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Review Article

Anti-toxicant Properties of Saffron and Relevance to Protection from Toxins and Drugs

Author(s): Kyriaki Hatziagapiou* and George I. Lambrou*

Volume 16, Issue 3, 2020

Page: [265 - 283] Pages: 19

DOI: 10.2174/1573407214666181003123707

Price: $65

Abstract

Background: Reactive oxygen species and reactive nitrogen species, which are collectively called reactive oxygen nitrogen species, are inevitable by-products of cellular metabolic redox reactions, such as oxidative phosphorylation in the mitochondrial respiratory chain, phagocytosis, reactions of biotransformation of exogenous and endogenous substrata in endoplasmic reticulum, eicosanoid synthesis, and redox reactions in the presence of metal with variable valence. Among medicinal plants there is a growing interest in Crocus sativus L. It is a perennial, stemless herb, belonging to Iridaceae family, cultivated in various countries such as Greece, Italy, Spain, Israel, Morocco, Turkey, Iran, India, China, Egypt and Mexico.

Objectives: The present study aims to address the anti-toxicant role of Crocus sativus L. in the cases of toxin and drug toxification.

Materials and Methods: An electronic literature search was conducted by the two authors from 1993 to August 2017. Original articles and systematic reviews (with or without meta-analysis), as well as case reports were selected. Titles and abstracts of papers were screened by a third reviewer to determine whether they met the eligibility criteria, and full texts of the selected articles were retrieved.

Results: The authors focused on literature concerning the role of Crocus Sativus L. as an anti-toxicant agent. Literature review showed that Saffron is a potent anti-toxicant agent with a plethora of applications ranging from anti-oxidant properties, to chemotherapy protective effects.

Conclusion: Literature findings represented in current review herald promising results for using Crocus Sativus L. and/or its active constituents as anti-toxicant, chemotherapy-induced protection and toxin protection.

Keywords: saffron, crocin, crocetin, safranal, oxidative stress, chemotherapy, toxins.

