@2024 Afarand., IRAN
ISSN: 2252-0805 The Horizon of Medical Sciences 2016;22(1):13-20
ISSN: 2252-0805 The Horizon of Medical Sciences 2016;22(1):13-20
Effect of Hydroalcholic Extract of Nigella sativa on Doxorubicin-Induced Functional Damage of Kidney in Rats
ARTICLE INFO
Article Type
Original ResearchAuthors
Mohebbati R. (1)Abbsnezhad A. (2)
Khajavi Rad A. (*)
Mousavi S.M. (1)
Haghshenas M. (1)
(*) Physiology Department, Medicine Faculty, Mashhad University of Medical Sciences, Mashhad, Iran
(1) Physiology Department, Medicine Faculty, Mashhad University of Medical Sciences, Mashhad, Iran
(2) Basic Sciences Department, Medicine Faculty, Gonabad University of Medical Sciences, Gonabad, Iran
Correspondence
Address: Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Azadi Square, Mashhad, Iran. Postal Code: 917794-8564Phone: +985138828565
Fax: +985138828564
khajavirada@mums.ac.ir
Article History
Received: May 30, 2015Accepted: October 31, 2015
ePublished: December 15, 2015
ABSTRACT
Aims
Doxorubicin is an important anti-cancer drug which can cause renal toxicity. Nigella sativa has anti-inflammatory and antioxidant effects. The aim of this study was to determine the effects of hydroalcoholic extract of Nigella sativa on doxorubicin-induced functional damage of kidney in rats.
Materials & Methods This experimental study was implemented, using 32 male Wistar rats which were divided randomly into 4 groups; control, doxorubicin (5mg/kg), Nigella sativa extract (200mg/kg) and Nigella sativa plus doxorubicin. The groups were treated for 5 consecutive weeks and on days 0, 6, 10, 14, 21, 28, 35; the 24-hour urine samples and serum were collected to measure the levels of serum and urine glucose, serum urea, urea clearance and Glomerular Filtration Rate. Statistical analyses were made using one-way ANOVA followed by the Tukey’s test and paired T test.
Findings The mean of serum urea on day 10 in doxorubicin group was significantly increased compared to the pre-injection state. The mean of urine glucose on day 28 in Nigella sativa plus doxorubicin group was significantly decreased compared to doxorubicin group. The means of GFR on days 21 and 35 in doxorubicin group were significantly decreased compared to control day. The means of GFR on days 21, 28, 35 in Nigella sativa plus doxorubicin group were significantly increased compared to doxorubicin group. The means of glucose on days 21 and 28 in doxorubicin group were significantly decreased compared to control day.
Conclusion The hydroalcoholic extract of Nigella sativa reduces the doxorubicin-induced functional damage of kidney in rats and helps improve the Glomerular Filtration Rate rate and decreases the glucosuria.
Materials & Methods This experimental study was implemented, using 32 male Wistar rats which were divided randomly into 4 groups; control, doxorubicin (5mg/kg), Nigella sativa extract (200mg/kg) and Nigella sativa plus doxorubicin. The groups were treated for 5 consecutive weeks and on days 0, 6, 10, 14, 21, 28, 35; the 24-hour urine samples and serum were collected to measure the levels of serum and urine glucose, serum urea, urea clearance and Glomerular Filtration Rate. Statistical analyses were made using one-way ANOVA followed by the Tukey’s test and paired T test.
Findings The mean of serum urea on day 10 in doxorubicin group was significantly increased compared to the pre-injection state. The mean of urine glucose on day 28 in Nigella sativa plus doxorubicin group was significantly decreased compared to doxorubicin group. The means of GFR on days 21 and 35 in doxorubicin group were significantly decreased compared to control day. The means of GFR on days 21, 28, 35 in Nigella sativa plus doxorubicin group were significantly increased compared to doxorubicin group. The means of glucose on days 21 and 28 in doxorubicin group were significantly decreased compared to control day.
Conclusion The hydroalcoholic extract of Nigella sativa reduces the doxorubicin-induced functional damage of kidney in rats and helps improve the Glomerular Filtration Rate rate and decreases the glucosuria.
