The protective effect of Nigella sativa against cisplatin-induced nephrotoxicity in rats

Document Type : Original Research Article

Authors

1 Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

2 Neurogenic Inflammation Research Center, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

3 Neurocognitive Research Center, Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

4 Departmant of Pathology, Qaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.

Abstract

Objective: The clinical use of cisplatin is highly restricted, because of its nephrotoxicity.In this study the protective effect of Nigella sativa (N. sativa) against cisplatin-induced nephrotoxicity was investigated in rats.
Materials and Methods: In the current study, the effects of the administration of aqueous-ethanolic extract of N. sativa (100 and 200 mg/kg, BW) and vitamin E (100 mg/kg, BW) against blood and urine biochemical alterations and kidney function in rats treated with cisplatin were investigated. Cisplatin was injected at a dose of 6 mg/kg, BW, on the sixth day of the experiment.
Results: The results indicated significant changes in serum urea and creatinine concentration, urine glucose concentration, and urine output in cisplatin group compared with control group. Serum urea and creatinine concentration in preventive and preventive+treatment vitamin E and preventive+treatment N. sativa (200 mg/kg, BW) groups and also serum creatinine concentration in preventive+treatment N. sativa (100 mg/kg, BW) group significantly decreased compared with cisplatin group. Urine glucose concentration in preventive and preventive+treatment N. sativa groups and urine output in preventive and preventive+treatment N. sativa (200 mg/kg, BW) groups significantly decreased compared with cisplatin group.Osmolarity excretion rate in preventive and preventive+treatment vitamin E and preventive N. sativa groups was significantly higher than control group.
Conclusions: The current study suggests that N. sativa extract and vitamin E in a dose- and time-dependent manner improved the serum and urine biochemical parameters and kidney function in cisplatin-induced nephrotoxicity in rats. However, it needs more investigations to determine the mechanism of N. sativa action on cisplatin-induced kidney toxicity.