Graphical Abstract

[1]
Adibhatla, R.M.; Hatcher, J.F. Lipid oxidation and peroxidation in CNS health and disease: from molecular mechanisms to therapeutic opportunities. Antioxid. Redox Signal., 2010, 12(1), 125-169.
[http://dx.doi.org/10.1089/ars.2009.2668] [PMID: 19624272]
[2]
Bar-Or, D.; Bar-Or, R.; Rael, L.T.; Brody, E.N. Oxidative stress in severe acute illness. Redox Biol., 2015, 4, 340-345.
[http://dx.doi.org/10.1016/j.redox.2015.01.006] [PMID: 25644686]
[3]
Collard, C.D.; Gelman, S. Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury. Anesthesiology, 2001, 94(6), 1133-1138.
[http://dx.doi.org/10.1097/00000542-200106000-00030] [PMID: 11465607]
[4]
Fakhruddin, S.; Alanazi, W.; Jackson, K.E. Diabetes-induced reactive oxygen species: Mechanism of their generation and role in renal injury. J. Diabetes Res., 2017, 20178379327
[http://dx.doi.org/10.1155/2017/8379327] [PMID: 28164134]
[5]
Giacco, F.; Brownlee, M. Oxidative stress and diabetic complications. Circ. Res., 2010, 107(9), 1058-1070.
[http://dx.doi.org/10.1161/CIRCRESAHA.110.223545] [PMID: 21030723]
[6]
Jnaneshwari, S.; Hemshekhar, M.; Santhosh, M.S.; Sunitha, K.; Thushara, R.; Thirunavukkarasu, C.; Kemparaju, K.; Girish, K.S. Crocin, a dietary colorant, mitigates cyclophosphamide-induced organ toxicity by modulating antioxidant status and inflammatory cytokines. J. Pharm. Pharmacol., 2013, 65(4), 604-614.
[http://dx.doi.org/10.1111/jphp.12016] [PMID: 23488790]
[7]
Lushchak, V.I. Free radicals, reactive oxygen species, oxidative stress and its classification. Chem. Biol. Interact., 2014, 224, 164-175.
[http://dx.doi.org/10.1016/j.cbi.2014.10.016] [PMID: 25452175]
[8]
Massaad, C.A.; Amin, S.K.; Hu, L.; Mei, Y.; Klann, E.; Pautler, R.G. Mitochondrial superoxide contributes to blood flow and axonal transport deficits in the Tg2576 mouse model of Alzheimer’s disease. PLoS One, 2010, 5(5)e10561
[http://dx.doi.org/10.1371/journal.pone.0010561] [PMID: 20479943]
[9]
Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007, 39(1), 44-84.
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID: 16978905]
[10]
Yan, L.J. Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress. J. Diabetes Res., 2014, 2014137919
[http://dx.doi.org/10.1155/2014/137919] [PMID: 25019091]
[11]
Ivanenkov, Y.; Chufarova, N.; Veselov, M.; Majouga, A. Dietary polyphenols for prostate cancer therapy. Curr. Bioact. Compd., 2014, 10(2), 76-111.
[http://dx.doi.org/10.2174/157340721002141001102524]
[12]
Kawano, D.F.; Taft, C.A.; da Silva, C.H.T.P. Prospecting for new inhibitors of anaplastic lymphoma kinase, a clinically relevant oncogenic drug target. Curr. Bioact. Compd., 2017, 13(3), 236-243.
[http://dx.doi.org/10.2174/1573407212666160607092819]
[13]
Kovacic, P.; Somanathan, R. Nitric oxide, peroxynitrite, peroxynitrous acid, nitroxyl, nitrogen dioxide, nitrous oxide: Biochemical mechanisms and bioaction. Curr. Bioact. Compd., 2013, 8(4), 297-306.
[http://dx.doi.org/10.2174/1573407211208040001]
[14]
Perez, C.A.; Tong, Y.; Guo, M. Iron chelators as potential therapeutic agents for parkinson’s disease. Curr. Bioact. Compd., 2008, 4(3), 150-158.
[http://dx.doi.org/10.2174/157340708786305952] [PMID: 19809592]
[15]
Ahmadinejad, F.; Geir Møller, S.; Hashemzadeh-Chaleshtori, M.; Bidkhori, G.; Jami, M.S. Molecular mechanisms behind free radical scavengers function against oxidative stress. Antioxidants, 2017, 6(3)E51
[http://dx.doi.org/10.3390/antiox6030051] [PMID: 28698499]
[16]
Ozcan, A.; Ogun, M. Biochemistry of reactive oxygen and nitrogen speciesBasic principles and clinical significance of oxidative stress;Gowder, S.J.T., Ed.; InTechOpen: London , 2015. Vol. 1, pp. 38-58.
[http://dx.doi.org/10.5772/61193]
[17]
Schieber, M.; Chandel, N.S. ROS function in redox signaling and oxidative stress. Curr. Biol., 2014, 24(10), R453-R462.
[http://dx.doi.org/10.1016/j.cub.2014.03.034] [PMID: 24845678]
[18]
Thapa, A.; Carroll, N.J. Dietary modulation of oxidative stress in alzheimer’s disease. Int. J. Mol. Sci., 2017, 18(7)E1583
[http://dx.doi.org/10.3390/ijms18071583] [PMID: 28753984]
[19]
Rehman, S.; Khan, H. Advances in antioxidant potential of natural alkaloids. Curr. Bioact. Compd., 2017, 13(2), 101-108.
[http://dx.doi.org/10.2174/1573407212666160614075157]
[20]
Andreoli, T.E. Free radicals and oxidative stress. Am. J. Med., 2000, 108(8), 650-651.
[http://dx.doi.org/10.1016/S0002-9343(00)00418-6] [PMID: 10856413]
[21]
Cobb, C.A.; Cole, M.P. Oxidative and nitrative stress in neurodegeneration. Neurobiol. Dis., 2015, 84(Suppl. C), 4-21.
[http://dx.doi.org/10.1016/j.nbd.2015.04.020] [PMID: 26024962]
[22]
Guo, C.; Sun, L.; Chen, X.; Zhang, D. Oxidative stress, mitochondrial damage and neurodegenerative diseases. Neural Regen. Res., 2013, 8(21), 2003-2014.
[PMID: 25206509]
[23]