Keywords:
Nigella sativa ,
Renal Insufficiency ,
Doxorubicin,
Glomerular Filtration Rate ,
Glucosuria,
CITATION LINKS
[1]Lee VW, Harris DC. Adriamycin nephropathy: A model of focal segmental glomerulosclerosis. Nephrol. 2011;16(1):30-8.
[2]Balakumar P, Chakkarwar VA, Kumar V, Jain A, Reddy J, Singh M. Experimental models for nephropathy. J Renin Angiotensin Aldosterone Syst. 2008;9(4):189-95.
[3]Jeansson M, Björck K, Tenstad O, Haraldsson B. Adriamycin alters glomerular endothelium to induce proteinuria. J Am Soc Nephrol. 2009;20(1):114-22.
[4]Venkatesan N, Punithavathi D, Arumugam V. Curcumin prevents adriamycin nephrotoxicity in rats. Br J Pharmacol. 2000;129(2):231-4.
[5]Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res. 2003;17(4):299-305.
[6]Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol. 2005;5(13-14):1749-70.
[7]Boskabady MH, Shirmohammadi B, Jandaghi P, Kiani S. Possible mechanism(s) for relaxant effect of aqueous and macerated extracts from Nigella sativa on tracheal chains of guinea pig. BMC Pharmacol. 2004;4:3.
[8]Randhawa MA. Black seed, Nigella sativa, deserves more attention. J Ayub Med Coll Abbottabad. 2008;20(2):1-2.
[9]Gilani A-uH, Jabeen Q, Allah Khan MA. A review of medicinal uses and pharmacological activities of Nigella sativa. Pak J Biol Sci. 2004;7(4):441-51.
[10]Uz E, Bayrak O, Kaya A, Bayrak R, Uz B, Turgut FH, et al. Nigella sativa oil for prevention of chronic cyclosporine nephrotoxicity: An experimental model. Am J Nephrol. 2008;28(3):517-22.
[11]Yaman I, Balikci E. Protective effects of Nigella sativa against gentamicin-induced nephrotoxicity in rats. Exp Toxicol Pathol. 2010;62(2):183-90.
[12]Burtis C, Ashwood E, Bruns D. Tietz textbook of clinical chemistry and molecular diagnostics. New York: Elsevier Health Sciences; 2015.
[13]Zima T, Tesar V, Crkovska J, Stejskalová A, Platenik J, Teminova J, et al. ICRF-187 (dexrazoxan) protects from adriamycin-induced nephrotic syndrome in rats. Nephrol Dial Transplant. 1998;13(8):1975-9.
[14]Chromý V, Rozkošná K, Sedlak P. Determination of serum creatinine by Jaffe method and how to calibrate to eliminate matrix interference problems. Clin Chem Lab Med. 2008;46(8):1127-33.
[15]Montilla P, Tunez I, Munoz MC, Lopez A, Soria JV. Hyperlipidemic nephropathy induced by adriamycin: effect of melatonin administration. Nephron. 1997;76(3):345-50.
[16]Di Marco A, Arcamone F, Zunino F. Daunomycin (daunorubicin) and adriamycin and structural analogues: biological activity and mechanism of action. In: Corcoran JW, Hahn FE. Mechanism of Action of Antimicrobial and Antitumor Agents Antibiotics. New York: Springer Science & Business Media; 2012.
[17]Sarhan M, El Serougy H, Hussein AM, El-Dosoky M, Sobh MA, Fouad SA, et al. Impact of bone-marrow-derived mesenchymal stem cells on adriamycin-induced chronic nephropathy. Can J Physiol Pharmacol. 2014;92(9):733-43.
[18]Liang Cl, Wu Jb, Lai J, Ye S, Lin J, Ouyang H, et al. Protection effect of Zhen-Wu-Tang on Adriamycin-Induced Nephrotic syndrome via inhibiting oxidative lesions and inflammation damage. Evid Based Complement Altern Med. 2014;2014:1-11.
[19]Zhu C, Xuan X, Che R, Ding G, Zhao M, Bai M, et al. Dysfunction of the PGC-1alpha-mitochondria axis confers adriamycin-induced podocyte injury. Am J Physiol Renal Physiol. 2014;306(12):1410-7.
