Protective effects of saffron, safranal and crocin administration on vitamins (A, D, E, K) and protein carbonyl levels against CCI4- induced oxidative damage in rats

Abstract

Objective: The possible effects of saffron and its active components on oxidative stress are known. Protein carbonyls (PCO), formed due to protein exposure to oxidizing agents, are a newly researched topic. In this study, it was aimed to determine, antioxidant fatsoluble vitamins (A, D, E, K) and PCO values after saffron, safranal and crocin administration with carbon tetrachloride (CCl4) in rats. Materials and Methods: Fifty-four Wistar albino male rats were randomly selected, and 9 groups of n=6 were formed. Vitamin levels in rat serum were determined by HPLC and PCO levels were determined by spectrophotometric method. Results: A significant difference (p<0.01) was found between the CCl4 and the saffron, safranal and crocin groups. A significant decrease was observed in retinol and cholecalciferol values between CCl4 and saffron group (p<0.05, p<0.001), and a significant decrease in cholecalciferol and phylloquinone levels between CCl4 and safranal groups (p<0.01, p<0.05). Moreover, a decrease in cholecalciferol level (p<0.05) was determined between the olive oil, saffron and CCl4+crocin groups. Conclusion: As a result, saffron and safranal have a protective effect against CCl4-induced oxidative damage to PCO, retinol, phylloquinone and cholecalciferol, and this effect may be due to the potent antioxidative effects of saffron and safranal.

Keywords

• Carbon tetrachloride
• Protein carbonyl
• Saffron
• Safranal
• Vitamin

References

1. El-Haskoury R, Al-Waili N, Kamoun Z, Makni M, Al-Waili H, Lyoussi B. Antioxidant activity and protecti ve effect of Carob honey in CCl4-induced kidney and liver injury. Arc Med Res 2018; 49: 306-13. doi.org/10.1016/j.arcmed.2018.09.011.
2. Abraham P, Wilfred G. Oxidative damage to the lipids and proteins pf the lungs, testis and kidney of rats during carbon tetrachloride intoxication. Clin Chim Acta; Inter J Clin Chem 1999; 289: 177-9. doi.org/10.1016/s0009-8981(99)00140-0.
3. Güven A, Maraşlı N, Kaya N. Karbon tetraklorür (CCl4) ve etil alkol’ün fare eritrosit antioksidan ve plazma lipid peroksidasyonuna etkisi. Kaf Üni Vet Fak Der 2003; 9: 1-4.
4. Tirkey N, Pilkhwal S, Kuhad A, Chopra K. Hesperidin, a citrus bioflavonoid, decreases the oxidative stress produced by carbon tetrachloride in rat liver and kidney. BMC Pharma 2005; 5: 2. doi.org/10.1186/1471-2210-5-2.
5. Yilmaz-Ozden T, Can A, Sancar-Bas S, Pala-Kara Z, Okyar A, Bolkent S. Protective effect of Amaranthus lividus L. on carbon tetrachloride induced hepatotoxicity in rats/Karbon tetraklorür ile sıçanlarda oluşturulan karaciğer toksisitesi üzerine Amaranthus lividus L. bitkisinin koruyucu etkisi. Turk J Biochem 2015; 40: 125-31. doi.org/10.5505/tjb.2015.05935.
6. Bakır A, Ekin S, Yüksek S, Oto G. The protective effect of Rheum Ribes L. and Quercetin on protein carbonyl levels against carbon tetrachloride-induced liver and kidney damage in the rats . Clin Exp Health Sci 2022; 12: 587-93. doi. org/10.33808/clinexphealthsci.943255.
7. Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chimica Acta 2003; 329: 23-38. doi.org/10.1016/ S0009-8981(03)00003-2.
8. Stadtman ER, Berlett BS. Reactive oxygen-mediated protein oxidation in aging and disease. Drug Met Rev 1998; 30: 225- 43. doi.org/10.3109/036.025.39808996310.

