Abstract
Saffron (Crocus sativus) is a widely used food additive for its color and taste. Crocin and safranal are two main components of this plant. Numerous studies are underway to introduce saffron and its active ingredients as pharmacological agents. Safety assessments of these compounds are important parts of this endeavor. In this study, the effects of crocin and safranal administrations during embryogenesis have been investigated in mice. A total of 75 BALB/c pregnant mice were divided into six experimental and control groups. Four experimental groups received intraperitoneal injection of crocin (200 mg/kg or 600 mg/kg) daily or safranal (0.075 ml/kg or 0.225 ml/kg) on gestational days (GDs) 6 to 15. Control groups received normal saline or paraffin as solvents of crocin and safranal. Dams were dissected on GD18 and embryos were collected. Routine maternal and fetal parameters were recorded. Macroscopic observation of external malformations was also performed. Fetuses were then selected for double skeletal staining with alizarin red and alcian blue. All experimental groups caused significant decrease in length and weight of fetuses when compared with the control groups and revealed malformations such as minor skeletal malformations, mandible and calvaria malformations, and growth retardation. Minor skeletal malformations were the most commonly observed abnormality, which were statistically significant when compared with the control groups (p < 0.05). The severities of malformations were comparable in the crocin- and safranal-treated groups. This study suggests that crocin or safranal can induce embryonic malformations when administered in pregnant mice. Due to the wide use of saffron, further elaborate studies to understand the malformation mechanisms of these ingredients are recommended.
| Abdullaev, FI, Espinosa-Aguirre, JJ (2004) Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detection and Prevention 28(6): 426–432. Google Scholar, Crossref, Medline | |
| Assimopoulou, AN, Sinakos, Z, Papageorgiou, VP (2005) Radical scavenging activity of Crocus sativus L. extract and its bioactive constituents. Phytotherapy Research 19(11): 997–1000. Google Scholar, Crossref, Medline, ISI | |
| Basheeruddin Asdaq, SM, Inamdar, MN (2010) Potential of Crocus sativus (saffron) and itsconstituent, crocin, as hypolipidemic and antioxidant in rats. Applied Biochemistry and Biotechnology 162: 358–372. Google Scholar, Crossref, Medline, ISI | |
| Dehghani, Z, Dehghani, S (2009) Effect of saffron on the increasing of abortion. In: International Symposium on Saffron: A Herbal Medicine of 3rd Millennium, May 13–14, Mashhad, Iran. Google Scholar | |
| Golalipour, MJ, Gharravi, AM, Ghafari, S, Afshar, M, Khori, V (2008) Effects of Crocus sativus on the fetal development of NMRI mice. Saudi Medical Journal 29(2): 309–310. Google Scholar, Medline, ISI | |
| Gout, BC, Bourges, C, Paineau-Dubreuil, S (2010) Satiereal, a Crocus sativus L. extract, reduces snacking and increases satiety in a randomized placebo-controlled study of mildly overweight, healthy women. Nutrition Research 30(5): 305–313. Google Scholar, Crossref, Medline, ISI | |
| Hosseinzadeh, H, Karimi, G, Niapoor, M (2004) Antidepressant effect of Crocus sativus L. Stigma extracts and their constituents, crocin and safranal, in mice. Acta Horticulturae 650: 435–445. Google Scholar, Crossref | |
| Hosseinzadeh, H, Nassiri-Asl, M (2013) Avicenna’s (IbnSina) the canon of medicine and saffron (Crocus sativus): a review. Phytotherapy Research 27: 475–483. Google Scholar, Crossref, Medline, ISI | |
| Hosseinzadeh, H, Sadeghnia, HR (2005). Safranal, a constituent of Crocus sativus (saffron), attenuated cerebral ischemia induced oxidative damage in rat hippocampus. Journal of Pharmacy and Pharmaceutical Sciences 8(3): 394–399. Google Scholar, Medline, ISI | |
| Hosseinzadeh, H, Sadeghnia, HR (2007) Protective effect of safranal on pentylenetetrazol-induced seizures in the rat: involvement of GABAergic and opioids systems. Phytomedicine 14(4): 256–262. Google Scholar, Crossref, Medline, ISI | |
| Hosseinzadeh, H, Talebzadeh, F (2005) Anticonvulsant evaluation of safranal and crocin from Crocus sativus in mice. Fitoterapia 76(7–8): 722–724. Google Scholar, Crossref, Medline, ISI | |
| Inouye, M (1976) Differential staining of cartilage and bone in fetal mouse skeletal by alcian blue and alizarin red s. Congenital Anomalies 16(3): 171–173. Google Scholar | |
| Kimmel, CA, Trammell, C (1981) A rapid procedure for routine double staining of cartilage and bone in fetal and adult animals. Stain Technology 56(5): 271–273. Google Scholar, Crossref, Medline | |
| Martin, G, Goh, E, Neff, AW (2002) Evaluation of the developmental toxicity of crocetin on Xenopus. Food and Chemical Toxicology 40(7): 959–964. Google Scholar, Crossref, Medline, ISI | |
| Moghaddasi, MS (2010) Saffron chemicals and medicine usage. Journal of Medicinal Plants Research 4(6): 427–430. Google Scholar | |
| Soeda, S, Ochiai, T, Shimeno, H, Saito, H, Abe, K, Tanaka, H. (2007) Pharmacological activities of crocin in saffron. Journal of Natural Medicines 61(2): 102–111. Google Scholar, Crossref, ISI | |
| Tafazoli, M, Kermani, T, Saadatjoo, A (2004) Effects of saffron on abortion and its side effects on mice Balb/c. Ofogh-e-Danesh 10(3): 53–56. Google Scholar | |
| Tian, Y, Ishikawa, H, Yamaguchi, T, Yamauchi, T, Yokoyama, K (2005) Teratogenicity and developmental toxicity of chlorpyrifos. Maternal exposure during organogenesis in mice. Reproductive Toxicology 20(2): 267–270. Google Scholar, Crossref, Medline, ISI | |
| Zheng, YQ, Liu, JX, Wang, JN, Xu, L (2007) Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Research 1138: 86–94. Google Scholar, Crossref, Medline, ISI | |
| Zougagh, MA, Rois, A, Valcarcel, M (2006) Determination of total safranal by in situ acid hydrolysis in supercritical fluid media: application to the quality control of commercial saffron. Analytica Chimica Acta 578(2): 117–121. Google Scholar, Crossref, Medline, ISI |

