Cis).
Materials and Methods: A total of 40 Wistar Albino rats were used. Control group (n = 10) daily 0.1 mg / kg isotonic solution (intraperitoneal) i.p. was administered. Cis group (n = 10) was given a single dose of i.p. Cis (7 mg/kg) was administered. Melatonin (Mel) group (n = 10) daily i.p. Mel (10 mg / kg) was administered. Cis + Mel group (n = 10) daily i.p. Mel (10 mg / kg) + single dose i.p. Cis (7mg / kg) was administered. On the 8th day of the experiment, liver tissues of rats were collected histologically and immunohistochemically for tumor necrosis factor-α (TNF-α) analysis. Analyzes were performed for the levels of Alanine aminotransferase (ALT), aspartate aminotransferase (AST), Lactate dehydrogenase (LDH), and albumin for liver function from the serum obtained from the blood.
Results: It was observed that liver tissue histopathological score and TNF-α immunoreactivity increased significantly with cisplatin administration compared to the control group. We found that the histopathological score and TNF-α immunoreactivity were decreased in the group treated with melatonin, and the liver function enzymes ALT, AST, and LDH were significantly decreased compared to the cisplatin group. Albumin level, on the other hand, showed a significant improvement in the group treated with melatonin.
Conclusion: Melatonin may play a protective role in hepatotoxicity caused by cisplatin by reducing inflammation and preventing the increase in liver enzymes

