DOI QR코드

DOI QR Code

Effect of Crocus sativus L. stigma (saffron) against subacute effect of diazinon: histopathological, hematological, biochemical and genotoxicity evaluations in rats

  • Hariri, Alireza Timcheh ;
  • Moallem, Seyed Adel ;
  • Mahmoudi, Mahmoud ;
  • Memar, Bahram ;
  • Razavi, Bibi Marjan ;
  • Hosseinzadeh, Hossein
  • Received : 2017.05.10
  • Accepted : 2018.03.30
  • Published : 2018.06.30

Abstract

Objective: In this study, the effects of saffron stigma against subacute diazinon (DZN) toxicity on enzymes levels, biochemical, hematological, histopathological and genotoxicity indices were studied in rats. Methods: Vitamin E (200 IU/kg) and the aqueous extract of saffron (50, 100 and 200 mg/kg) were injected intraperitoneally three times per week alone or with DZN (20 mg/kg/day, orally) for 4 weeks. The hematological and biochemical parameters were evaluated at the end of 4 weeks. Results: Reticulocytes counts, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), creatine phosphokinase, CPK-MB, gama glutamyl transferase (GGT), uric acid and micronucleus indices were increased significantly but total protein and RBC cholinesterase activity were decreased in the DZN-treated group. Saffron prevented the effect of DZN on GGT (50 mg/kg), LDH, CPK and CPK-MB (100 and 200 mg/kg) levels. An increased uric acid and reduced protein levels by DZN were prevented by vitamin E and some doses of saffron. A significant reduction was observed in platelets, RBC, hemoglobin and hematocrit indices in the DZN group. Saffron and vitamin E prevented this reduction. Vitamin E and saffron did not reduce the effect of DZN on RBC cholinesterase activity. The extract and vitamin E could not prevent DZN genotoxicity in the micronucleus assay. Other biochemical parameters and pathological evaluation did not show any abnormality in tissues of all groups. Conclusion: This study shows that vitamin E and saffron reduce DZN induced hematological and biochemical toxicity. However, they do not prevent the genotoxicity induced by DZN.

Keywords

Diazinon;Organophosphorus pesticides;Saffron;Crocus sativus;hematological and biochemical indices;genotoxicity;micronucleus assay

