Effect of safran, safranal and crocin which are active ingredients of Saffron (Crocus) on erythrocyte fragility and hematological parameters in carbon tetrachloride intoxicated rats

Carbon tetrachloride is a toxic chemical and well known for its carcinogenic property. Intoxication with carbon tetrachloride causes serious liver injury and it is used as an experimental model for triggering liver related diseases. Saff ron (Crocus) species are well known bulbous ornamental and aromatic plants. Many of the saffron species are used in ethnomedicinal practices. In addition both saffron species and their ingredients are also subject to scientific research. In this study 72 rats were divided into 9 groups (n=8 in each group). Groups were set as control, olive oil, carbon tetrachloride, safran, safranal, crocin, carbon tetrachloride + safranal, carbon tetrachloride + crocin. Administrations were conducted for 7 days. Erythrocyte osmotic fragility and some selected hematological parameters were assessed. Results state significant increase in erythrocyte fragility due to carbon tetrachloride and amelioration due to active ingredients of saffron. Among hematocrit, hemoglobin and red blood cell count parameters only significant alteration was observed in safran with an increase in red blood cell count. Different administration schemes can be evaluated in future studies in order to assess detailed impact of saffron constituents on hematological parame ters and erythrocyte integrity.

___

1. Kus I, Ogeturk M, Oner H, et al. Protective effects of melatonin against carbon tetrachlorideinduced hepatotoxicity in rats: a light microscopic and biochemical study. Cell Biochem Funct 2005; 23: 169-174.

2. Muriel P, Alba N, Pérez-Alvarez VM, Shibayama M, Tsutsumi VK. Kupffer cells inhibition prevents hepatic lipid peroxidation and damage induced by carbon tetrachloride. Comp Biochem Physiol C Toxicol Pharmacol 2001; 130: 219-226.

3. Manibusan MK, Odin M, Eastmond DA. Postulated carbon tetrachloride mode of action: a review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2007; 25: 185-209.

4. Hong RT, Xu JM, Mei Q. Melatonin ameliorates experimental hepatic fibrosis induced by carbon tetrachloride in rats. World J Gastroenterol 2009; 15: 1452-1458.

5. Liu N, Yang Y, Mo S, Liao J, Jin J. Calcium antagonistic effects of Chinese crude drugs: preliminary investigation and evaluation by 45 Ca. Appl Radiat Isot 2005; 63: 151-155.

6. Fatehi M, Rashidabady T, Fatehi-Hassanabad Z. Effects of Crocus sativus petals' extract on rat blood pressure and on responses induced by electrical field stimulation in the rat isolated vas deferens and guinea-pig ileum. J Ethnopharmacol 2003; 84: 199-203.

7. Inoue E, Shimizu Y, Shoji M, et al. Pharmacological properties of N-095,a drug containing red ginseng, polygala root, saffron, antelope horn and aloe wood". Am J Chin Med 2005; 33: 49-60.

8. Nair SC, Kurumboor SK, Hasegawa JH. Saffron chemoprevention in biology and medicine: A review. Cancer Biother 1995; 10: 257-264.

9. Fernandez JA. Biology, biotechnology and biomedicine of saffron. Recent Res Devel Plant Sci 2004: 2127-2159.

10. Papandreou MA, Kanakis CD, Polissiou MG, et al. Inhibitory activity on amyloid-beta aggregation and antioxidant properties of Crocus sativus stigmas extract and its crocin constituents. J Agric Food Chem 2006; 54: 8762-8768.

11. Hosseinzadeh H, Sadeghnia HR. Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: Involvement of GABAergic and opioids systems. Phytomedicine 2007; 14: 256-262.

12. Hosseinzadeh H, Ghenaati J. Evaluation of the antitussive effect of stigma and petals of saffron (Crocus sativus) and its components, safranal and crocin in guinea pigs. Fitoterapia 2006; 77: 446- 448.

13. Sheng L, Qian Z, Zheng S, Xi L. Mechanism of hypolipidemic effect of crocin in rats: crocin inhibits pancreatic lipase. Eur J Pharmacol 2006; 543: 116-122.

14. Hosseinzadeh H, Talebzadeh F. Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia 2005; 76: 722-724.

15. Khalili M, Ebrahimzadeh MA, Safdari Y. Antihaemolytic activity of thirty herbal extracts in mouse red blood cells. Arh Hig Rada Toksikol 2014; 65: 399-406.

16. Suboh SM, Bilto YY, Aburjai TA. Protective effects of selected medicinal plants against protein degradation, lipid peroxidation and deformability loss of oxidatively stressed human erythrocytes. Phytother Res 2004; 18: 280-284.

17. Kolanjiappana K, Manoharana S, Kayalvizhib M. Measurement of erythrocyte lipids, lipid peroxidation, antioxidants and osmotic fragility in cervical cancer patients. Clinica Chimica Acta 2002; 326: 143-149.

18. Pagano M. Faggio C. The use of erythrocyte fragility to assess xenobiotic cytotoxicity. Cell Biochem Funct 2015; 33: 351-355.

19. Makni M, Chtourou Y, Fetoui H, et al. Erythrocyte oxidative damage in rat treated with CCl4: protective role of vanillin. Toxicol Ind Health 2012; 28: 908-916.

20. Fujita K. A study on erythrocyte-membrane osmotic resistance and periodontal changes in rats treated with carbon tetrachloride. Shikwa Gakuho 1990; 90: 727-743.

21. Dariyerli N, Toplan S, Akyolcu MC, Hatemi H, Yigit G. Erythrocyte Osmotic Fragility and Oxidative Stress in Experimental Hypothyroidism. Endocrine 2004; 25: 1-5.

22. Ozturk L, Mansour B, Yuksel M, et al. Lipid peroxidation and osmotic fragility of red blood cells in sleep-apnea patients. Clinica Chimica Acta 2003; 332: 83-88.

23. Mojzis J, Nicák A, Guzy J, Kron I, Mirossay L. Effect of stobadine on carbon tetrachlorideinduced erythrocyte membrane changes in rats. Free Radic Biol Med 1998; 24: 1347-1351.

24. Saba AB, Oyagbemi AA, Azeez OI. Amelioration of carbon tetrachloride-induced hepatotoxicity and haemotoxicity by aqueous leaf extract of Cnidoscolus aconitifolius in rats. Niger J Physiol Sci 2010; 28: 139-147.

25. El-Beshbishy HA, Hassan MH, Aly HA, Doghish AS, Alghaithy AA. Crocin "saffron" protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antioxidant enzymes. Ecotoxicol Environ Saf 2012; 83: 47-54.

26. Sebastin Santhosh M, Hemshekhar M, Thushara RM, et al. Vipera russelli venom-induced oxidative stress and hematological alterations: Amelioration by crocin a dietary colorant. Cell Biochem Funct 2013; 31: 41-50.

27. el Daly ES. 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.