Effect of crocin on PKHD1 and KLLN genes expression in kidney tissue of female rats treated with cadmium
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
The publication is free and its contents are distributed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International licence (CC BY-NC-ND 4.0). The rights of the works published in this journal are property of the author and they are free to distribute and disseminate the same sources as long as he correctly cites the font of publication, these acts are not for commercial purposes and no derivative works are generated.
Main Article Content
Abstract
According to data from studies, antioxidant herbal compounds are, likely to have a useful role in reducing the harmful effects of environmental pollutants and toxic chemicals that most people are exposed to. Cadmium is one of the toxic elements that accumulate in many organs, especially in kidneys. The aim of this study was to investigate the effect of crocin on the expression of PKHD1 and KLLN genes in cadmium-treated rats.
In this experimental study, 40 adults male Wistar rats (200-250 g) were randomly divided into the following groups: control group received normal saline, cadmium group (15mg/kg), crocin group (20mg/kg) and cadmium group daily fed with crocin at a dose of 20 mg/kg.
After eight weeks of treatment, rats were dissected, and kidney tissues were removed for evaluation of PKHD1 and KLLN gene expression by real time method. The data were analyzed using oneway ANOVA and significant difference between groups was P<0.05.
Our results showed an increase in PKHD1 gene expression and a decrease in KLLN gene expression in kidney tissue in the cadmium group compared to the control group (P <0.001). Also, a significant decrease in PKHD1 gene expression (P <0.001) and an increase in KLLN gene expression P <0.05) were observed in the tissues of all cadmium-treated rats compared to cadmium.
Crocin consumption can have a protective effect against the impaired expression of PKHD1 and KLLN cadmium-induced apoptotic pathway.
References
Amin, A., Bajbouj, K., Koch, A., Gandesiri, M., Schneider-Stock, R. (2017) Defective Autophagosome Formation in p53-Null Colorectal Cancer Reinforces Crocin-Induced Apoptosis. Int J Mol Sci. , 16(1):1544-1561. https://doi.org/10.3390/ijms16011544
Bakhtiary, Z., Shahrooz, R., Ahmadi, A., Malekinejad, H., Mostafavi, M. (2014) Study of protevtive effects of crocin on testicular histomorphometry and serological parameters in cyclophosphamide on treated adulte mice. Stud Med Sci., 25(7):663-673. URL: http://umj.umsu.ac.ir/article-1-2417-en.html
Bakshi, H.A., Hakkim, F.L., Sam, S., Javid, F., Rashan, L. (2017) Dietary Crocin Reverses Melanoma Metastasis . J Biomed Res.,32(1):39‐50. https://doi.org/10.7555/JBR.31.20160120
Bennett, K.L., Campbell, R., Ganapathi ,S., Zhou ,M.;Rini ,B., Ganapathi, R, el at. (2011) Germline and somatic DNA methylation and epigenetic regulation of KILLIN in renal cell carcinoma. Genes Chromosomes Cancer.,50(8):654-61. https://doi.org/10.1002/gcc.20887
Chen, C., Xun, P.,Nishijo ,M., He ,K. (2016) Cadmium exposure and risk of lung cancer: a meta-analysis of cohort and case-control studies among general and occupational populations. J Expo Sci Environ Epidemiol., 26 (5):437‐444. https://doi.org/10.1038/jes.2016.6
Chen, Sh., Zhao, Sh., Wang, X ., Zhang, L. , Jiang, E., Guet, Y . et al. (2015) Crocin inhibits cell proliferation and enhances cisplatin and pemetrexed chemosensitivity in lung cancer cells. Transl Lung Cancer Res., 4(6): 775-783. https://doi.org/10.3978/j.issn.2218-6751.2015.11.03
Chen, Y.Y., Zhu, J.Y., Chan, K.M. (2014) Effects of cadmium on cell proliferation, apoptosis, and proto-oncogene expression in zebrafish liver cells. Aquat Toxicol.,157:196‐206. https://doi.org/10.1016/j.aquatox.2014.10.018
Chow ,W.H., Dong, L.M., Devesa ,S.S. (2010) Epidemiology and risk factors for kidney cancer. Nat Rev Urol.,7(5):245‐257. https://dx.doi.org/10.1038%2Fnrurol.2010.46
Ghotbeddin, Z.,Fatemi-Tabatabaei, S.R.,Tabandeh, M.R., Mirzabeigi, M., Badripour, N., Amiri R. (2017) Effect of crocin on inhibitory avoidance memory, balance and explorative behaviours following cisplatin administration in rat.Feyz.,21(2):118-25. https://doi.org/10.3390/ijms16011544