Keywords

Main Subjects


Ahmad A, Husain A, Mujeeb M, Alam Khan S, Najmi AK, Siddique NA, Damanhouri ZA, Anwar F. 2013. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac J Trop Biomed, 3: 337-352.
Ali BH, Blunden G. 2003. Pharmacological and toxicological properties of Nigella sativa. Phytother Res, 17: 299-305.          
Alimohammadi S, Hobbenaghi R, Javanbakht J, Kheradmand D, Mortezaee R, Tavakoli M, Khadivar F, Akbari H. 2013. Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation. Diagn Pathol, 8: 137.      
Al-Naqeeb G, Maznah I, Al-Zubairi AS. 2009. Fatty acid profile, α-tocopherol content and total antioxidant activity of oil extracted from Nigella sativa seeds. Int J Pharmacol, 5: 244-250.
Antunes LMG, Darin JDC, Bianchi LMP. 2001. Effects of the antioxidants curcumin or selenium on cisplatin-induced nephrotoxicity and lipid peroxidation in rats. Pharmacol Rese, 43: 145–150.
Arany I, Megyesi JK, Kaneto H, Price PM, Safirstein RL. 2004. Cisplatin-induced cell death is EGFR/src/ERK signaling dependent in mouse proximal tubule cells. Am J Physiol Renal Physiol, 287: F543–F549.     
Ashraf SS, Rao MV, Kaneez FS, Qadri S, Al-Marzouqi AH, Chandranath IS, Adem A. 2011. Nigella sativa extract as a potent antioxidant for petrochemical-induced oxidative stress.J Chromatogr Sci, 49: 321-326.
Badary OA. 1999. Thymoquinone attenuates ifosfamide-induced Fanconi syndrome in rats and enhances its antitumor activity in mice. J Ethnopharmacol, 67: 135-42.         
Badary OA, Nagi MN, Al-Shabanah OA, Al-Sawaf HA, Al-Sohaibani MO, Al-Bekairi AM. 1997. Thymoquinone ameliorates the nephrotoxicity induced by cisplatin in rodents and potentiates its antitumor activity. Can J Physiol Pharmacol, 75: 1356-1361.         
Butt MS, Sultan MT. 2010. Nigella sativa: reduces the risk of various maladies. Crit Rev Food Sci Nutr, 50: 654-665.
Chehl N, Chipitsyna G, Gong Q, Yeo CJ, Arafat HA.2009. Anti-inflammatory effects of the Nigella sativa seed extract, thymoquinone, in pancreatic cancer cells.HBP (Oxford), 11: 373-381. 
Chirino YI, Pedraza-Chaverri J. 2009. Role of oxidative and nitrosative stress in cisplatin-induced nephrotoxicity. Exp Toxicol Pathol, 61: 223-242.
Ciarimboli G. 2014. Membrane Transporters as Mediators of Cisplatin Side Effects. Anticancer Res, 34: 547-550.     
Egawa Takata T, Endo H, Fujita M, Ueda Y, Miyatake T, Okuyama H, Yoshino K, Kamiura S, Enomoto T, Kimura T. 2010. Early reduction of glucose uptake after cisplatin treatment is a marker of cisplatin sensitivity in ovarian cancer. Cancer Sci, 101: 2171-1278.       
El Daly ES. 1996. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J Islamic Acad Sci , 9: 105-118.
Fallah Huseini H, Amini M, Mohtashami R, Ghamarchehre ME, Sadeqhi Z, Kianbakht S, Fallah Huseini A. 2013. Blood pressure lowering effect of Nigella sativa L. seed oil in healthy volunteers: a randomized, double-blind, placebo-controlled clinical trial. Phytother Res, 27: 1849-1853. 
Francescato HD, Coimbra TM, Costa RS, Bianchi Mde L. 2004. Protective effect of quercetin on the evolution of cisplatin-induced acute tubular necrosis. Kidney Blood Press Res, 27: 148-158.                       
Ikari A, Nagatani Y, Tsukimoto M, Harada H, Miwa M, Takagi K. 2005. Sodium-dependent glucose transporter reduces peroxynitrite and cell injury caused by cisplatin in renal tubular epithelial cells.Biochim Biophys Acta, 1717: 109-117.     
Ito Y, Arahata Y, Goto Y, Hirayama M, Nagamutsu M, Yasuda T, Yanagi T, Sobue G.1998. Cisplatin neurotoxicity presenting as reversible posterior leukoencephalopathy syndrome. Am J Neuroradiol, 19: 415.
Katzung BG. 2004. Basic and Clinical Pharmacology. pp. 906, NewYork: McGraw-Hill. 
Kawai Y, Nakao T, Kunimura N,Kohda Y, Gemba M. 2006. Relationship of intracellular calcium and oxygen radicals to Cisplatin-related renal cell injury. J PharmacolSci, 100: 65–72.
Khan A, Chen HC, Tania M, Zhang DZ. 2011.Anticancer Activities of Nigella sativa (Black Cumin). Afr J Tradit Complement Altern Med, 8: 226-232.
Kim SW, Lee JU, Nah MY, Kang DG, Ahn KY, Lee HS, Choi KC. 2001. Cisplatin decreases the abundance of aquaporin water channels in rat kidney. J Am Soc Nephrol,12: 875-882.
Kim YH, Kim YW, Oh YJ, Back N, Chung SA, Chung HG, Jeong TS, Choi MS, Lee KT. 2006. Protective effect of the ethanol extract of the roots of Brassica rapa on cisplatin-induced nephrotoxicity in LLC-PK1 cells and rats. Biol Pharm Bull, 29: 2436-2441.
Kim YK, Byun HS, Kim YH, Woo JS, Lee SH. 1995. Effect of cisplatin on renal function in rabbits:mechanism of reduced glucose reabsorption. Toxicol Appl Pharmacol, 130: 19-26.
Kishore BK, Krane CM, Di Iulio D, Menon AG, Cacini W. 2000. Expression of renal aquaporins 1, 2, and 3 in a rat model of cisplatin-induced polyuria. Kidney Int, 58: 701-711.
Kroning R, Lichtenstein AK, Nagami GT. 2000. Sulfur-containing amino acids decrease cisplatin cytotoxicity and uptake in renal tubule epithelial cell lines. Cancer Chemother Pharmacol, 45: 43–49.    
Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. 2010. Mechanisms of Cisplatin Nephrotoxicity.Toxins, 2: 2490-2518.
Morsi NM. 2000. Antimicrobial effect of crude extracts of Nigella sativa on multiple antibiotics-resistant bacteria. Acta Microbiol Pol. 49: 63-74.    
Naghizadeh B, Boroushaki MT, Vahdati Mashhadian N, Mansouri SMT. 2008. Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats. Iran Biomed J, 12: 93-100.
Nath KA, Norby SM. 2000. Reactive oxygen species and acute renal failure. Am J Med, 109: 665-678.  
Portilla D, Li S, Nagothu K, Megyesi J, Kaissling B, Schnackenberg L, Safirstein RL, Beger RD. 2006. Metabolomic study of cisplatin-induced nephrotoxicity. Kidney Int, 69: 2194-2204.   
Ramesh G, Reeves WB. 2004. Salicylate reduces cisplatin nephrotoxicity by inhibition of tumor necrosis factor-alpha. Kidney Int , 65: 490–499. 
Randhawa MA. 2008. Black seed, Nigella sativa, deserves more attention. J Ayub Med Coll Abbottabad, 20: 1-2.     
Razzaque MS. 2007. Cisplatin nephropathy: is cytotoxicity avoidable? Nephrol Dial Transplant, 22: 2112-2116.
Rooney S and Ryan MF. 2005. Effects of Alpha-hederin and Thymoquinone, constituents of Nigella sativa, on Human Cancer Cell Lines. Anticancer Res, 25: 2199-2204.       
Salama RHM, Abd-El-Hameed NA, Abd-El-Ghaffar SKH, Mohammed ZT, Ghandour NMA. 2011. Nephroprotective Effect of Nigella sativa and Matricaria chamomilla in Cisplatin Induced Renal Injury. Int J Clin Med, 2: 185-195.      
Salem ML. 2005. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int J Immunopharmacol, 5: 1749-1770.           
Shimeda Y, Hirotani Y, Akimoto Y, Shindou K, Ijiri Y, Nishihori T, Tanaka K. 2005. Protective Effects of Capsaicin against Cisplatin-Induced Nephrotoxicity in Rats. Biol Pharm Bull, 28: 1635-1638.
Tikoo K, Bhatt DK, Gaikwad AB, Sharma V, Kabra DG.2007.Differential effects of tannic acid on cisplatin induced nephrotoxicity in rats. FEBS Lett, 581: 2027-2035.     
Wong NL, Walker VR, Wong EF, Sutton RA.1993. Mechanism of polyuria after cisplatin therapy.Nephron, 65: 623-627.
Yaman I, Balikci E. 2010. Protective effects of Nigella sativa against gentamicin-induced nephrotoxicity in rats. Exp Toxicol Pathol, 62: 183-19           
Yao X, Panichpisal K, Kurtzman N, Nugent K. 2007. Cisplatin nephrotoxicity: a review. Am J Med Sci, 334: 115-124.