Adriamycin-induced oxidative stress is prevented by mixed hydro-alcoholic extract of Nigella sativa and Curcuma longa in rat kidney

Document Type : Original Research Article


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

2 Neurocognitive Research Center and department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Department of Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Pathology, Qaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran

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

6 Department of Physiology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran


Objective: Inflammation and oxidative stress is considered to have a crucial role in induction of nephropathy. Curcuma longa (C. longa) and Nigella sativa (N. sativa) have anti-inflammatory and antioxidant effects. This study was designed to investigate the effect of mixed hydro-alcoholic extract of N.sativa and C. longa on the oxidative stress induced by Adriamycin (ADR) in rat kidney.
Material and Method: The animals were divided into 6 groups: control (CO), ADR, Adriamycin+ Vitamin C (ADR+VIT C), C. longa extract+ Adriamycin (C.LE+ADR), N. sativa extract+ Adriamycin (N.SE+ADR) and C. longa extract+ N. sativa extract + Adriamycin (N.S+C.L+ADR). ADR (5mg/kg) was injected intravenously, whereas VITC (100mg/kg) and extract of C. longa (1000mg/kg) and N. sativa (200mg/kg) were administrated orally. Finally, the renal tissue, urine and blood samples were collected and submitted to measure of redox markers, osmolarity and renal index.
Results: The renal content of total thiol and superoxide dismutase (SOD) activity significantly decreased and Malondialdehyde (MDA) concentration increased in Adriamycin group compared to control group. The renal content of total thiol and SOD activity significantly enhanced and MDA concentration reduced in treated-mixed extract of C. longa and N. sativa along with ADR group compared to ADR group. The mixed extract did not restore increased renal index percentage induced by ADR. There also was no significant difference in urine and serum osmolarity between the groups.
Conclusion: hydro-alcoholic extracts of N.sativa and C.longa led to an improvement in ADR-induced oxidative stress and mixed administration of the extracts enhanced the aforementioned therapeutic effect.


Main Subjects

Ahmad A, Husain A, Mujeeb M, Khan SA, 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.
Akram M, Uddin S, Ahmed A, Usmanghani K, Hannan A, Mohiuddin E, Asif M. 2001. Curcuma longa and curcumin: a review article. Rom J Biol, 55: 65–70.
Babu PS, Srinivasan K. 1997. Hypolipidemic action of curcumin, the active principle of turmeric (Curcuma longa) in streptozotocin induced diabetic rats. Mol Cell Biochem, 166: 169-175.
Cizmarikova M, Podracka L, Klimcakov AL, Habalova V, Boor A, Mojzis J, Mirossay L. 2015. MDR1 polymorphisms and idiopathic nephrotic syndrome in Slovak children: preliminary results. Med Sci Monit, 21: 59-68.
Cohly H, Taylor A, Angel MF, Salahudeen AK. 1998. Effect of turmeric, turmerin and curcumin on H2O2-induced renal epithelial (LLC-PK1) cell injury. Free Radic Biol Med, 24: 49-54.
Antunes Lm, D'arc J, Bianchi Md. 2000. Protective effects of vitamin C against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: a dose-dependent study. Pharmacological Research, 41: 405-411.
Hosseinzadeh H, Parvardeh S, Asl MN, Sadeghnia HR, Ziaee T. 2007. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine, 14: 621-627.
Jadhav VB, Thakare VN, Suralkar AA, Naik SR. 2013. Ameliorative effect of Luffa acutangula Roxb. on doxorubicin induced cardiac and oxidative stress in mice. Indian J Exp Biol, 51: 149-156.
Janero DR. 1990. Malondialdehyde and thiobarbituric acid-reactivity as diagnostic indices of lipid peroxidation and peroxidative tissue injury. Free Radic Biol Med, 9: 515-540.
Khan N, Sultana S. 2005. Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa. Eur J Cancer Prev, 14: 159-168.
Khazdair MR. 2015. The Protective Effects of Nigella sativa and Its Constituents on Induced Neurotoxicity. J Toxicol, 2015, 1-7.
Khorsandi L, Orazizadeh M. 2008. Protective effect of Curcuma longa extract on acetaminophen induced nephrotoxicity in mice. DARU, 16: 155-159.
Lee VW, Harris DC. 2011. Adriamycin nephropathy: a model of focal segmental glomerulosclerosis. Nephrology (Carlton), 16: 30-38.
Madesh M, Balasubramanian KA. 1998. Microtiter plate assay for superoxide dismutase using MTT reduction by superoxide. Indian J Biochem Biophys, 35: 184-188.
Medina-Navarro R, Corona-Candelas I, Barajas-Gonzalez S, Diaz-Flores M, Duran-Reyes G. 2014. Albumin antioxidant response to stress in diabetic nephropathy progression. PLoS One, 9: e106490.
Nakakura H, Ashida A, Hirano K, Tamai H. 2004. Oxidative stress in a rat model of nephrosis can be quantified by electron spin resonance. Pediatr Nephrol, 19: 266-270.
Omran OM. 2014. Effects of thymoquinone on STZ-induced diabetic nephropathy: an immunohistochemical study. Ultrastruct Pathol, 38: 26-33.
Quiles JL, Huertas JR, Battino M, Mataix, J, Ramirez-Tortosa MC. 2002. Antioxidant nutrients and adriamycin toxicity. Toxicology, 180: 79-95.
Rybi-Szuminska A, Wasilewska A, Michaluk-Skutnik J, Osipiuk-Remza B, Filonowicz R, Zajac M. 2014. Are oxidized low-density lipoprotein and C-reactive protein markers of atherosclerosis in nephrotic children? Ir J Med Sci, 184:775-780.
Salama SM, Abdulla MA, Alrashdi AS, Ismail S, Alkiyumi SS, Golbabapour S. 2013. Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats. BMC Complement Altern Med, 13: 56.
Saleem U, Ahmad B, Rehman K, Mahmood S, Alam M, Erum A. 2012. Nephro-protective effect of vitamin C and Nigella sativa oil on gentamicin associated oxidative stress in rabbits. Pak J Pharm Sci, 25: 727-730.
Sarhan M, El Serougy H, Hussein AM, El-Dosoky M, Sobh MA, Fouad SA, Sobh M, Elhusseini F. 2014. Impact of bone-marrow-derived mesenchymal stem cells on adriamycin-induced chronic nephropathy. Can J Physiol Pharmacol, 92: 733-743.
Sharma JB, Sharma A, Bahadur A, Vimala N, Satyam A, Mittal S. 2006. Oxidative stress markers and antioxidant levels in normal pregnancy and pre-eclampsia. Int J Gynaecol Obstet, 94: 23-27.
Sharma OP. 1976. Antioxidant activity of curcumin and related compounds. Biochem Pharmacol, 25: 1811-1812.
Staniek K, Gille L. 2010. Is thymoquinone an antioxidant? BMC Pharmacol, 10, A9.
Venkatesan N. 1998. Curcumin attenuation of acute adriamycin myocardial toxicity in rats. Br J Pharmacol, 124: 425-427.
Venkatesan N, Punithavathi D, Arumugam V. 2000. Curcumin prevents adriamycin oxidative stress in rats. Br J Pharmacol, 129: 231-234.
Zima T, Tesar V, Crkovska J, Stejskalova A, Platenik J, Teminova J, Nemecek K, Janebova M, Stipek S. 1998. ICRF-187 (dexrazoxan) protects from adriamycin-induced nephrotic syndrome in rats. Nephrol Dial Transplant, 13: 1975-1979.