Keywords

Cisplatin, inflammation, melatonin

Project Number

TTU-2019-9365

References

• Martins NM, Santos NA, Curti C, Bianchi ML, Santos AC. Cisplatin induces mitochondrial oxidative stress with resultant energetic metabolism impairment, membrane rigidification and apoptosis in rat liver. J Appl Toxicol. 2008;28:337-44.
• Farooqui Z, Afsar M, Rizwan S, Khan AA, Khan F. Oral administration of Nigella sativa oil ameliorates the effect of cisplatin on membrane enzymes, carbohydrate metabolism and oxidative damage in rat liver. Toxicol Rep. 2016;3:328-35.
• Palipoch S, Punsawad C. Biochemical and histological study of rat liver and kidney injury induced by Cisplatin. J Toxicol Pathol. 2013;26:293-9.
• Al-Malki AL, Sayed AA. Thymoquinone attenuates cisplatin-induced hepatotoxicity via nuclear factor kappa-β. BMC Complement Altern Med. 2014;14:282.
• Cure MC, Cure E, Kalkan Y, Kirbas A, Tumkaya L, Yilmaz A et al. Infliximab modulates cisplatin-induced hepatotoxicity in rats. Balkan Med J. 2016;33:504-11.
• Zeashan H, Amresh G, Singh S, Rao CV. Hepatoprotective and antioxidant activity of Amaranthus spinosus against CCl4 induced toxicity. J Ethnopharmacol. 2009;125:364-6.
• Amaral FGD, Cipolla-Neto J. A brief review about melatonin, a pineal hormone. Arch Endocrinol Metab. 2018;62:472-9.
• Tordjman S, Chokron S, Delorme R, Charrier A, Bellissant E, Jaafari N et al. Melatonin: pharmacology, functions and therapeutic benefits. Curr Neuropharmacol. 2017;15:434-43.
• Chen J, Xia H, Zhang L, Zhang H, Wang D, Tao X. Protective effects of melatonin on sepsis-induced liver injury and dysregulation of gluconeogenesis in rats through activating SIRT1/STAT3 pathway. Biomed Pharmacother. 2019;117:109150.
• Oleshchuk O, Ivankiv Y, Falfushynska H, Mudra A, Lisnychuk N. Hepatoprotective effect of melatonin in toxic liver injury in rats. Medicina. 2019;55:304.
• Sohail N, Hira K, Tariq A, Sultana V, Ehteshamul-Haque S. Marine macro-algae attenuates nephrotoxicity and hepatotoxicity induced by cisplatin and acetaminophen in rats. Environ Sci Pollut Res Int. 2019;26:25301-11.
• Sayan M, Karabulut D, Ozdamar S. Assessment of the protective and therapeutic effect of melatonin against thioacetamide-induced acute liver damage. J Biochem Mol Toxicol. 2020;34:e22450.
• Doğanyiğit Z, Okan A, Kaymak E, Pandır D, Silici S. Investigation of protective effects of apilarnil against lipopolysaccharide induced liver injury in rats via TLR 4/ HMGB-1/ NF-κB pathway. Biomed Pharmacother. 2020;125:109967.
• Sönmez MF, Ozdemir Ş, Guzel M, Kaymak E. The ameliorative effects of vinpocetine on apoptosis and HSP-70 expression in testicular torsion in rats. Biotech Histochem. 2017;92:92-9.
• Zhang JJ, Meng X, Li Y, Zhou Y, Xu DP, Li S et al. Effects of melatonin on liver injuries and diseases. Int J Mol Sci. 2017;18:673.
• Lv WJ, Liu C, Yu LZ, Zhou JH, Li Y, Xiong Y et al. Melatonin alleviates neuroinflammation and metabolic disorder in DSS-induced depression rats. Oxid Med Cell Longev. 2020;2020:1241894.
• Dkhil MA, Al-Quraishy S, Aref AM, Othman MS, El-Deib KM, Abdel Moneim AE. The potential role of Azadirachta indica treatment on cisplatin-induced hepatotoxicity and oxidative stress in female rats. Oxid Med Cell Longev. 2013;2013:741817.
• Sun CK, Chen CH, Chang CL, Chiang HJ, Sung PH, Chen KH et al. Melatonin treatment enhances therapeutic effects of exosomes against acute liver ischemia-reperfusion injury. Am J Transl Res. 2017;9:1543-60.
• Ebaid H, Bashandy SA, Alhazza IM, Rady A, El-Shehry S. Folic acid and melatonin ameliorate carbon tetrachloride-induced hepatic injury, oxidative stress and inflammation in rats. Nutr Metab (Lond). 2013;10:20.
• Wang H, Wei W, Shen YX, Dong C, Zhang LL, Wang NP et al. Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide. World J Gastroenterol. 2004;10:2690-6.
• Segal-Salto M, Barashi N, Katav A, Edelshtein V, Aharon A, Hashmueli S et al. A blocking monoclonal antibody to CCL24 alleviates liver fibrosis and inflammation in experimental models of liver damage. JHEP Rep. 2020;2:100064.
• Aladaileh SH, Abukhalil MH, Saghir SAM, Hanieh H, Alfwuaires MA, Almaiman AA et al. Galangin activates Nrf2 signaling and attenuates oxidative damage, inflammation, and apoptosis in a rat model of cyclophosphamide-induced hepatotoxicity. Biomolecules. 2019;9:346.
• Turan MI, Siltelioglu Turan I, Mammadov R, Altinkaynak K, Kisaoglu A. The effect of thiamine and thiamine pyrophosphate on oxidative liver damage induced in rats with cisplatin. Biomed Res Int. 2013;2013:783809.
• Zhang Y, Wei Z, Liu W, Wang J, He X, Huang H et al. Melatonin protects against arsenic trioxide-induced liver injury by the upregulation of Nrf2 expression through the activation of PI3K/AKT pathway. Oncotarget. 2017;8:3773-80.
• Spinella R, Sawhney R, Jalan R. Albumin in chronic liver disease: structure, functions and therapeutic implications. Hepatol int. 2016;10:124-32.
• Montasser AOS, Saleh H, Ahmed-Farid OA, Saad A, Marie MS. Protective effects of Balanites aegyptiaca extract, Melatonin and Ursodeoxycholic acid against hepatotoxicity induced by Methotrexate in male rats. Asian Pac J Trop Med. 2017;10:557-65.
• Ali SA, Aly HF, Faddah LM, Zaidi ZF. Dietary supplementation of some antioxidants against hypoxia. World J Gastroenterol. 2012;18:6379-86.