References

  1. Bosak A. Organophosphorus compounds: classification and enzyme reactions. Arh Hig Rada Toksikol. 2006; 57: 445-57.
  2. Jokanovic M,Kosanovic M. Neurotoxic effects in patients poisoned with organophosphorus pesticides. Environ Toxicol Pharmacol. 2010; 29: 195-201. https://doi.org/10.1016/j.etap.2010.01.006
  3. Kovacic P. Mechanism of organophosphates (nerve gases and pesticides) and antidotes: electron transfer and oxidative stress. Curr Med Chem. 2003; 10: 2705-9. https://doi.org/10.2174/0929867033456314
  4. Shadnia S, Azizi E, Hosseini R, Khoei S, Fouladdel S, Pajoumand A, et al. Evaluation of oxidative stress and genotoxicity in Organophosphorus insecticide formulators. Hum Exp Toxicol. 2005; 24(9): 439-45. https://doi.org/10.1191/0960327105ht549oa
  5. Shah M,Iqbal M. Diazinon-induced oxidative stress and renal dysfunction in rats. Food Chem Toxicol. 2010; 48(12): 3345-53. https://doi.org/10.1016/j.fct.2010.09.003
  6. Rezaee R,Hosseinzadeh H. Safranal: From an aromatic natural product to a rewarding pharmacological agent. Iran J Basic Med Sci. 2013; 16(1): 12-26.
  7. Schmidt M, Betti G,Hensel A. Saffron in phytotherapy: pharmacology and clinical uses. Wien Med Wochen-schr. 2007; 157(13-14): 315-9. https://doi.org/10.1007/s10354-007-0428-4
  8. Alavizadeh S,Hosseinzadeh H. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem Toxicol. 2014; 64: 65-80. https://doi.org/10.1016/j.fct.2013.11.016
  9. Hosseinzadeh H,Nassiri-Asl M. Avicenna's (Ibn Sina) the Canon of Medicine and saffron (Crocus sativus): a review. Phytother Res. 2013; 27(4): 475-83. https://doi.org/10.1002/ptr.4784
  10. Rastgoo M, Hosseinzadeh H, Alavizadeh H, Abbasi A, Ayati Z,Jaafari MR. Antitumor activity of PEGylated nanoliposomes containing crocin in mice bearing C26 co-lon carcinoma. Planta Med. 2013; 79(6): 447-51. https://doi.org/10.1055/s-0032-1328363
  11. Vahdati Hassani F, Naseri V, Razavi B, Mehri S, Abnous K,Hosseinzadeh H. Antidepressant effects of crocin and its efects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. DARU J Pharmac Sci. 2014; 22(1): 16. https://doi.org/10.1186/2008-2231-22-16
  12. Amin B, Malekzadeh M, Heidari M,Hosseinzadeh H. Effect of Crocus sativus extracts and its active constituent safranal on the harmaline-induced tremor in mice. Iran J Basic Med Sci. 2015; 18(5): 449-58.
  13. Hosseinzadeh H,Talebzadeh F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia. 2005; 76(7-8): 722-4. https://doi.org/10.1016/j.fitote.2005.07.008
  14. Hosseinzadeh H, Sadeghnia HR,Rahimi A. Effect of safranal on extracellular hippocampal levels of glutamate and aspartate during kainic acid treatment in anesthetized rats. Planta Med. 2008; 74(12): 1441-5. https://doi.org/10.1055/s-2008-1081335
  15. Sadeghnia HR, Cortez MA, Liu D, Hosseinzadeh H,- Carter Snead O. Antiabsence effects of safranal in acute experimental seizure models: EEG and autoradiography. J Pharm Pharm Sci. 2008; 11(3): 1-14.
  16. Hosseinzadeh H,Khosravan V. Anticonvulsant effects of aqueous and ethanolic extracts of Crocus sativus L. stigmas in mice. Arch Iran Med. 2002; 5(1): 44-7.
  17. Razavi B,Hosseinzadeh H. Safron as an antidote or a protective agent against natural or chemical toxicities. DARU J Pharmac Sci. 2015; 1; 23: 31.
  18. Hosseinzadeh H, Modaghegh M, Safari Z. Crocus sativus L. (safron) extract and its active constituents (cro-cin and safranal) on ischemia-reperfusion in rat skeletal muscle. Evid Based Complement Alternat Med. 2009; 6(3): 343-50. https://doi.org/10.1093/ecam/nem125
  19. Hosseinzadeh H, Sadeghnia H, Ziaee T,Danaee A. Protective effect of aqueous safron extract (Crocus sativus L.) and crocin, its active constituent, on renal ischemia-reperfusion-induced oxidative damage in rats. J Pharm Pharmac Sci. 2005; 8(3): 387-93.
  20. Mehdizadeh R, Parizadeh M, Khooei A, Mehri S,Hosseinzadeh H. Cardioprotective Effect of safron extract and safranal in isoproterenol-induced myocardial infarction in Wistar rats. Iran J Basic Med Sci. 2013; 16(1): 56-63.
  21. Hosseinzadeh H,Sadeghnia H. Safranal, a constituent of Crocus sativus (safron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. J Pharm Pharmac Sci. 2005; 8(3): 394-9.
  22. Kanakis C, Tarantilis P, Pappas C, Bariyanga J, Tajmir-Riahi H,MG. P. An overview of structural features of DNA and RNA complexes with safron compounds: Models and antioxidant activity. J Photochem Photobiol B. 2009; 95(3): 204-12. https://doi.org/10.1016/j.jphotobiol.2009.03.006
  23. Hayashi M, Sofuni T,Ishidate JM. An application of acridine orange fluorescent staining to the micronuclear test. Mut Res. 1983; 120: 241-7. https://doi.org/10.1016/0165-7992(83)90096-9
  24. Ellman G, Courtney K, Andres JV,Featherstone R. A new and rapid colorimetric determination of acetyl-cholinesterase activity. Biochem Pharmacol. 1961; 7(2): 88-95. https://doi.org/10.1016/0006-2952(61)90145-9