[20]Wang Z, Liu JT, Sun WS, Li RP, Wang Y. Effect of Qufeng Tongluo Recipe on expression of desmin and CD2AP proteins in adriamycin-induced nephropathy rats: An experimental research. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014;34(2):203-8.
[21]Wei M, Sun W, He W, Ni L, Cai X, Cheng Z, et al. Qiguiyishen decoction reduced the accumulation of extracellular matrix in the kidneys of rats with adriamycin-induced nephropathy. J Tradit Chin Med. 2014;34(3):351-6.
[22]Elsherbiny NM, El-Sherbiny M. Thymoquinone attenuates Doxorubicin-induced nephrotoxicity in rats: Role of Nrf2 and NOX4. Chem Biol Interact. 2014;223C:102-8.
[23]Hommel E, Mathiesen ER, Aukland K, Parving HH. Pathophysiological aspects of edema formation in diabetic nephropathy. Kidney Int. 1990;38(6):1187-92.
[24]You H, Lu Y, Gui D, Peng A, Chen J, Gu Y. Aqueous extract of Astragali Radix ameliorates proteinuria in adriamycin nephropathy rats through inhibition of oxidative stress and endothelial nitric oxide synthase. J Ethnopharmacol. 2011;134(1):176-82
[25]Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, et al. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res. 1999;59(3):597-601.
[26]Franco R, Gut A, Ferrari-Spadotto A, Georgette J, Gavras I, Gavras H. Pressor mechanisms in adriamycin-induced nephropathy with hypertension in rats. Hypertens. 1994;23(1):246-9.
[27]Koul A, Shubrant S, Gupta P. Phytomodulatory potential of lycopene from Lycopersicum esculentum against doxorubicin induced nephrotoxicity. Indian J Exp Biol. 2013;51(8):635-45.
[28]Jadhav VB, Thakare VN, Suralkar AA, Naik SR. Ameliorative effect of Luffa acutangula Roxb. on doxorubicin induced cardiac and nephrotoxicity in mice. Indian J Exp Biol. 2013;51(2):149-56.
[2]Balakumar P, Chakkarwar VA, Kumar V, Jain A, Reddy J, Singh M. Experimental models for nephropathy. J Renin Angiotensin Aldosterone Syst. 2008;9(4):189-95.
[3]Jeansson M, Björck K, Tenstad O, Haraldsson B. Adriamycin alters glomerular endothelium to induce proteinuria. J Am Soc Nephrol. 2009;20(1):114-22.
[4]Venkatesan N, Punithavathi D, Arumugam V. Curcumin prevents adriamycin nephrotoxicity in rats. Br J Pharmacol. 2000;129(2):231-4.
[5]Ali BH, Blunden G. Pharmacological and toxicological properties of Nigella sativa. Phytother Res. 2003;17(4):299-305.
[6]Salem ML. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol. 2005;5(13-14):1749-70.
[7]Boskabady MH, Shirmohammadi B, Jandaghi P, Kiani S. Possible mechanism(s) for relaxant effect of aqueous and macerated extracts from Nigella sativa on tracheal chains of guinea pig. BMC Pharmacol. 2004;4:3.
[8]Randhawa MA. Black seed, Nigella sativa, deserves more attention. J Ayub Med Coll Abbottabad. 2008;20(2):1-2.
[9]Gilani A-uH, Jabeen Q, Allah Khan MA. A review of medicinal uses and pharmacological activities of Nigella sativa. Pak J Biol Sci. 2004;7(4):441-51.
[10]Uz E, Bayrak O, Kaya A, Bayrak R, Uz B, Turgut FH, et al. Nigella sativa oil for prevention of chronic cyclosporine nephrotoxicity: An experimental model. Am J Nephrol. 2008;28(3):517-22.
[11]Yaman I, Balikci E. Protective effects of Nigella sativa against gentamicin-induced nephrotoxicity in rats. Exp Toxicol Pathol. 2010;62(2):183-90.
[12]Burtis C, Ashwood E, Bruns D. Tietz textbook of clinical chemistry and molecular diagnostics. New York: Elsevier Health Sciences; 2015.