Liu, Z.; Zhou, T.; Ziegler, A.C.; Dimitrion, P.; Zuo, L. Oxidative stress in neurodegenerative diseases: From molecular mechanisms to clinical applications. Oxid. Med. Cell. Longev., 2017, 20172525967
[http://dx.doi.org/10.1155/2017/2525967] [PMID: 28785371]
[24]
Sies, H. Oxidative stress: a concept in redox biology and medicine. Redox Biol., 2015, 4, 180-183.
[http://dx.doi.org/10.1016/j.redox.2015.01.002] [PMID: 25588755]
[25]
Ye, Z.W.; Zhang, J.; Townsend, D.M.; Tew, K.D. Oxidative stress, redox regulation and diseases of cellular differentiation. Biochim. Biophys. Acta, 2015, 1850(8), 1607-1621.
[http://dx.doi.org/10.1016/j.bbagen.2014.11.010] [PMID: 25445706]
[26]
de Fatima, A.; Modolo, L.; Neres, A.T.; Ferreira, C.; de Souza, A.C. Curcumin conjugates and metallocomplexes as lead compounds for development of anticancer agents - a short review. Curr. Bioact. Compd., 2008, 4(3), 189-199.
[http://dx.doi.org/10.2174/157340708786305934]
[27]
Dasuri, K.; Zhang, L.; Keller, J.N. Oxidative stress, neurodegeneration, and the balance of protein degradation and protein synthesis. Free Radic. Biol. Med., 2013, 62, 170-185.
[http://dx.doi.org/10.1016/j.freeradbiomed.2012.09.016] [PMID: 23000246]
[28]
Ljubisavljevic, S. Oxidative stress and neurobiology of demyelination. Mol. Neurobiol., 2016, 53(1), 744-758.
[http://dx.doi.org/10.1007/s12035-014-9041-x] [PMID: 25502298]
[29]
Liu, Z.; Wen, X. A systematic review of a naturally occurring iridoid: Catalpol. Curr. Bioact. Compd., 2013, 9(4), 306-323.
[http://dx.doi.org/10.2174/1573407209666131230233706]
[30]
La Cava, A. The effects of curcumin on immune responses. Curr. Bioact. Compd., 2012, 8(2), 142-145.
[http://dx.doi.org/10.2174/157340712801784741]
[31]
Massaad, C.A. Neuronal and vascular oxidative stress in Alzheimer’s disease. Curr. Neuropharmacol., 2011, 9(4), 662-673.
[http://dx.doi.org/10.2174/157015911798376244] [PMID: 22654724]
[32]
Palozza, P.C.; Mele, M.; Cittadini, A.; Mastrantoni, M. Potential interactions of carotenoids with other bioactive food components in the prevention of chronic diseases. Curr. Bioact. Compd., 2011, 7(4), 243-261.
[http://dx.doi.org/10.2174/157340711798375877]
[33]
Gagez, A-L.; Thiery, V.; Pasquet, V.; Cadoret, J-P.; Picot, L. Epoxycarotenoids and cancer. Curr. Bioact. Compd.,, 2012, 8(2), 109-141. [Review].
[http://dx.doi.org/10.2174/157340712801784787]
[34]
Maity, B.; Chattopadhyay, S. Natural antiulcerogenic agents: An overview. Curr. Bioact. Compd., 2008, 4(4), 225-244.
[http://dx.doi.org/10.2174/157340708786847889]
[35]
Finley, J.W.; Gao, S. A perspective on Crocus sativus l. (saffron) constituent crocin: A potent water-soluble antioxidant and potential therapy for alzheimer’s disease. J. Agric. Food Chem., 2017, 65(5), 1005-1020.
[http://dx.doi.org/10.1021/acs.jafc.6b04398] [PMID: 28098452]
[36]
Rahaiee, S.; Moini, S.; Hashemi, M.; Shojaosadati, S.A. Evaluation of antioxidant activities of bioactive compounds and various extracts obtained from saffron (Crocus sativus L.): a review. J. Food Sci. Technol., 2015, 52(4), 1881-1888.
[http://dx.doi.org/10.1007/s13197-013-1238-x] [PMID: 25829569]
[37]
Christodoulou, E.; Kadoglou, N.P.; Kostomitsopoulos, N.; Valsami, G. Saffron: a natural product with potential pharmaceutical applications. J. Pharm. Pharmacol., 2015, 67(12), 1634-1649.
[http://dx.doi.org/10.1111/jphp.12456] [PMID: 26272123]
[38]
Patel, S.; Sarwat, M.; Khan, T.H. Mechanism behind the anti-tumour potential of saffron (Crocus sativus L.): The molecular perspective. Crit. Rev. Oncol. Hematol., 2017, 115, 27-35.
[http://dx.doi.org/10.1016/j.critrevonc.2017.04.010] [PMID: 28602167]
[39]
Amin, A.; Hamza, A.A.; Bajbouj, K.; Ashraf, S.S.; Daoud, S. Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology, 2011, 54(3), 857-867.
[http://dx.doi.org/10.1002/hep.24433] [PMID: 21607999]
[40]
Hosseinzadeh, H.; Abootorabi, A.; Sadeghnia, H.R. 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), 657-664.
[http://dx.doi.org/10.1089/dna.2008.0767] [PMID: 18788978]
[41]
Hosseinzadeh, H.; Sadeghnia, H.R.; 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., 2005, 8(3), 387-393.
[PMID: 16401388]
[42]
Schmidt, M.; Betti, G.; Hensel, A. Saffron in phytotherapy: pharmacology and clinical uses. Wien. Med. Wochenschr., 2007, 157(13-14), 315-319.
[http://dx.doi.org/10.1007/s10354-007-0428-4] [PMID: 17704979]
[43]
Winterhalter, P.; Straubinger, M. Saffron-renewed interest in an ancient spice. Food Rev. Int., 2000, 16(1), 39-59.
[http://dx.doi.org/10.1081/FRI-100100281]
[44]
Alavizadeh, S.H.; Hosseinzadeh, H. Bioactivity assessment and toxicity of crocin: a comprehensive review. Food Chem. Toxicol., 2014, 64, 65-80.
[http://dx.doi.org/10.1016/j.fct.2013.11.016] [PMID: 24275090]
[45]
Bolhassani, A.; Khavari, A.; Bathaie, S.Z. Saffron and natural carotenoids: Biochemical activities and anti-tumor effects. Biochim. Biophys. Acta, 2014, 1845(1), 20-30.
