Effect of Nigella sativa fixed oil on ethanol toxicity in rats

Document Type : Original Article

Authors

1 Food Control Laboratory, Food and Drug Administration, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Phamacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 Pharmaceutical Research Center, Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4 Medical Toxicology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Phamacodynamy and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

6 Pharmaceutical Research Center, Department of Pharmacodynamy and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s):This study was planned to appraise the protective effect of Nigella sativa fixed oil (NSO) against subchronic ethanol induced toxicity in rats.
Materials and Methods: Studies were carried out on six groups of six animals each, including control (normal saline, gavage), ethanol (3 g/kg/day, gavage), NSO (0.125, 0.25 and 0.5 ml/Kg/day, IP) plus ethanol and NSO (0.5 ml/Kg/day, IP) groups. Treatments were continued for 4 weeks.
Results: According to data, treatment with NSO attenuated ethanol-induced increased levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), as well as histopathological changes in liver and kidney tissues. Moreover, NSO improved the level of serum liver enzymes (including alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and glutathione (GSH) content in liver and kidney tissues in ethanol-treated rats. Western blot analysis and quantitative real time RT-PCR showed that NSO treatment inhibited apoptosis stimulated by ethanol through decreasing the Bax/Bcl-2 ratio (both protein and mRNA levels), cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9 level in liver and kidney.
Conclusion: This study showed that NSO may have protective effects against hepatotoxicity and renal toxicity of ethanol by decreasing lipid peroxidation and inflammation and preventing apoptosis.

