Crocin protects the liver and kidney from patulin-induced apoptosis in vivo
- 291 Downloads
Patulin (PAT) is a mycotoxin mainly produced by Aspergillus, Penicillium, and Bissochlamys. Given the high risk associated with this mycotoxin, its potential effects have been investigated by many studies. It is known to be teratogenic, mutagenic, and genotoxic, and it has been shown to induce damages in several organs in experimental animals. Our aim was to investigate the preventive effect against PAT-induced apoptosis in vivo using natural carotenoid, Crocin (CRO). Mice were divided into six groups: a control group, a “PAT alone” group, a “CRO alone” group, and a “PAT plus CRO” groups (pre-treatment conditions). Our results showed that CRO restored the normal levels of biochemical parameters in the liver and kidney. The analysis of the protein expression in these organs revealed that PAT-induced toxicity promotes the induction of apoptosis via the increase in P53, Bax, and cytochrome C and the decrease in Bcl2 expressions. We also found that PAT triggered caspase 3 activation and DNA fragmentation. However, pre-treatment with CRO demonstrated a reduction in the induction of apoptosis via the regulation of all tested biomarkers demonstrating that CRO is effective in the protection against PAT hazards. This could be relevant, particularly with the emergent demand for natural products which may counteract the detrimental toxic effects and therefore prevents multiple human diseases.
KeywordsPatulin Crocin P53 Caspase 3 Apoptosis DNA fragmentation
Gamma glutamyl transferase
This research was supported by the Ministère Tunisien de l’Enseignement Superieur et de la Recherche Scientifique et de la Technologie (Laboratoire de Recherche sur les Substances Biologiquement Compatibles, LRSBC). The authors are thankful to Mr. Hassen Bacha and Mr. Mohamed Fadhel Najjar for their laboratory supports and for their constructive suggestions during the course of study.
Compliance with ethical standards
All procedures were carried out in accordance with the National Institute of Health Guidelines for Animal Care and approved by the local ethics committee.
Conflict of interest
The authors declare that they have no competing interests.
- Boussabbeh M, Prola A, Ben Salem I, Guilbert A, Bacha H, Lemaire C, Abis-Essefi S. (2015b). Crocin and quercetin prevent PAT-induced apoptosis in mammalian cells: involvement of ROS-mediated ER stress pathway. Environ Toxicol. Aug 27. doi: 10.1002/tox.22185.
- Boussabbeh M, Ben Salem I, Belguesmi F, Bacha H, Abid-Essefi S. (2015c). Tissue oxidative stress induced by patulin and protective effect of crocin. Neurotoxicology. doi: 10.1016/j.neuro.2015.11.005
- Boussabbeh M, Ben Salem I, Neffati F, Najjar MF, Bacha H, Abid-Essefi S. (2015d) Crocin prevents patulin-induced acute toxicity in cardiac tissues via the regulation of oxidative damage and apoptosis. J Biochem Mol Toxicol. Jun 11. doi: 10.1002/jbt.21718.
- Burlinson B, Tice RR, Speit G, Agurell E, Brendler-Schwaab SY, Collins AR, Escobar P, Honma M, Kumaravel TS, Nakajima M, Sasaki YF, Thybaud V, Uno Y, Vasquez M, Hartmann A (2007) Fourth International Workgroup on Genotoxicity testing: results of the in vivo comet assay workgroup. Mutat Res 627:31–35CrossRefGoogle Scholar
- Ciegler A, Becwith AC, Jackson LK (1976) Teratogenicity of patulin and patulin adducts formed with cysteine. Appl Environ Microbiol 31:664–667Google Scholar
- De Melo FT, De Oliveira IM, Greggio S, Costa Dacosta J, Guecheva TN, Saffi J, Pêgas Henriques JA, Rosa RM (2012). DNA damage in organs of mice treated acutely with patulin, a known mycotoxin.Google Scholar
- EL-Maraghy SA, Rizk SM, El-Sawalhi MM (2009) Hepatoprotective potential of crocin and curcumin against iron overload-induced biochemical alterations in rat. Afr J Biochem Res 3:215–221Google Scholar
- Hayes AW, Phillips TD, Williams WL, Ciegler A (1979) Acute toxicity of patuline in mice and rats. Toxicology 13:91–100Google Scholar
- International Agency for Research on Cancer. (1968). Some naturally occurring and synthetic food components, furocoumarins and ultraviolet radiation. WHO. Available at: http://monographs.iarc.fr/ENG/Monographs/vol1-42/mono40.pdf
- Kianbakht S, Mozaffari K (2009) Effects of saffron and its active constituents, crocin and safranal, on prevention of indomethacin induced gastric ulcers in diabetic and nondiabetic rats. J Med Plants 8:30–38Google Scholar
- Mori H, Kawai K, Ohbayashi F, Kuniyasu T, Yamazaki M, Hamasaki T, Williams GM (1984) Genotoxicity of a variety of mycotoxins in the hepatocyte primary culture/DNA repair test using rat and mouse hepatocytes. Cancer Res 44:2918–2923Google Scholar
- Naghizadeh B, Boroushaki M, Vahdati MN, Mansouri M (2008) Protective effects of crocin against cisplatin-induced acute renal failure and oxidative stress in rats, Iran. Biomed J 12:93Google Scholar
- Roll R, Matthiaschk G, Korte A (1990) Embryotoxicity and mutagenicity of mycotoxins. J Environ Pathol Toxicol Oncol 10:1–7Google Scholar