[PMID: 24269582]
[46]
Caballero-Ortega, H.; Pereda-Miranda, R.; Abdullaev, F.I. Hplc quantification of major active components from 11 different saffron (Crocus sativus L.) sources. Food Chem., 2007, 100(3), 1126-1131.
[http://dx.doi.org/10.1016/j.foodchem.2005.11.020]
[47]
Giaccio, M. Crocetin from saffron: an active component of an ancient spice. Crit. Rev. Food Sci. Nutr., 2004, 44(3), 155-172.
[http://dx.doi.org/10.1080/10408690490441433] [PMID: 15239370]
[48]
Liakopoulou-Kyriakides, M.; Kyriakidis, D.A. Crocus sativus-biological active constitutents Studies in natural products chemistry; Atta-ur-Rahman; Ed.; Elsevier B.V.: Amsterdam,. , 2002, Vol. 26, pp. 293-312.
[49]
Assimopoulou, A.N.; Sinakos, Z.; Papageorgiou, V.P. Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytother. Res., 2005, 19(11), 997-1000.
[http://dx.doi.org/10.1002/ptr.1749] [PMID: 16317646]
[50]
Bathaie, S.Z.; Mousavi, S.Z. New applications and mechanisms of action of saffron and its important ingredients. Crit. Rev. Food Sci. Nutr., 2010, 50(8), 761-786.
[http://dx.doi.org/10.1080/10408390902773003] [PMID: 20830635]
[51]
Gutheil, W.G.; Reed, G.; Ray, A.; Anant, S.; Dhar, A. Crocetin: an agent derived from saffron for prevention and therapy for cancer. Curr. Pharm. Biotechnol., 2012, 13(1), 173-179.
[http://dx.doi.org/10.2174/138920112798868566] [PMID: 21466430]
[52]
Tarantilis, P.A.; Tsoupras, G.; Polissiou, M. Determination of saffron (Crocus sativus L.) components in crude plant extract using high-performance liquid chromatography-UV-visible photodiode-array detection-mass spectrometry. J. Chromatogr. A, 1995, 699(1-2), 107-118.
[http://dx.doi.org/10.1016/0021-9673(95)00044-N] [PMID: 7757208]
[53]
Babaei, A.; Arshami, J.; Haghparast, A.; Danesh Mesgaran, M. Effects of saffron (Crocus sativus) petal ethanolic extract on hematology, antibody response, and spleen histology in rats. Avicenna J. Phytomed., 2014, 4(2), 103-109.
[PMID: 25050307]
[54]
Bostan, H.B.; Mehri, S.; Hosseinzadeh, H. Toxicology effects of saffron and its constituents: a review. Iran. J. Basic Med. Sci., 2017, 20(2), 110-121.
[PMID: 28293386]
[55]
Feizzadeh, B.; Afshari, J.T.; Rakhshandeh, H.; Rahimi, A.; Brook, A.; Doosti, H. Cytotoxic effect of saffron stigma aqueous extract on human transitional cell carcinoma and mouse fibroblast. Urol. J., 2008, 5(3), 161-167.
[PMID: 18825622]
[56]
Milajerdi, A.; Djafarian, K.; Hosseini, B. The toxicity of saffron (Crocus sativus L.) and its constituents against normal and cancer cells. J. Nutr. Intermed. Metab., 2016, 3(Suppl. C), 23-32.
[http://dx.doi.org/10.1016/j.jnim.2015.12.332]
[57]
Mousavi, S.H.; Tayarani, N.Z.; Parsaee, H. Protective effect of saffron extract and crocin on reactive oxygen species-mediated high glucose-induced toxicity in PC12 cells. Cell. Mol. Neurobiol., 2010, 30(2), 185-191.
[http://dx.doi.org/10.1007/s10571-009-9441-z] [PMID: 19711182]
[58]
Shati, A.A.; Elsaid, F.G.; Hafez, E.E. Biochemical and molecular aspects of aluminium chloride-induced neurotoxicity in mice and the protective role of Crocus sativus L. extraction and honey syrup. Neuroscience, 2011, 175, 66-74.
[http://dx.doi.org/10.1016/j.neuroscience.2010.11.043] [PMID: 21115102]
[59]
Abdullaev, F.I.; Riverón-Negrete, L.; Caballero-Ortega, H.; Manuel Hernández, J.; Pérez-López, I.; Pereda-Miranda, R.; Espinosa-Aguirre, J.J. Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.). Toxicol. In Vitro, 2003, 17(5-6), 731-736.
[http://dx.doi.org/10.1016/S0887-2333(03)00098-5] [PMID: 14599470]
[60]
Meng, L.; Teng, Z.; Zheng, N.; Meng, W.; Dai, R.; Deng, Y. Effect of quaternary ammonium carboxymethylchitosan on release rate in-vitro of aspirin sustained-release matrix tablets. Iran. J. Pharm. Res., 2013, 12(3), 221-230.
[PMID: 24250627]
[61]
Ayatollahi, H.; Javan, A.O.; Khajedaluee, M.; Shahroodian, M.; Hosseinzadeh, H. Effect of Crocus sativus L. (saffron) on coagulation and anticoagulation systems in healthy volunteers. Phytother. Res., 2014, 28(4), 539-543.
[http://dx.doi.org/10.1002/ptr.5021] [PMID: 23733488]
[62]
Modaghegh, M.H.; Shahabian, M.; Esmaeili, H.A.; Rajbai, O.; Hosseinzadeh, H. Safety evaluation of saffron (Crocus sativus) tablets in healthy volunteers. Phytomedicine, 2008, 15(12), 1032-1037.
[http://dx.doi.org/10.1016/j.phymed.2008.06.003] [PMID: 18693099]
[63]
Mohamadpour, A.H.; Ayati, Z.; Parizadeh, M.R.; Rajbai, O.; Hosseinzadeh, H. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iran. J. Basic Med. Sci., 2013, 16(1), 39-46.
[PMID: 23638291]
[64]
Kanakis, C.D.; Tarantilis, P.A.; Tajmir-Riahi, H.A.; Polissiou, M.G. Crocetin, dimethylcrocetin, and safranal bind human serum albumin: stability and antioxidative properties. J. Agric. Food Chem., 2007, 55(3), 970-977.
