PROTECTIVE EFFECT OF NIGELLA SATIVA OIL ON CARBOPLATIN INDUCED NEPHROTOXICITY IN RATS

Year 2020, Volume: 21 Issue: 3, 236 - 243, 01.07.2020

Züleyha Erişgin , Melahat Atasever , Muserref Seyma Ceyhan Suna Omeroglu Kadir Cetinkaya

https://doi.org/10.18229/kocatepetip.581590

Abstract

OBJECTIVE: Carboplatin is a commonly used chemotherapeutic agent. Kidneys are an important organ affected by the adverse effects of chemotherapeutic agents. This study aimed to investigate the protective effect of Nigella sativa oil (NSO) against kidney damage due to carboplatin exposure.
MATERIAL AND METHODS: All animals (n=24 female wistar-albino rats) were divided into four groups; 4 ml/kg saline was intraperitoneally (i.p.) administered on day one and two in the first group. 4 ml/kg NSO on day one and 4 ml/kg saline on day two was i.p. administered in the second group.4 ml/kg saline on day one and 80 mg/kg carboplatin on day two was i.p. administered in the third group.4 ml/kg NSO on day oneand 80 mg/kg carboplatin on day two was i.p. administered inthe fourth group. Rats were sacrificed at the end of day two and renal tissues were fixed in neutral formalin. Histopathologicchanges and apoptotic index (AI) were evaluated.
RESULTS: While an increase was observed in the apoptotic index of carboplatin+saline group compared to the control group, no significant differences were found in the carboplatin+saline and carboplatin+NSO group. In the histopathological evaluation, degeneration in the proximal and distal tubular epithelium and glomerular capillary glomus bodies, congestion in the vascular formations between the tubules, increase in collagen fiber density in the tunica adventitia of intraglomerular, preglomerular, intertubular and vascular formations, and sporadic basal disintegration due to Periodic Acid Schiff (PAS) reaction were observed in the carboplatin+saline group. In the carboplatin+NSO group, degenerative changes in some areas of tubular structures continued while it was observed that glomerular structures were more regular. It was observed that sclerotic change was fewer in the carboplatin+NSO group than in the carboplatin+saline group. It drew attention that basal membranes were more regular in the carboplatin-nigella sativa oil group as a result of PAS reaction.
CONCLUSIONS: NSO, is used as a spice, may have a protective effect on carboplatin induced nephrotoxicity.

