Crocin Restores Hypotensive Effect of Subchronic Administration of Diazinon in Rats

Document Type: Original Article

Authors

1 School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

2 2Pharmaceutical Research Center, Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

3 3Department of Medicinal chemistry and Dept. of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

4 4Pharmaceutical Research Center, Department of Pharmacology, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Objective(s): In this study, the effects of crocin against subchronic toxicity of diazinon (DZN) on systolic blood pressure (SBP) and heart rate (HR) were evaluated in rats.
Materials and Methods: Rats were equally divided into 7 groups; control (corn oil), DZN (15 mg/kg), crocin (each group received 12.5, 25 or 50 mg/kg crocin plus DZN), vitamin E (200 IU/kg plus DZN) and crocin (50 mg/kg) treated groups.  Rats were given DZN via gavage once a day for 4 weeks. Vitamin E (three times per week) and crocin (once a day) were intraperitoneally injected to rats for 4 weeks. Plasma cholinesterase activity (Elman method), malondealdehyde (MDA) levels in the aortic tissue (Thiobarbituric acid reactive substances or TBARS method); SBP and HR (tail cuff method) were evaluated at the end of 4th week.
Results: A significant decrease in cholinesterase activity was observed in DZN group (P< 0.001). Crocin did not show any effects on cholinesterase activity. DZN increased MDA levels in aortic tissue (P< 0.001) in comparison with control group. Crocin and vitamin E plus DZN decreased MDA elevation induced by DZN in aortic tissue. DZN significantly reduced SBP (P< 0.01) and increased HR (P< 0.001) in comparison with control. Concurrent administration of crocin and DZN, improved the reduction of SBP and the elevation of HR induced by DZN in rat. Crocin alone did not have any effect on SBP and HR.
Conclusion: This study showed that concurrent administration of crocin and DZN could restore the effects of subchronic DZN administration on SBP and HR in rats.

Keywords


1. Liu L, Zhou S, Yang X, Wu S, Chen G. Paraoxon attenuates vascular smooth muscle contraction through inhibiting Ca2+ influx in the rabbit thoracic aorta. J Biomed  Biotechnol 2010; 2010:40-48.

2. Shadnia S, Abdollahi M, Sasanian G. Effects of N-acetyl-cysteine and alpha-tocopherol on diazinon toxicity. Toxicol Mech Methods 2007; 17:109-115.

3.  Zuin VG, Vilegas  JHY. Pesticide residues in medicinal plants and phytomedicines. Phytother Res 2000; 14:73-88.

4. Kalender S, Ogutcu A, Uzunhisarcikli M, Açikgoz F, Durak D, Ulusoy Y, et al. Diazinon-induced hepatotoxicity and protective effect of vitamin E on some biochemical indices and ultrastructural changes. Toxicology 2005; 211:197-206.

5. Handy RD, Abd-El Samei HA, Bayomy MFF, Mahran AM, Abdeen AM, El-Elaimy EA. Chronic diazinon exposure: Pathologies of spleen, thymus, blood cells, and lymph nodes are modulated by dietary protein or lipid in the mouse. Toxicology 2002; 172:13-34.

6. Ogutcu A, Uzunhisarcikli M, Kalender S, Durak D, Bayrakdar F, Kalender Y. The effects of organophosphate insecticide diazinon on malondialdehyde levels and myocardial cells in rat heart tissue and protective role of vitamin E. Pest Biochem  Physiol 2006; 86:93-98.

7.  Fernández J.  Anticancer properties of saffron, Crocus sativus Linn. Adv Phytomed 2006; 2:313-330.

8.  Konoshima T, Takasaki M, Tokuda H, Morimoto S, Tanaka H, Kawata E, et al. Crocin and crocetin derivatives inhibit skin tumour promotion in mice. Phytother Res 1998; 12:400-444.

9. Assimopoulou AN, Sinakos Z, Papageorgiou VP. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother Res 2005; 19:997-1000.

10. Hosseinzadeh H, Sadeghnia HR. Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharm Sci 2005a; 8:394-399.

11. Hosseinzadeh H, Sadeghnia HR, Ziaee T, Danaee A. Protective effect of aqueous saffron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J Pharm Pharm Sci 2005b; 8:387-393.

12.  Hosseinzadeh H, Shamsaie F, Mehri S. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituent, crocin and safranal. Pharmacogn Mag 2009; 5:419-424.

13. Abe K, Saito H. Effects of saffron extract and its constituent crocin on learning behaviour and long-term potentiation. Phytother Res 2000; 14:149-152.

14. Soeda S, Ochiai T, Shimeno H, Saito H, Abe K, Tanaka H, et al. Pharmacological activities of crocin in saffron. J Nat Med 2007; 61:102-111.

15. Hosseinzadeh H, Ziaei T. Effects of Crocus sativus stigma extract and its constituents, crocin and safranal, on intact memory and scopolamine-induced learning deficits in rats performing the Morris water maze task. J Med Plants 2006; 5:40-50.