[http://dx.doi.org/10.1021/jf062638l] [PMID: 17263501]
[65]
Kanakis, C.D.; Tarantilis, P.A.; Tajmir-Riahi, H.A.; Polissiou, M.G. DNA interaction with saffron’s secondary metabolites safranal, crocetin, and dimethylcrocetin. DNA Cell Biol., 2007, 26(1), 63-70.
[http://dx.doi.org/10.1089/dna.2006.0529] [PMID: 17263598]
[66]
Kanakis, C.D.; Tarantilis, P.A.; Tajmir-Riahi, H.A.; Polissiou, M.G. Interaction of trna with safranal, crocetin, and dimethylcrocetin. J. Biomol. Struct. Dyn., 2007, 24(6), 537-546.
[http://dx.doi.org/10.1080/07391102.2007.10507142] [PMID: 17508775]
[67]
Karimi, E.; Oskoueian, E.; Hendra, R.; Jaafar, H.Z. Evaluation of Crocus sativus L. stigma phenolic and flavonoid compounds and its antioxidant activity. Molecules, 2010, 15(9), 6244-6256.
[http://dx.doi.org/10.3390/molecules15096244] [PMID: 20877220]
[68]
Kanakis, C.D.; Tarantilis, P.A.; Pappas, C.; Bariyanga, J.; Tajmir-Riahi, H.A.; Polissiou, M.G. An overview of structural features of DNA and RNA complexes with saffron compounds: Models and antioxidant activity. J. Photochem. Photobiol. B, 2009, 95(3), 204-212.
[http://dx.doi.org/10.1016/j.jphotobiol.2009.03.006] [PMID: 19395270]
[69]
Ordoudi, S.A.; Befani, C.D.; Nenadis, N.; Koliakos, G.G.; Tsimidou, M.Z. Further examination of antiradical properties of Crocus sativus stigmas extract rich in crocins. J. Agric. Food Chem., 2009, 57(8), 3080-3086.
[http://dx.doi.org/10.1021/jf804041g] [PMID: 19284715]
[70]
LoPachin, R.M.; Gavin, T. Molecular mechanism of acrylamide neurotoxicity: lessons learned from organic chemistry. Environ. Health Perspect., 2012, 120(12), 1650-1657.
[http://dx.doi.org/10.1289/ehp.1205432] [PMID: 23060388]
[71]
Prasad, S.N.; Muralidhara, Evidence of acrylamide induced oxidative stress and neurotoxicity in Drosophila melanogaster - its amelioration with spice active enrichment: relevance to neuropathy. Neurotoxicology, 2012, 33(5), 1254-1264.
[http://dx.doi.org/10.1016/j.neuro.2012.07.006] [PMID: 22841601]
[72]
Prasad, S.N.; Muralidhara, Mitigation of acrylamide-induced behavioral deficits, oxidative impairments and neurotoxicity by oral supplements of geraniol (a monoterpene) in a rat model. Chem. Biol. Interact., 2014, 223, 27-37.
[http://dx.doi.org/10.1016/j.cbi.2014.08.016] [PMID: 25199698]
[73]
Yousef, M.I.; El-Demerdash, F.M. Acrylamide-induced oxidative stress and biochemical perturbations in rats. Toxicology, 2006, 219(1-3), 133-141.
[http://dx.doi.org/10.1016/j.tox.2005.11.008] [PMID: 16343728]
[74]
Mehri, S.; Abnous, K.; Mousavi, S.H.; Shariaty, V.M.; Hosseinzadeh, H. Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12 cells. Cell. Mol. Neurobiol., 2012, 32(2), 227-235.
[http://dx.doi.org/10.1007/s10571-011-9752-8] [PMID: 21901509]
[75]
Mehri, S.; Abnous, K.; Khooei, A.; Mousavi, S.H.; Shariaty, V.M.; Hosseinzadeh, H. Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress. Iran. J. Basic Med. Sci., 2015, 18(9), 902-908.
[PMID: 26523222]
[76]
Subramaniam, S.R.; Chesselet, M.F. Mitochondrial dysfunction and oxidative stress in Parkinson’s disease. Prog. Neurobiol., 2013, 106-107, 17-32.
[http://dx.doi.org/10.1016/j.pneurobio.2013.04.004] [PMID: 23643800]
[77]
Tanner, C.M.; Kamel, F.; Ross, G.W.; Hoppin, J.A.; Goldman, S.M.; Korell, M.; Marras, C.; Bhudhikanok, G.S.; Kasten, M.; Chade, A.R.; Comyns, K.; Richards, M.B.; Meng, C.; Priestley, B.; Fernandez, H.H.; Cambi, F.; Umbach, D.M.; Blair, A.; Sandler, D.P.; Langston, J.W. Rotenone, paraquat, and Parkinson’s disease. Environ. Health Perspect., 2011, 119(6), 866-872.
[http://dx.doi.org/10.1289/ehp.1002839] [PMID: 21269927]
[78]
Rao, S.V.; Muralidhara, ; Yenisetti, S.C.; Rajini, P.S. Evidence of neuroprotective effects of saffron and crocin in a Drosophila model of parkinsonism. Neurotoxicology, 2016, 52, 230-242.
[http://dx.doi.org/10.1016/j.neuro.2015.12.010] [PMID: 26705857]
[79]
Pan, P.K.; Qiao, L.Y.; Wen, X.N. Safranal prevents rotenone-induced oxidative stress and apoptosis in an in vitro model of Parkinson’s disease through regulating Keap1/Nrf2 signaling pathway. Cell. Mol. Biol., 2016, 62(14), 11-17.
[http://dx.doi.org/10.14715/cmb/2016.62.14.2] [PMID: 28145852]
[80]
Prediger, R.D.; Aguiar, A.S., Jr; Moreira, E.L.; Matheus, F.C.; Castro, A.A.; Walz, R.; De Bem, A.F.; Latini, A.; Tasca, C.I.; Farina, M.; Raisman-Vozari, R. The intranasal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): a new rodent model to test palliative and neuroprotective agents for Parkinson’s disease. Curr. Pharm. Des., 2011, 17(5), 489-507.
[http://dx.doi.org/10.2174/138161211795164095] [PMID: 21375482]
[81]
Schmidt, N.; Ferger, B. Neurochemical findings in the MPTP model of Parkinson’s disease. J. Neural Transm. (Vienna), 2001, 108(11), 1263-1282.
[http://dx.doi.org/10.1007/s007020100004] [PMID: 11768626]
[82]