Keywords

Apoptosis, Carboplatin, Kidney, Nigella Sativa Oil, Rat

Supporting Institution

-

Project Number

-

Thanks

-

SIÇANLARDA KARBOPLATİN İLE İNDÜKLENEN NEFROTOKSİSİTE ÜZERİNE NİGELLA SATİVA YAĞININ KORUYUCU ETKİLERİ

Abstract

AMAÇ: Karboplatin yaygın kullanılan bir kemoteröpatik ajandır. Böbrekler kemoteröpatiklerin yan etkilerinden etkilenen önemli organlardır. Bu çalışmanın amacı karboplatin kullanımına bağlı oluşan böbrek hasarına karşı Nigella sativa yağının (NSY) koruyucu etkisini araştırmaktır.
GEREÇ VE YÖNTEM: Tüm hayvanlar (n=24 dişi wistar-albino sıçan) 4 gruba bölündü; birinci grupta 4 ml/kg serum fizyolojik (SF) 1 ve 2.gün uygulandı. İkinci gruba ilk gün 4 ml/kg NSY ve 4 ml/kg SF 2. Gün i.p. verildi. Üçüncü gruba 1.gün 4 ml/kg SF ve 2.gün ise karboplatin 80 mg/kg i.p. uygulandı. Dördüncü gruba 1.gün NSY ve 2. gün ise karboplatin 80 mg/kg i.p. uygulandı. İkinci günün sonunda sıçanlar sakrifiye edildi ve böbrek dokuları nötral formalin ile fikse edildi. Histopatolojik değişiklikler ve apoptotik index (AI) değerlendirildi.
BULGULAR: Apoptotik indexte, karboplatin+SF grubunda kontrol grubuna göre artış görülürken, karboplatin+ NSY grubu ile anlamlı bir fark görülmemiştir. Histopatolojik değerlendirmede ise; Karboplatin+SF grubunda proksimal ve distal tubul epitelinde, glomerular kapiller yumaklarında dejenerasyon, tubuller arasında bulunan vasküler oluşumlarda konjesyon, intraglomerular, periglomerular, tubuller arası ve vasküler oluşumların tunika adventisyasında kollagen lif yoğunluğunda artış, Periyodik Asit Schiff (PAS) reaksiyonu sonucu yer yer basal membran bütünlüğünün bozulduğu görülmüştür. Karboplatin+ NSY verilen grupta ise bazı alanlardaki tubul yapılarında dejeneratif değişikliklerin devam ettiği görülürken glomerul yapılarının daha düzenli olduğu gözlemlenmiştir. Karboplatin+ NSY verilen grupta karboplatin+SF verilen gruba göre sklerotik değişimlerin daha az olduğu gözlendi. PAS reaksiyon sonucu karboplatin+ NSY verilen grupta basal membranların daha düzenli bir yapıda olduğu görüldü.
SONUÇ: Baharat olarak da kullanılan nigella sativanın karboplatin ile indüklenen nefrotoksisite üzerine koruyucu etkileri olabilir.