16. Shen XC, Qian ZY. Effects of crocetin on antioxidant enzymatic activities in cardiac hypertrophy induced by norepinephrine in rats. Pharmazie 2006; 61:348-352.

17.  Akimov GA, Kolesnichenko IP. Morphological changes in the central nervous system after acute oral poisoning with chlorophos. Arkh Patol 1985; 47:44-51.

18. Antov G, Kazakova B, Popov T. Morphological and biochemical changes in the connective tissue in chronic chloroacetophone poisoning. Probl Khig 1984; 9:59–65.

19. Zlateva M, Belcheva L, Yurukova J. Arterial lesions in chronic intoxication with pesticides. I. Histological and enzymohistochemical studies of the aorta in rats treated with organophosphorus pesticides. Mediko-Biologichni Problemi 1982; 10:96-104.

20. Hadizadeh F, Mohajeri S, Seifi M. Extraction and purification of crocin from saffron stigmas employing a simple and efficient crystallization method. Pak J Biol Sci  2010; 13:691-8.

21. Rezg R, Mornagui B, El-Fazaa S, Gharbi N. Biochemical evaluation of hepatic damage in subchronic exposure to malathion in rats: effect on superoxide dismutase and catalase activities using native PAGE. C R Biol 2008; 331:655-662.

22. Hosseinzadeh H, Parvardeh S, Nassiri Asl M, Sadeghnia H, Ziaee T. 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.

23. Fernandez J, Perez-Alvarez JA, Fernandez-lopez JA. Thiobarbituric acid test for monitoring lipid oxidation in meat. Food Chem 1997; 99:345–353.

24. Lorenz JN. A practical guide to evaluating cardiovascular, renal, and pulmonary function in mice. Am J Physiol Regul Integr Comp Physiol 2002; 282:R1565-582.

25. Hariri AT, Moallem SA, Mahmoudi M, Hosseinzadeh H. The effect of crocin and safranal, constituents of saffron, against subacute effect of diazinon on hematological and genotoxicity indices in rats. Phytomedicine  2011; 18:499-504.

26. Calore EE, Perez NM, Herman MM. Morphometric studies of cardiac miocytes of rats chronically treated with an organophosphate. Ecotoxicol Environ Saf 2007; 66:447-450.

27. ‍‍Cetin N, ‍‍‍Cetin E, Eraslan G, Bilgili A. Chlorpyrifos induces cardiac dysfunction in rabbits. Res Vet Sci 2007; 82:405-408.

28. Hariri AT, Moallem SA, Mahmoudi M, Memar B, Hosseinzadeh H. Sub-acute effects of diazinon on biochemical indices and specific biomarkers in rats: Protective effects of crocin and safranal. Food Chem Toxicology 2010; 48:2803-2808.

29. Yavuz T, Delibas N, Yildirim B, Altuntas I, Candir O, Cora A, et al. Vascular wall damage in rats induced by organophosphorus insecticide methidathion. Toxicol Lett 2005; 155:59-64.

30.  Kojima T, Tsuda S, Shirasu Y.  Inhibitory effect of fenthion and diazinon on the contraction of rat aorta, and its contribution to lethality. J Vet Med Sci/ JPN Soc Vet Sci 1993; 55:383-385.

31. Costa LG, Schwab BW, Murphy SD. Tolerance to anticholinesterase compounds in mammals. Toxicology 1982; 25:79-97.

32. Alp H, Aytekin I, Atakisi O, Hatipoglu NK, Basara, K, Ogun M, et al. The effects of caffeic acid phenethyl ester and ellagic acid on the levels of malondialdehyde, reduced glutathione and nitric oxide in the lung, liver and kidney tissue in acute diazinon toxicity in rats. J Animal Vet Adv 2011; 10:1488-1494.

33. Joukar S, Najafipour H, Khaksari M, Sepehri G, Shahrokhi N, Dabiri S, et al. The effect of saffron consumption on biochemical and histopathological heart indices of rats with myocardial infarction. Cardiovasc Toxicol 2010; 10:66-71.

34. Goyal  S, Arora S, Sharma A, Joshi S, Ray R, Bhatia J, et al. Preventive effect of crocin of Crocus sativus on hemodynamic, biochemical, histopathological and ultrastuctural alterations in isoproterenol-induced cardiotoxicity in rats. Phytomedicine 2010; 17:227-232.

35. Imenshahidi M, Hosseinzadeh H, Javadpour Y. Hypotensive effect of aqueous saffron extract (Crocus sativus L.) and its constituents, safranal and crocin, in normotensive and hypertensive rats. Phytother Res 2010; 24:990-994.

36. Boskabady MH, Shafei MN, Shakiba A, Sang Sefidi H. Effect of aqueous-ethanol extract from Crocus sativus (saffron) on guinea-pig isolated heart. Phytother Res 2008; 22:330-334.

37. Nemati H, Boskabady MH, Ahmadzadeh vostakolaei H. Stimulatory effect of Crocus sativus (saffron) on β2-adrenoreceptors of guinea pig tracheal chains. Phytomedicine 2008; 15:1038-1045.