Purushothuman, S.; Nandasena, C.; Peoples, C.L.; El Massri, N.; Johnstone, D.M.; Mitrofanis, J.; Stone, J. Saffron pre-treatment offers neuroprotection to Nigral and retinal dopaminergic cells of MPTP-Treated mice. J. Parkinsons Dis., 2013, 3(1), 77-83.
[http://dx.doi.org/10.3233/JPD-130173] [PMID: 23938314]
[83]
Zhang, G.F.; Zhang, Y.; Zhao, G. Crocin protects PC12 cells against MPP(+)-induced injury through inhibition of mitochondrial dysfunction and ER stress. Neurochem. Int., 2015, 89, 101-110.
[http://dx.doi.org/10.1016/j.neuint.2015.07.011] [PMID: 26209153]
[84]
Hoshyar, R.; Bathaie, S.Z.; Kyani, A.; Mousavi, M.F. Is there any interaction between telomeric DNA structures, G-quadruplex and I-motif, with saffron active metabolites? Nucleosides Nucleotides Nucleic Acids, 2012, 31(11), 801-812.
[http://dx.doi.org/10.1080/15257770.2012.730164] [PMID: 23145950]
[85]
Bathaie, S.Z.; Bolhasani, A.; Hoshyar, R.; Ranjbar, B.; Sabouni, F.; Moosavi-Movahedi, A.A. Interaction of saffron carotenoids as anticancer compounds with ctDNA, Oligo (dG.dC)15, and Oligo (dA.dT)15. DNA Cell Biol., 2007, 26(8), 533-540.
[http://dx.doi.org/10.1089/dna.2007.0598] [PMID: 17688404]
[86]
Ashrafi, M.; Bathaie, S.Z.; Taghikhani, M.; Moosavi-Movahedi, A.A. The effect of carotenoids obtained from saffron on histone H1 structure and H1-DNA interaction. Int. J. Biol. Macromol., 2005, 36(4), 246-252.
[http://dx.doi.org/10.1016/j.ijbiomac.2005.05.008] [PMID: 16087230]
[87]
Dhar, A.; Mehta, S.; Dhar, G.; Dhar, K.; Banerjee, S.; Van Veldhuizen, P.; Campbell, D.R.; Banerjee, S.K. Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol. Cancer Ther., 2009, 8(2), 315-323.
[http://dx.doi.org/10.1158/1535-7163.MCT-08-0762] [PMID: 19208826]
[88]
Hosseinzadeh, H.; Sadeghnia, H.R. Effect of safranal, a constituent of Crocus sativus (saffron), on methyl methanesulfonate (MMS)-induced DNA damage in mouse organs: an alkaline single-cell gel electrophoresis (comet) assay. DNA Cell Biol., 2007, 26(12), 841-846.
[http://dx.doi.org/10.1089/dna.2007.0631] [PMID: 17854266]
[89]
Premkumar, K.; Abraham, S.K.; Santhiya, S.T.; Gopinath, P.M.; Ramesh, A. Inhibition of genotoxicity by saffron (Crocus sativus L.) in mice. Drug Chem. Toxicol., 2001, 24(4), 421-428.
[http://dx.doi.org/10.1081/DCT-100106266] [PMID: 11665650]
[90]
Premkumar, K.; Abraham, S.K.; Santhiya, S.T.; Ramesh, A. Protective effects of saffron (Crocus sativus Linn.) on genotoxins-induced oxidative stress in Swiss albino mice. Phytother. Res., 2003, 17(6), 614-617.
[http://dx.doi.org/10.1002/ptr.1209] [PMID: 12820227]
[91]
Premkumar, K.; Thirunavukkarasu, C.; Abraham, S.K.; Santhiya, S.T.; Ramesh, A. Protective effect of saffron (Crocus sativus L.) aqueous extract against genetic damage induced by anti-tumor agents in mice. Hum. Exp. Toxicol., 2006, 25(2), 79-84.
[http://dx.doi.org/10.1191/0960327106ht589oa] [PMID: 16539212]
[92]
Nair, S.C.; Panikkar, K.R.; Parthod, R.K. Protective effects of crocetin on the bladder toxicity induced by cyclophosphamide. Cancer Biother., 1993, 8(4), 339-343.
[http://dx.doi.org/10.1089/cbr.1993.8.339] [PMID: 7804375]
[93]
Premkumar, K.; Kavitha, S.; Santhiya, S.T.; Ramesh, A.R.; Suwanteerangkul, J. Interactive effects of saffron with garlic and curcumin against cyclophosphamide induced genotoxicity in mice. Asia Pac. J. Clin. Nutr., 2004, 13(3), 292-294.
[PMID: 15331343]
[94]
Bakhtiary, Z.; Shahrooz, R.; Ahmadi, A.; Zarei, L. Evaluation of antioxidant effects of crocin on sperm quality in cyclophosphamide treated adult mice. Vet. Res. Forum, 2014, 5(3), 213-218.
[PMID: 25568721]
[95]
Carrell, D.T.; Emery, B.R.; Hammoud, S. Altered protamine expression and diminished spermatogenesis: what is the link? Hum. Reprod. Update, 2007, 13(3), 313-327.
[http://dx.doi.org/10.1093/humupd/dml057] [PMID: 17208950]
[96]
Gill-Sharma, M.K.; Choudhuri, J.; D’Souza, S. Sperm chromatin protamination: an endocrine perspective. Protein Pept. Lett., 2011, 18(8), 786-801.
[http://dx.doi.org/10.2174/092986611795714005] [PMID: 21443490]
[97]
Paterson, R.M.; Sariah, M.; Lima, N.; Zainal, M.A.; Santos, C. Mutagenic and inhibitory compounds produced by fungi affect detrimentally diagnosis and phylogenetic analyses. Curr. Bioact. Compd., 2008, 4(4), 245-257.
[http://dx.doi.org/10.2174/157340708786847906]
[98]
Kew, M.C. Aflatoxins as a cause of hepatocellular carcinoma. J. Gastrointestin. Liver Dis., 2013, 22(3), 305-310.
[PMID: 24078988]
[99]
Wang, C.J.; Shiah, H.S.; Lin, J.K. Modulatory effect of crocetin on aflatoxin B1 cytotoxicity and DNA adduct formation in C3H10T1/2 fibroblast cell. Cancer Lett., 1991, 56(1), 1-10.
[http://dx.doi.org/10.1016/0304-3835(91)90186-L] [PMID: 1900736]
[100]
Wang, C.J.; Hsu, J.D.; Lin, J.K. Suppression of aflatoxin B1-induced hepatotoxic lesions by crocetin (a natural carotenoid). Carcinogenesis, 1991, 12(10), 1807-1810.