Keywords

Apoptozis, Böbrek, Karboplatin, Nigella Sativa Yağı, Sıçan

Project Number

-

References

• 1.Chen X, Wang J, Fu Z, Zhu B, Wang J, Guan S, Hua Z. Curcumin activates DNA repair pathway in bone marrow to improve carboplatin-induced myelosuppression. ScieNTific RePortS 2017; 7:17724.
• 2.Tanley SWM, Diederichs K, KroonBatenburg LM. J., Levy C, Schreurs AMM, Helliwell JR.Carboplatin binding to histidine. Acta Cryst.2014; 70: 1135–1142.
• 3.Rajeswarana A, Trojanb A, Burnanda B, Giannelli M. Efficacy and side effects of cisplatin- and carboplatin-based doublet chemotherapeutic regimens versus non-platinum-based doublet chemotherapeutic regimens as first line treatment of metastatic non-small cell lung carcinoma: A systematic review of randomized controlled trials. Lung Cancer 2008; 59: 1—11.
• 4.Matsuoka A, Ando Y. Nephropathy in Patients Undergoing Cancer Drug Therapy - Platinum Derivatives (Cisplatin and Carboplatin). Gan To Kagaku Ryoho 2017; 44(3):200-203.
• 5.Sharbaf FG, Farhangi H, Assadi F. Prevention of Chemotherapy-Induced Nephrotoxicity in Children with Cancer .Int J Prev Med 2017; 8: 76.
• 6.Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat Rev 1995; 21(1): 33-64.
• 7.Lameire N, Kruse V, Rottey S. Nephrotoxicity of anticancer drugs an underestimated problem? Acta Clin Belg 2011; 66(5):337-45.
• 8.Rabik CA, Dolan ME. Molecular mechanisms of resistance and toxicity associated with platinating agents. Cancer Treat Rev 2017; 33; 1:9-23.
• 9.Fuchs-Tarlovsky V. Role of antioxidants in cancer therapy. Nutrition 2013; 29 (1) 15-21.
• 10.Langer T, am Zehnhoff-Dinnesen A, Radtke S, Meitert J, Zolk O. Understanding platinum- induced ototoxicity. Trends Pharmacol Sci 2017; 34(8):458-69.
• 11. Khader M, Eckl PM. Thymoquinone: an emerging natural drug with a wide range of medical applications. Iran J Basic Med Sci.2014;17(12):950-7.
• 12.Eid AM, Elmarzugi NA, Abu Ayyash LM, Sawafta MN, Daana HI. A Review on the Cosmeceutical and External Applications of Nigella sativa. J Trop Med. 2017; 7092514.
• 13.Khan MA1, Chen HC, Tania M, Zhang DZ. Anticancer activities of Nigella sativa (black cumin). Afr J Tradit Complement Altern Med. 2011; 8(5):226-32.
• 14. Hosseinian S, Ebrahimzadeh Bideskan A, Shafei MN, Sadeghnia HR, Soukhtanloo M, Shahraki S, Samadi Noshahr Z, Khajavi Rad A. Nigella sativa extract is a potent therapeutic agent for renal inflammation, apoptosis, and oxidative stress in a rat model of unilateral ureteral obstruction. Phytother Res. 2018;32(11):2290-2298.
• 15.Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, Sisakhtnezhad S. Thymoquinone and its therapeutic potentials. Pharmacol Res 2015; 95-96:138-58.
• 16.Mollazadeh H, Hosseinzadeh H, 2014. The protective effect of Nigella sativa against liver injury: a review. Iran J Basic Med Sci 2014; 17 (12): 958-966.
• 17.Ming M, Ma ZL , Xu YT , Sun FY, Cui XH. Carboplatin-based Nanomedicine to Enhance the Anticancer Effect in SK-NEP-1 WilmsꞌTumor Cells. Iran J Pharm Res 2017;16(4):1305- 1311.
• 18.Ruggiero A, Ferrara P, Attinà G, Rizzo D, Riccardi R. Renal toxicity and chemotherapy in children with cancer. Br J Clin Pharmacol 2017; 83(12):2605-2614.
• 19. Jeyabalan N, Hirte HW, Moens F. Treatment of advanced ovarian carcinoma with carboplatin and paclitaxel in a patient with renal failure. Int J Gynecol Cancer 2000; 10(6):463-468.
• 20.Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res 2003; 17(4):299-305.
• 21.Havakhah S, Sadeghnia HR, Hajzadeh MA, Roshan NM, Shafiee S, Hosseinzadeh H, Mohareri N, Rad AK. Effect of Nigella sativa on ischemia-reperfusion induced rat kidney damage. Iran J Basic Med Sci 2014; 17(12):986-92.
• 22. Al-Gayyar MM, Hassan HM, Alyoussef A, Abbas A, Darweish MM, El-Hawwary AA. Nigella sativa oil attenuates chronic nephrotoxicity induced by oral sodium nitrite: Effects on tissue fibrosis and apoptosis. Redox Re 2016;. 21(2):50-60.
• 23.Dajani EZ, Shahwan TG, Dajani NE. Overview of the preclinical pharmacological properties of Nigella sativa (black seeds): a complementary drug with historical and clinical significance. J Physiol Pharmacol 2016; 67(6):801-817.
• 24. Elsherbiny NM, Maysarah NM, El-Sherbiny M, Al-Gayyar MM. Renal protective effects of thymoquinone against sodium nitrite-induced chronic toxicity in rats: Impact on inflammation and apoptosis. Life Sciences 2017; 180:1–8.
• 25.Farooqui Z, Shahid F, Khan AA, Khan F. Oral administration of Nigella sativa oil and thymoquinone attenuates long term cisplatin treatment induced toxicity and oxidative damage in rat kidney.Biomed Pharmacother 2017; 96:912-923.
• 26.Elsherbiny NM, El-Sherbiny M. Thymoquinone attenuates Doxorubicin-induced nephrotoxicity in rats: Role of Nrf2 and NOX4. Chem Biol Interact 2014; 5; 223:102-8.
• 27. Yaman I, Balikci E. Protective effects of nigella sativa against gentamicin-induced nephrotoxicity in rats.Exp Toxicol Pathol 2010; 62(2):183-90.
• 28.Ansari ZM, Nasiruddin M, Khan RA, Haque SF. Protective role of Nigella sativa in diabetic nephropathy: A randomized clinical trial. Saudi J Kidney Dis Transpl 2017; 28(1):9-14.