[13]Zima T, Tesar V, Crkovska J, Stejskalová A, Platenik J, Teminova J, et al. ICRF-187 (dexrazoxan) protects from adriamycin-induced nephrotic syndrome in rats. Nephrol Dial Transplant. 1998;13(8):1975-9.
[14]Chromý V, Rozkošná K, Sedlak P. Determination of serum creatinine by Jaffe method and how to calibrate to eliminate matrix interference problems. Clin Chem Lab Med. 2008;46(8):1127-33.
[15]Montilla P, Tunez I, Munoz MC, Lopez A, Soria JV. Hyperlipidemic nephropathy induced by adriamycin: effect of melatonin administration. Nephron. 1997;76(3):345-50.
[16]Di Marco A, Arcamone F, Zunino F. Daunomycin (daunorubicin) and adriamycin and structural analogues: biological activity and mechanism of action. In: Corcoran JW, Hahn FE. Mechanism of Action of Antimicrobial and Antitumor Agents Antibiotics. New York: Springer Science & Business Media; 2012.
[17]Sarhan M, El Serougy H, Hussein AM, El-Dosoky M, Sobh MA, Fouad SA, et al. Impact of bone-marrow-derived mesenchymal stem cells on adriamycin-induced chronic nephropathy. Can J Physiol Pharmacol. 2014;92(9):733-43.
[18]Liang Cl, Wu Jb, Lai J, Ye S, Lin J, Ouyang H, et al. Protection effect of Zhen-Wu-Tang on Adriamycin-Induced Nephrotic syndrome via inhibiting oxidative lesions and inflammation damage. Evid Based Complement Altern Med. 2014;2014:1-11.
[19]Zhu C, Xuan X, Che R, Ding G, Zhao M, Bai M, et al. Dysfunction of the PGC-1alpha-mitochondria axis confers adriamycin-induced podocyte injury. Am J Physiol Renal Physiol. 2014;306(12):1410-7.
[20]Wang Z, Liu JT, Sun WS, Li RP, Wang Y. Effect of Qufeng Tongluo Recipe on expression of desmin and CD2AP proteins in adriamycin-induced nephropathy rats: An experimental research. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014;34(2):203-8.
[21]Wei M, Sun W, He W, Ni L, Cai X, Cheng Z, et al. Qiguiyishen decoction reduced the accumulation of extracellular matrix in the kidneys of rats with adriamycin-induced nephropathy. J Tradit Chin Med. 2014;34(3):351-6.
[22]Elsherbiny NM, El-Sherbiny M. Thymoquinone attenuates Doxorubicin-induced nephrotoxicity in rats: Role of Nrf2 and NOX4. Chem Biol Interact. 2014;223C:102-8.
[23]Hommel E, Mathiesen ER, Aukland K, Parving HH. Pathophysiological aspects of edema formation in diabetic nephropathy. Kidney Int. 1990;38(6):1187-92.
[24]You H, Lu Y, Gui D, Peng A, Chen J, Gu Y. Aqueous extract of Astragali Radix ameliorates proteinuria in adriamycin nephropathy rats through inhibition of oxidative stress and endothelial nitric oxide synthase. J Ethnopharmacol. 2011;134(1):176-82
[25]Kawamori T, Lubet R, Steele VE, Kelloff GJ, Kaskey RB, Rao CV, et al. Chemopreventive effect of curcumin, a naturally occurring anti-inflammatory agent, during the promotion/progression stages of colon cancer. Cancer Res. 1999;59(3):597-601.
[26]Franco R, Gut A, Ferrari-Spadotto A, Georgette J, Gavras I, Gavras H. Pressor mechanisms in adriamycin-induced nephropathy with hypertension in rats. Hypertens. 1994;23(1):246-9.
[27]Koul A, Shubrant S, Gupta P. Phytomodulatory potential of lycopene from Lycopersicum esculentum against doxorubicin induced nephrotoxicity. Indian J Exp Biol. 2013;51(8):635-45.
[28]Jadhav VB, Thakare VN, Suralkar AA, Naik SR. Ameliorative effect of Luffa acutangula Roxb. on doxorubicin induced cardiac and nephrotoxicity in mice. Indian J Exp Biol. 2013;51(2):149-56.