[http://dx.doi.org/10.1093/carcin/12.10.1807] [PMID: 1934261]
[101]
Das, I.; Chakrabarty, R.N.; Das, S. Saffron can prevent chemically induced skin carcinogenesis in Swiss albino mice. Asian Pac. J. Cancer Prev., 2004, 5(1), 70-76.
[PMID: 15075009]
[102]
Das, I.; Das, S.; Saha, T. Saffron suppresses oxidative stress in DMBA-induced skin carcinoma: A histopathological study. Acta Histochem., 2010, 112(4), 317-327.
[http://dx.doi.org/10.1016/j.acthis.2009.02.003] [PMID: 19328523]
[103]
Gowder, S.; Devaraj, H. A review of the nephrotoxicity of the food flavor cinnamaldehyde. Curr. Bioact. Compd., 2010, 6(2), 106-117.
[http://dx.doi.org/10.2174/157340710791184877]
[104]
Singh, A.; Ahmad, I.; Akhter, S.; Zaki Ahmad, M.; Iqbal, Z.; Ahmad, J.; Thymoquinone, F. Major molecular targets, prominent pharmacological actions and drug delivery concerns. Curr. Bioact. Compd., 2013, 8(4), 334-344.
[http://dx.doi.org/10.2174/1573407211208040003]
[105]
Abe, R.; Okano, J.I.; Imamoto, R.; Fujise, Y.; Murawaki, Y. Sequential analysis of diethylnitrosamine-induced hepatocarcinogenesis in rats. Exp. Ther. Med., 2012, 3(3), 371-378.
[http://dx.doi.org/10.3892/etm.2011.419] [PMID: 22969898]
[106]
Agrawal, A.; Sharma, M.; Rai, S.K.; Singh, B.; Tiwari, M.; Chandra, R. The effect of the aqueous extract of the roots of Asparagus racemosus on hepatocarcinogenesis initiated by diethylnitrosamine. Phytother. Res., 2008, 22(9), 1175-1182.
[http://dx.doi.org/10.1002/ptr.2391] [PMID: 18729252]
[107]
Park, D.H.; Shin, J.W.; Park, S.K.; Seo, J.N.; Li, L.; Jang, J.J.; Lee, M.J. Diethylnitrosamine (DEN) induces irreversible hepatocellular carcinogenesis through overexpression of G1/S-phase regulatory proteins in rat. Toxicol. Lett., 2009, 191(2-3), 321-326.
[http://dx.doi.org/10.1016/j.toxlet.2009.09.016] [PMID: 19822196]
[108]
Tolba, R.; Kraus, T.; Liedtke, C.; Schwarz, M.; Weiskirchen, R. Diethylnitrosamine (DEN)-induced carcinogenic liver injury in mice. Lab. Anim., 2015, 49(1)(Suppl.), 59-69.
[http://dx.doi.org/10.1177/0023677215570086] [PMID: 25835739]
[109]
Magesh, V.; Singh, J.P.; Selvendiran, K.; Ekambaram, G.; Sakthisekaran, D. Antitumour activity of crocetin in accordance to tumor incidence, antioxidant status, drug metabolizing enzymes and histopathological studies. Mol. Cell. Biochem., 2006, 287(1-2), 127-135.
[http://dx.doi.org/10.1007/s11010-005-9088-0] [PMID: 16685462]
[110]
Tseng, T.H.; Chu, C.Y.; Huang, J.M.; Shiow, S.J.; Wang, C.J. Crocetin protects against oxidative damage in rat primary hepatocytes. Cancer Lett., 1995, 97(1), 61-67.
[http://dx.doi.org/10.1016/0304-3835(95)03964-X] [PMID: 7585479]
[111]
Abu-Rizq, H.A.; Mansour, M.H.; Safer, A.M.; Afzal, M. Cyto-protective and immunomodulating effect of Curcuma longa in Wistar rats subjected to carbon tetrachloride-induced oxidative stress. Inflammopharmacology, 2008, 16(2), 87-95.
[http://dx.doi.org/10.1007/s10787-007-1621-1] [PMID: 18340409]
[112]
Adetoro, K.O.; Bolanle, J.D.; Abdullahi, S.B.; Ahmed, O.A. In vivo antioxidant effect of aqueous root bark, stem bark and leaves extracts of Vitex doniana in CCl4 induced liver damage rats. Asian Pac. J. Trop. Biomed., 2013, 3(5), 395-400.
[http://dx.doi.org/10.1016/S2221-1691(13)60083-0] [PMID: 23646304]
[113]
Ahn, T.H.; Yang, Y.S.; Lee, J.C.; Moon, C.J.; Kim, S.H.; Jun, W.; Park, S.C.; Kim, J.C. Ameliorative effects of pycnogenol on carbon tetrachloride-induced hepatic oxidative damage in rats. Phytother. Res., 2007, 21(11), 1015-1019.
[http://dx.doi.org/10.1002/ptr.2146] [PMID: 17886222]
[114]
Al-Harbi, N.O.; Imam, F.; Nadeem, A.; Al-Harbi, M.M.; Iqbal, M.; Ahmad, S.F. Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin. Int. Immunopharmacol., 2014, 21(2), 383-388.
[http://dx.doi.org/10.1016/j.intimp.2014.05.014] [PMID: 24874442]
[115]
Ritesh, K.R.; Suganya, A.; Dileepkumar, H.V.; Rajashekar, Y.; Shivanandappa, T. A single acute hepatotoxic dose of CCl4 causes oxidative stress in the rat brain. Toxicol. Rep., 2015, 2, 891-895.
[http://dx.doi.org/10.1016/j.toxrep.2015.05.012] [PMID: 28962426]
[116]
Al-Yahya, M.; Mothana, R.; Al-Said, M.; Al-Dosari, M.; Al-Musayeib, N.; Al-Sohaibani, M.; Parvez, M.K.; Rafatullah, S. Attenuation of ccl4-induced oxidative stress and hepatonephrotoxicity by saudi sidr honey in rats. Evid. Based Complement. Alternat. Med., 2013, 2013569037
[http://dx.doi.org/10.1155/2013/569037] [PMID: 23533498]
[117]
Balakumar, P.; Rohilla, A.; Thangathirupathi, A. Gentamicin-induced nephrotoxicity: Do we have a promising therapeutic approach to blunt it? Pharmacol. Res., 2010, 62(3), 179-186.
[http://dx.doi.org/10.1016/j.phrs.2010.04.004] [PMID: 20434560]
[118]
Lopez-Novoa, J.M.; Quiros, Y.; Vicente, L.; Morales, A.I.; Lopez-Hernandez, F.J. New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int., 2011, 79(1), 33-45.