9. Reznick AZ, Packer L. Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Met in Enz 1994; 233: 357-63.doi.org/10.1016/S0076-6879(94)33041-7.
10. Yan LJ, Traber MG, Kobuchi H, Matsugo S, Tritschler HJ, Packer L. Efficacy of hypochlorous acid scavengers in the prevention of protein carbonyl formation. Archi Biochem Biophys 1996; 327: 330-334. doi.org/10.1006/abbi.1996.0130.
11. Gülbahar Ö. Protein oksidasyonunun mekanizması, önemi ve yaşlılıklar ilişkisi. Türk Geriatri Der 2007; 10: 43-8.
12. Pross A. What is life? How chemistry becomes biology? Istanbul: Metis Yayıncılık Ltd, 2017.
13. Torun F. Vitamin E nin kanserde ve kalp damar hastalıklarındaki rolü. Fab J Pharm Sci 1995; 20: 55.
14. Liden M, Eriksson U. Understanding retinol metabolism: structure and function of retinol dehydrogenases. J Bio Chem 2006; 281: 13001-4. doi.org/10.1074/jbc.R500027200.
15. Namıduru SE, Tarakçıoğlu M. K vitamini ve osteoporoz. Gaziantep Med J 2011; 17: 1-7.
16. Akkoyun H, Bayramoğlu M, Suat E, Çelebi, F. D vitamini ve metabolizma için önemi. Atatürk Üni Vet Bi Der 2014; 9: 213- 9. doi.org/10.17094/avbd.05043.
17. Sen S, Chakraborty R, Sridhar C, Reddy YSR, De B. Free radicals, antioxidants, diseases and phytomedicines: current status and future prospect. Inter J Pharma Sci R R 2010; 3: 91- 100.
18. McGimpsey JA, Douglas MH, Wallace AR. Evaluation of saffron (Crocus sativus L.) production in New Zealand. New Zealand J Crop Hort Sci 1997; 25: 159-68. doi.org/10.1080/01 140.671.1997.9514002.
19. Çınar AS , Önder A. Anadolu’nun kültürel mirası: Crocus sativus L. (Safran). FABAD J Pharm Sci 2019; 44: 79-88.
20. Abdullaev FI. Biological effects of saffron. BioFactors (Oxford, England) 1993; 4: 83-6.
21. Su Q, Rowley KG, Balazs ND. Carotenoids: separation methods applicable to biological samples. J Chro B Analyt Tec Biomed Life Sci 2002; 781: 393-418. doi.org/10.1016/S1570- 0232(02)00502-0.
22. Siluk D, Oliveira RV, Esther-Rodriguez-Rosas M, et al. A validated liquid chromatography method for the simultaneous determination of vitamins A and E in human plasma. J Pharm Biomed Anal 2007; 44: 1001-7. doi.org/10.1016/j. jpba.2007.03.033.
23. Parola M, Leonarduzzi G, Biasi F, et al. Vitamin E dietary supplementation protects against carbon tetrachloride— induced chronic liver damage and cirrhosis. Hepatology 1992; 16: 1014-21. doi.org/10.1002/hep.184.016.0426.
24. Requena JR, Levine RL, Stadtman ER. Recent advances in the analysis of oxidized proteins. Amino Acids 2003; 25: 221-6. doi.org/10.1007/s00726.003.0012-1.
25. Sarıkaya E, Doğan S. Glutathione peroxidase in health and diseases. In: Bagatini MD, ed. Glutathione System and Oxidative Stress in Health and Disease. London, 2020; 49-63.
26. Riahi-Zanjani B, Balali-Mood M, Mohammadi E, Badie- Bostan H, Memar B, Karimi G. Safranal as a safe compound to mice immune system. Avicenna J Phytome 2015; 5: 441-9.
27. Viljanen K, Kylli P, Hubbermann EM, Schwarz K, Heinonen M. Anthocyanin antioxidant activity and partition behavior in whey protein emulsion. J Agri and Food Chem 2005; 53: 2022- 27. doi.org/10.1021/jf047975d.
28. Hosseinzadeh H, Shamsaie F, Mehri S. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal. Pharma Mag 2009; 5: 419-24.
29. Bathaie SZ and Mousavi SZ. New applications and mechanisms of action of saffron and its important ingredients. Cri Rev in Food Sci and Nut 2010; 50: 761-86. doi.org/10.1080/104.083. 90902773003.
30. Bathaie SZ, Bolhassani A, Tamanoi F. Anticancer effect and molecular targets of saffron carotenoids. In The Enz 2014; 36: 57-86. doi.org/10.1016/B978-0-12-802215-3.00004-5.