  25. Jokanovic M,Kosanovic M. Neurotoxic effects in patients poisoned with organophosphorus pesticides. Environ Toxicol Pharmacol. 2010; 29(3): 195-201. https://doi.org/10.1016/j.etap.2010.01.006
  26. Damodar D, D'Souza UJ,Bhat S. Protective role of Vitamin E: On diazinon-induced hepatotoxicity by bio- chemical and histological alterations in wistar rats. Nat J Physiol Pharm Pharmacol. 2015; 5: 398-406. https://doi.org/10.5455/njppp.2015.5.2306201569
  27. Beydilli H, Yilmaz N, Cetin ES, Topal Y, Celik OI, Sahin C, et al. Evaluation of the protective effect of silibinin against diazinon induced hepatotoxicity and free-radical damage in rat liver. Iran Red Crescent Med J. 2015; 17(4): e25310.
  28. Hariri A, Moallem S, 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 Toxicol. 2010; 48(10): 2803-8. https://doi.org/10.1016/j.fct.2010.07.010
  29. Razavi B, Hosseinzadeh H, Movassaghi A, Imenshahidi M,Abnous K. Protective effect of crocin on diazinon induced cardiotoxicity in rats in subchronic exposure. Chem-Biol Interact. 2013; 20(3)3: 547-55.
  30. Waly M, El-Mezayen HA,Mohyee M. Potential role of curcumin and garlic acid against diazinon and propoxur hepatotoxicity. Int J Pharm Sci Rev Res. 2015; 33(2): 50-7.
  31. Abdel-Daim MM, Taha R, Ghazy EW,El-Sayed YS. Synergistic ameliorative effects of sesame oil and alpha-lipoic acid against subacute diazinon toxicity in rats: Hematological, biochemical, and antioxidant studies. Can J Physiol Pharmacol. 2015; 94(1): 81-8.
  32. Lari P, Abnous K, Imenshahidi M, Rashedinia M, Razavi M,Hosseinzadeh H. Evaluation of diazinon- induced hepatotoxicity and protective effects of crocin. Toxicol Ind Health. 2015; 31(4): 367-76. https://doi.org/10.1177/0748233713475519
  33. Chen Y, Zhang H, Tian X, Zhao C, Cai L, Liu Y, et al. Antioxidant potential of crocins and ethanol extracts of Gardenia jasminoides ELLIS and Crocus sativus L.: a relationship investigation between antioxidant activity and crocin contents. Food Chem Toxicol. 2008; 109(3): 484-92. https://doi.org/10.1016/j.foodchem.2007.09.080
  34. Moallem S, Hariri A, Mahmoudi M,Hosseinzadeh H. Effect of aqueous extract of Crocus sativus L. (safron) stigma against subacute effect of diazinon on specific biomarkers in rats. Toxicol Ind Health. 2014; 30(2): 141-6. . https://doi.org/10.1177/0748233712452609
  35. Razavi B, Hosseinzadeh H, Abnous K,Imenshahidi M. Protective effect of crocin on diazinon induced vascular toxicity in subchronic exposure in rat aorta ex-vivo. Drug Chem Toxicol. 2014; 37(4): 378-83. https://doi.org/10.3109/01480545.2013.866139
  36. Goyal SN, Arora S, Sharma AK, 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(3-4): 227-32. https://doi.org/10.1016/j.phymed.2009.08.009
  37. Puri A, Maulik SK, Ray R,Bhatnagar V. Electrocardi-ographic and biochemical evidence for the cardio-protective effect of vitamin E in doxorubicin-induced acute cardiotoxicity in rats. Eur J Pediatr Surg. 2005; 15(6): 387-91. https://doi.org/10.1055/s-2005-872923
  38. El-Shenawy NS, Al-Eisa RA, El-Salmy F,Salah O. Prophylactic effect of vitamin E against hepatotoxicity, nephrotoxicity, haematological indices and histopa-thology induced by diazinon insecticide in mice. Curr Zool. 2009; 55(3): 219-26.
  39. Yehia MAH, El-Banna SG,Okab AB. Diazinon toxicity affects histophysiological and biochemical parameters in rabbits. Exp Toxicol Pathol. 2007; 59(3-4): 215-25. https://doi.org/10.1016/j.etp.2007.09.003
  40. Kehrer JP, LG L. Pyridine nucleotides and the reduction of GSSG in hypoxic heart tissue exposed to diamide. Free Rad Biol Med. 1993; 15: 520.
  41. Campbell K. Laboratory diagnosis and investigation of anaemia. Nurs Times. 2005; 101(22): 36-9.
  42. Hariri AT, Moallem SA, M M,H. 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(6): 499-504. https://doi.org/10.1016/j.phymed.2010.10.001
  43. Shadnia S, Azizi E, Hosseini R, Khoei S, Fouladdel S, Pajoumand A, et al. Evaluation of oxidative stress and genotoxicity in organophosphorus insecticide formulators. Hum ExpToxicol. 2005; 24(9): 439-45. https://doi.org/10.1191/0960327105ht549oa
  44. Hosseinzadeh H, Abootorabi A,HR. S. Protective effect of Crocus sativus stigma extract and crocin (trans-crocin 4) on methyl methanesulfonate-induced DNA damage in mice organs. DNA Cell Biol. 2008; 27(12): 657-64. https://doi.org/10.1089/dna.2008.0767
  45. Hosseinzadeh H,Sadeghnia H. Effect of safranal, a constituent of Crocus sativus (saffron), on methyl meth- anesulfonate (MMS)-induced DNA damage in mouse organs: an alkaline single-cell gel electrophoresis (comet) assay. DNA Cell biol. 2007; 26(12): 841-6. https://doi.org/10.1089/dna.2007.0631
  46. Premkumar K, Abraham S, Santhiya S, Gopinath P,Ramesh A. Inhibition of genotoxicity by saffron (Crocus sativus L.) in mice. Drug Chem Toxicol. 2001; 24(4): 421-8. https://doi.org/10.1081/DCT-100106266