[http://dx.doi.org/10.1038/ki.2010.337] [PMID: 20861826]
[119]
Randjelovic, P.; Veljkovic, S.; Stojiljkovic, N.; Sokolovic, D.; Ilic, I. Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI J., 2017, 16, 388-399.
[PMID: 28507482]
[120]
Boroushaki, M.T.; Sadeghnia, H.R. Protective effect of safranal against gentamicin-induced nephrotoxicity in rat. Iran. J. Med. Sci., 2015, 34(4), 285-288.
[121]
Yarijani, Z.M.; Najafi, H.; Hamid Madani, S. Protective effect of crocin on gentamicin-induced nephrotoxicity in rats. Iran. J. Basic Med. Sci., 2016, 19(3), 337-343.
[PMID: 27114805]
[122]
el Daly, E.S. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J. Pharm. Belg., 1998, 53(2), 87-93.
[PMID: 9609969]
[123]
Naghizadeh, B.; Boroushaki, M.T.; Vahdati Mashhadian, N.; Mansouri, M.T. Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats. Iran. Biomed. J., 2008, 12(2), 93-100.
[PMID: 18506215]
[124]
Naghizadeh, B.; Mansouri, S.M.; Mashhadian, N.V. Crocin attenuates cisplatin-induced renal oxidative stress in rats. Food Chem. Toxicol., 2010, 48(10), 2650-2655.
[http://dx.doi.org/10.1016/j.fct.2010.06.035] [PMID: 20600529]
[125]
Karafakıoğlu, Y.S.; Bozkurt, M.F.; Hazman, Ö.; Fıdan, A.F. Efficacy of safranal to cisplatin-induced nephrotoxicity. Biochem. J., 2017, 474(7), 1195-1203.
[http://dx.doi.org/10.1042/BCJ20160971] [PMID: 28188255]
[126]
Krohn, K. Interaction of natural and synthetic anthracyclines with DNA (supporting material). Curr. Bioact. Compd., 2008, 4(3), 175-188.
[http://dx.doi.org/10.2174/157340708786305943]
[127]
Ghigo, A.; Li, M.; Hirsch, E. New signal transduction paradigms in anthracycline-induced cardiotoxicity. Biochim. Biophys. Acta, 2016, 1863(7 Pt B), 1916-1925.
[http://dx.doi.org/10.1016/j.bbamcr.2016.01.021] [PMID: 26828775]
[128]
Ichikawa, Y.; Ghanefar, M.; Bayeva, M.; Wu, R.; Khechaduri, A.; Naga Prasad, S.V.; Mutharasan, R.K.; Naik, T.J.; Ardehali, H. Cardiotoxicity of doxorubicin is mediated through mitochondrial iron accumulation. J. Clin. Invest., 2014, 124(2), 617-630.
[http://dx.doi.org/10.1172/JCI72931] [PMID: 24382354]
[129]
Mitry, M.A.; Edwards, J.G. Doxorubicin induced heart failure: Phenotype and molecular mechanisms. Int. J. Cardiol. Heart Vasc., 2016, 10, 17-24.
[http://dx.doi.org/10.1016/j.ijcha.2015.11.004] [PMID: 27213178]
[130]
Octavia, Y.; Tocchetti, C.G.; Gabrielson, K.L.; Janssens, S.; Crijns, H.J.; Moens, A.L. Doxorubicin-induced cardiomyopathy: from molecular mechanisms to therapeutic strategies. J. Mol. Cell. Cardiol., 2012, 52(6), 1213-1225.
[http://dx.doi.org/10.1016/j.yjmcc.2012.03.006] [PMID: 22465037]
[131]
Potnuri, A.G.; Kondru, S.K.; Samudrala, P.K.; Allakonda, L. Prevention of adriamycin induced cardiotoxicity in rats-a comparative study with subacute angiotensin-converting enzyme inhibitor and nonselective beta blocker therapy. IJC Metab. Endocr., 2017, 14, 59-64.
[http://dx.doi.org/10.1016/j.ijcme.2017.01.001]
[132]
Torres, V.M.; Simic, V.D. Doxorubicin-induced oxidative injury of cardiomyocytes-do we have right strategies for prevention? Cardiotoxicity of oncologic treatments; Fiuza, M., Ed.; In- TechOpen: London, , 2012. Vol. 1, pp. 90-116
[133]
Volkova, M.; Russell, R., III Anthracycline cardiotoxicity: prevalence, pathogenesis and treatment. Curr. Cardiol. Rev., 2011, 7(4), 214-220.
[http://dx.doi.org/10.2174/157340311799960645] [PMID: 22758622]
[134]
Zhang, S.; Liu, X.; Bawa-Khalfe, T.; Lu, L.S.; Lyu, Y.L.; Liu, L.F.; Yeh, E.T. Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat. Med., 2012, 18(11), 1639-1642.
[http://dx.doi.org/10.1038/nm.2919] [PMID: 23104132]
[135]
Razmaraii, N.; Babaei, H.; Mohajjel Nayebi, A.; Assadnassab, G.; Ashrafi Helan, J.; Azarmi, Y. Crocin treatment prevents doxorubicin-induced cardiotoxicity in rats. Life Sci., 2016, 157, 145-151.
[http://dx.doi.org/10.1016/j.lfs.2016.06.012] [PMID: 27297631]
[136]
Chahine, N.; Hanna, J.; Makhlouf, H.; Duca, L.; Martiny, L.; Chahine, R. Protective effect of saffron extract against doxorubicin cardiotoxicity in isolated rabbit heart. Pharm. Biol., 2013, 51(12), 1564-1571.
[http://dx.doi.org/10.3109/13880209.2013.802812] [PMID: 24003974]
[137]
Chahine, N.; Makhlouf, H.; Duca, L.; Martiny, L.; Chahine, R. Cardioprotective effect of saffron extracts against acute doxorubicin toxicity in isolated rabbit hearts submitted to ischemia-reperfusion injury. Z. Natforsch. C J. Biosci., 2014, 69(11-12), 459-470.
[http://dx.doi.org/10.5560/znc.2014-0124] [PMID: 25854766]
[138]
Chahine, N.; Nader, M.; Duca, L.; Martiny, L.; Chahine, R. Saffron extracts alleviate cardiomyocytes injury induced by doxorubicin and ischemia-reperfusion in vitro. Drug Chem. Toxicol., 2016, 39(1), 87-96.
[http://dx.doi.org/10.3109/01480545.2015.1036281] [PMID: 25885550]

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