31. Nanda S, Madan K. The role of Safranal and saffron stigma extracts in oxidative stress, diseases and photoaging: A systematic review. Heliyon 2021;7:e06117. (. doi.org/10.1016/j. heliyon.2021.e06117.
32. Serrano‐Díaz J, Sánchez AM, Maggi L, et al. Increasing the applications of Crocus sativus flowers as natural antioxidants. Food Sci 2012; 77: C1162-C1168. doi.org/10.1111/j1750- 3841.2012.02926.x.
33. Boskabady MH, Byrami G, Feizpour A. The effect of safranal, a constituent of Crocus sativus (saffron), on tracheal responsiveness, serum levels of cytokines, total NO and nitrite in sensitized guinea pigs. Phar Reports 2014;66, 56-61. doi. org/10.1016/j.pharep.2013.08.004.
34. Riahi-Zanjani B, Balali-Mood M, Mohammadi E, Badie- Bostan H, Memar B, Karimi G. Safranal as a safe compound to mice immune system. Avicenna J Phytomed. 2015;5:441-9.
35. Nam KN, Park YM, Jung HJ, et al. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Euro J Pharma 2010; 648: 110-6. doi.org/10.1016/j.ejphar.2010.09.003.
36. Moghaddasi MS. Saffron chemicals and medicine usage. J Med Plants Res 2010; 4:427-30.
37. Monaghan BR, Schmitt FO. The effects of carotene and of vitamin A on the oxidation of linoleic acid. J Bio Chem 1932; 96: 387-95.
38. Ötleş S, Yeşim A. Karotenoidlerin insan sağliği açisindan önemi. Pamukkale Üni Müh Bil Der 2011; 3: 249-54.
39. Traber MG, Packer L. Vitamin E: beyond antioxidant function. The Ame J of Clin Nut 1995; 62: 1501S-1509S. doi. org/10.1093/ajcn/62.6.1501S.
40. Sinbad OO, Folorunsho AA, Olabisi OL, Ayoola OA, Temitope EJ. Vitamins as antioxidants. J Food Sci and Nut Res 2019; 2: 214-35. doi: 10.26502/jfsnr.2642.110.00021.
41. Saedisomeolia A, Taheri E, Djalali M, et al. Vitamin D status and its association with antioxidant profiles in diabetic patients: A cross-sectional study in Iran. Indian J Med Sci 2013; 67: 29. doi.org/ 10.4103/0019-5359.120695.
42. Huang SJ, Lin CP, Tsai SY. Vitamin D2 content and antioxidant properties of fruit body and mycelia of edible mushrooms by UV-B irradiation. J Food Com and Analy 2015; 42: 38-45.
43. Vervoort LM, Ronden JE, Thijssen HH. The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation. Biochem Pharma 1997; 54: 871-6. doi. org/10.1016/S0006-2952(97)00254-2.
44. Levine RL. Carbonyl assay for determination of oxidatively modified proteins. Methods Enzymol 1994 ; 233: 246-57.
45. Sugandhi VV, Pangeni R, Vora LK, et al. Pharmacokinetics of vitamin dosage forms: A complete overview. Food Sci Nutr 2023;12:48-83. doi: 10.1002/fsn3.3787.
46. Yachi R, Igarashi O, Kiyose C. Protective effects of vitamin E analogs against carbon tetrachloride-induced fatty liver in rats. J Clini Biochem Nut 2010; 47: 148-54. doi.org/10.3164/ jcbn.10-35.
47. Elsisi AED, Earnest DL, Sipes IG. Vitamin A potentiation of carbon tetrachloride hepatotoxicity: role of liver macrophages and active oxygen species. Toxi App Phar 1993;119:295-301. doi.org/10.1006/taap.1993.1072.
48. Forbes JC, Taliaferro I. Increased resistance of carrot-fed rats to carbon tetrachloride. Pro Soci for Exper Bio and Med 1945; 59: 27-9. doi.org/10.3181/00379727-59-14966.
49. Alayunt NÖ, Parlak AE, Türkoğlu S, Taş F. Hepatoprotective effects of safranal on acetaminophen-induced hepatotoxicity in rats. Open Chem 2024;22:20240029. doi.org/10.1515/ chem-2024-0029.
50. Bellachioma L, Marini E, Magi G, et al. Phytochemical profiling, antibacterial and antioxidant properties of Crocus sativus flower: A comparison between tepals and stigmas. Open Chem 2022;20:431-43. doi.org/10.1515/chem- 2022-0155.