Keywords

References

1. Petroni NC, Cardoni AA. Alcohol content of liquid medicinals. Clin Toxicol 1979; 14:407-432.
2. Vogel C, Caraccio T, Mofenson H, Hart S. Alcohol intoxication in young children. Clin Toxicol 1995; 33:25-33.
3. Charness ME, Simon RP, Greenberg DA. Ethanol and the nervous system. N Engl J Med 1989; 321:442-454.
4. Diamond I, Messing RO. Neurologic effects of alcoholism. West J Med 1994; 161:279-287.
5. Adler RA. Clinically important effects of alcohol on endocrine function. J Clin Endocrinol Metab 1992; 74:957–960.
6. Lieber CS. Hepatic and metabolic effects of ethanol: pathogenesis and prevention. Ann Med 1994; 26:325–330.
7. Lieber CS. Medical disorders of alcoholism. N Engl J Med 1995; 333:1058–1065.
8. Yang HY, Lin HS, Chao JC, Chien YW, Peng HC, Chen JR. Effects of soy protein on alcoholic liver disease in rats undergoing ethanol withdrawal. J Nut Biochem 2012; 23:679-684.
9. Darwish HA, Abd Raboh NR, Mahdy A. Camel’s milk alleviates alcohol-induced liver injury in rats. Food Chem Toxicol 2012; 50 1377-1383.
10. Hossein Hosseinzadeh SP. Effect of thymoquinone and Nigella sativa seeds oil on lipid peroxidation level during global cerebral ischemia-reperfusion injury in rat hippocampus. Phytomedicine 2007; 14:621–627.
11. Jansen PM. Spices, Condiments and Medicinal Plants in Ethiopia, their Taxonomy and Agricultural Significance. Wageningen, The Netherlands: Centre for Agricultural Publishing and Documentation. 1981:194-205.
12. Chakravarty N. Inhibition of histamine release from mast cells by nigellone. Ann Allergy 1993; 70:237-242.
13. el-Dakhakhny M. Studies on the Egyptian Nigella sativa L. IV. Some pharmacological properties of the seeds' active principle in comparison to its dihydro compound and its polymer. Arzneimittelforschung 1965; 15:1227-1229.
 14. Mahfouz M, Abdel-Maguid R, El-Dakhakhny M. The effect of ‘‘nigellone therapy’’ on the histaminopexic power of the blood sera in asthmatic patients. Arzneimittelforschung 1965; 15:1230–1234.
15. El Tahir KE, Ashour M, Al-Harbi MM. The cardiovascular actions of the volatile oil of the black seed (Nigella sativa) in rats: elucidation of the mechanism of action. Gen Pharmacol 1993; 24: 1123-1131.
16. Al-Ghamdi M. The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa. J Ethnopharmacol 2001; 76:45-48.
17. Houghton PJ, Zarka R, de las Heras B, Hoult J. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med 1995; 61: 33-36.
18. Abdel-Fattah A-FM, Matsumoto K, Watanabe H. Antinociceptive effects of Nigella sativa oil and its major component, thymoquinone, in mice. Eur J Pharmacol 2000; 400: 89-97.
19. Al-Hader A, Aqel M, Hasan Z. Hypoglycemic effects of the volatile oil of Nigella sativa seeds. Pharmaceut Biol 1993; 31:96-100.
20. Topozada HH, Mazolum HA, El-Dakhakhny M. The antibacterial properties of Nigella sativa seeds, active principle with some clinical applications. J Egypt Med Assoc 1965; 48:187–202.
21. Hanafy MS, Hatem ME. Studies on the antimicrobial activity of Nigella sativa seed black cumin. J Ethnopharmacol 1991; 34:275–278.
22. Salomi N, Nair S, Jayawardhanan K, Varghese C, Panikkar L. Anti-tumor principles from Nigella sativa and saffron (Crocus sativus) on chemical carcinogenesis in mice. Nutr Cancer 1992; 16:67-72.
23. Hosseinzadeh H, Parvardeh S. Anticonvulsant effects of thymoquinone, the major constituent of Nigella sativa seeds, in mice. Phytomedicine 2004; 11:56-64.
24. Hosseinzadeh H, Parvardeh S, Nassiri-Asl M, Mansouri MT. Intracerebroventricular administration of thymoquinone, the major constituent of Nigella sativa seeds, suppresses epileptic seizures in rats. Med Sci Monit 2005; 11:BR106-BR110.
25. Hosseinzadeh H, Jaafari MR, Khoei AR, Rahmani M. Anti-ischemic effect of Nigella sativa L. seed in male rats. Iran J Pharm Res 2006; 5:53-58.
26. Worthen DR, Ghosheh OA, Crooks PA. The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. Anticancer Res 1998; 18:1527-1532.
27. Burits M, Bucar F. Antioxidant activity of Nigella sativa essential oil. Phytother Res 2000; 14:323-328.
28. Riaz M, Syed M, Chaudhary FM. Chemistry of the medicinal plants of the genus Nigella. Hamdard Medicus 1996; 39:40–45.
29. Ali BH, Blunden G. Pharmacological and Toxicological Properties of Nigella sativa. Phytother Res 2003; 17:299–305.
30. Mahfouz M, Abdel-Meguid R, El-Dakhakimy M. Effectiveness of ‘Nigella’ in asthma. Alexandria Med J 1960; 6: 543–547.
31. D’Antuono LF, Moretti A, Lovato A. Seed yield, yield components, oil content and essential oil content and composition of Nigella sativa L. and Nigella damascene L. Indust Crops Prod 2002; 15:59–69.
32. Niehaus WG Jr, Samuelsson B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968; 6:126–130.
33. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S transferase activities in rat lung and liver. Biochim Biophys Acta 1979; 582:67–78.
34. Jurczuk M, Brzóska MM, Moniuszko-Jakoniuk J, Gałazyn-Sidorczuk M, Kulikowska-Karpińska E. Antioxidant enzymes activity and lipid peroxidation in liver and kidney of rats exposed to cadmium and ethanol. Food Chem  Toxicol 2004; 42:429-438.
35. Scott RB, Reddy KS, Husain K, Schlorff EC, Rybak LP, Somani SM. Dose response of ethanol on antioxidant defense system of liver, lung, and kidney in rat. Pathophysiology 2000; 7:25-32.
36. Hoek JB, Pastorino JG. Ethanol, oxidative stress, and cytokine-induced liver cell injury. Alcohol 2002; 27:63-68.
37. Yoon SJ, Koh EJ, Kim CS, Jee OP, Kwak JH, Jeong WJ, et al. Agrimonia eupatoria protects against chronic ethanol-induced liver injury in rats. Food Chem Toxicol 2012; 50:2335-2341.
38. Arslan SO, Ethem Gelir TE, Armutcu F, Coskun O, Gurel A, Hale Sayan, et al. The protective effect of thymoquinone on ethanol-induced acute gastric damage in the rat. Nutr Res 2005; 25:673–680.
39.      El-Dakhakhny M, Barakat M, Abd El-Halim M, Aly SM. Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in rats. J Ethnopharmacol 2000; 72:299-304.
40. Lu ZM, Tao WY, Zou XL, Fu HZ, Ao ZH. Protective effects of mycelia of Antrodia camphorata and Armillariella tabescens in submerged culture against ethanol-induced hepatic toxicity in rats. J Ethnopharmacol 2007; 110:160-164.
 41. Esposito E, Cuzzocrea S. TNF-alpha as a therapeutic target in inflammatory diseases, ischemia-reperfusion injury and trauma. Curr Med Chem 2009; 16:3152–3167.
42. Shirpoor A, Minassian S, Salami S, Khadem-Ansari MH, Ghaderi-Pakdel F, Yeghiazaryan M. Vitamin E protects developing rat hippocampus and cerebellum against ethanol-induced oxidative stress and apoptosis. Food Chem 2009; 113:115-120.
43. El Daly E. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J Pharm Belg 1998; 53:87-93.
44. El-Dakhakhny M, Mady NI, Halim MA. Nigella sativa L. oil protects against induced hepatotoxicity and improves serum lipid profile in rats. Arzneimittelforschung 2000; 50:832-836.
45. Mansour MA. Protective effects of thymoquinone and desferrioxamine against hepatotoxicity of carbon tetrachloride in mice. Life Sci 2000; 66:2583-2591.
46. Helal GK. Thymoquinone supplementation ameliorates acute endotoxemia-induced liver dysfunction in rats. Pak J Pharm Sci 2010; 23:131-137.
47. Fadeel B, Orrenius S, Zhivotovsky B. Apoptosis in human disease: a new skin for the old ceremony? Biochem Biophys Res Commun 1999; 266:699-717.
48. Kumar S, Sitasawad SL. N-acetylcysteine prevents glucose/glucose oxidase-induced oxidative stress, mitochondrial damage and apoptosis in H9c2 cells. Life Sci 2009; 84:328-336.
49. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 35:495-516.
50. Frenzel A, Grespi F, Chmelewskij W, Villunger A. Bcl2 family proteins in carcinogenesis and the treatment of cancer. Apoptosis 2009; 14:584–596.
51. Scorrano L, Korsmeyer S. Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochem Biophys Res Commun 2003; 304:437–444.
52. Abd El-Ghany RM, Sharaf NM, Kassem LA, Mahran LG, Heikal OA. Thymoquinone triggers anti-apoptotic signaling targeting death ligand and apoptotic regulators in a model of hepatic ischemia reperfusion injury. Drug Discov Ther 2009; 3:296-306.
 
 
Iranian Journal of Basic Medical Sciences
Volume 17, Issue 12 - Serial Number 12
December 2014
Pages 1020-1031

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