Hartwig, A., Schwerdtle, T. (2002) Interactions by carcinogenic metal compounds with DNA repair processes: toxicological implications. Toxicol Lett.,127(1-3):47‐54. https://doi.org/10.1016/S0378-4274(01)00482-9
Hoshyar, R.; Mollaei ,H. (2017) A comprehensive review on anticancer mechanisms of the main carotenoid of saffron, crocin. J Pharm Pharmacol.,69(11):1419‐1427. https://doi.org/10.1111/jphp.12776
Liu, T., He, W., Yan, C., Qi, Y., Zhang, Y. (2011). Roles of reactive oxygen species and mitochondria in cadmium-induced injury of liver cells. Toxicol Ind Health.,27(3):249-56. https://doi.org/10.1177/0748233710386408
Jalili, C., Salahshoor, M.R.,Moradi, M.T., Ahookhash, M., Taghadosi, M., Sohrabi, M. (2017) Expression Changes of Apoptotic Genes in Tissues from Mice Exposed to Nicotine. Asian Pac J Cancer Prev.,18(1):239‐244. https://doi.org/10.22034/apjcp.2017.18.1.239
Kilic, S., Kilic, M. (2017) Effects of cadmium-induced stress on essential oil production, morphology and physiology of lemon balm (Melissa officinalis L., Lamiaceae). Appl Ecol Environ Res., 15(3):1653-69. http://dx.doi.org/10.15666/aeer/1503_16531669
Kim, J.,Song, H., Heo, H.R., Kim, J.W., Kim, H.R., Hong ,Y.,et al. (2017) Cadmium-induced ER stress and inflammation are mediated through C/EBP-DDIT3 signaling in human bronchial epithelial cells. Exp Mol Med.,49(9):e372. https://doi.org/10.1038/emm.2017.125
Song, KJ., Luo, H., Yin, Xh., lei Huang, G., yang Luo ,S., Yuan ,D.B.,et al. (2015) Association between cadmium exposure and renal cancer risk: a meta-analysis of observational studies. Sci rep,5:17976. https://doi.org/10.1038/srep17976
Mahdavi, L.S .,Khodarahmi, P .,Hayati, R.N .(2017)Effects of intraperitoneal administration of cadmium on apoptotic bcl-2 and Bax genes expression in rat hippocampal cells. MGj.,12 (1) :81-89. http://mg.genetics.ir/browse.php?a_id=1470&sid=1&slc_lang=en
Mollaei, H., Safaralizadeh, R., Babaei, E., Abedini, M.R., Hoshyar, R.(2017) The anti-proliferative and apoptotic effects of crocin on chemosensitive and chemoresistant cervical cancer cells. Biomed Pharmacother.,94:307-316. https://doi.org/10.1016/j.biopha.2017.07.052
Nizialek ,E.A., Peterson, C., Mester, J.L., Downes-Kelly, E.; Eng, C. (2013) Germline and somatic KLLN alterations in breast cancer dysregulate G2 arrest. Hum Mol Genet.,22(12):2451‐2461. https://doi.org/10.1093/hmg/ddt097
Sá, I., Semedo, M., Cunha, M.E. (2016) Kidney cancer. Heavy metals as a risk factor. Porto Biomed J.,1(1):25‐28. https://doi.org/10.1016/j.pbj.2016.03.006
Siegel, R.L., Miller, K.D., Jemal ,A.(2016) Cancer statistics. CA Cancer J Clin.,66(1):7‐30. https://doi.org/10.3322/caac.21332
Sjöblom, T.,Jones, S.,Wood, L.D., Parsons, D.W., Lin ,J., Barber, T.D.,et al. (2006) The consensus coding sequences of human breast and colorectal cancers. Science.,314(5797):268-274. https://doi.org/10.1126/science.1133427
Wang, J., Ke ,Y., Shu, T.(2009) Crocin has pharmacological effects against the pathological behavior of colon cancer cells by interacting with the STAT3 signaling pathway. Exp Ther Med. 2020;19(2):1297-1303. doi:10.3892/etm.2019.8329Thévenod, F.Cadmium and cellular signaling cascades: to be or not to be?. Toxicol Appl Pharmacol.,238(3):221‐239. https://doi.org/10.1016/j.taap.2009.01.013
Thompson, E.R., Gorringe, K.L., Choong, D.Y., Eccles ,D.M., kConFab, Mitchell, G.,et al. (2012) Analysis of KLLN as a high-penetrance breast cancer predisposition gene. Breast Cancer Res Treat.,134(2):543-547. https://doi.org/10.1007/s10549-012-2088-3
Venza, M., Visalli, M., Biondo, C.,Oteri, R., Agliano, F., Morabito, S., et al. (2014) Epigenetic effects of cadmium in cancer: focus on melanoma. Curr Genomics.,15(6):420‐435. https://doi.org/10.2174/138920291506150106145932
Wang, Y., He, X., Yu, Q.,Eng ,C. (2013) Androgen receptor-induced tumor suppressor, KLLN, inhibits breast cancer growth and transcriptionally activates p53/p73-mediated apoptosis in breast carcinomas. Hum Mol Genet.,22(11):2263‐2272. https://doi.org/10.1093/hmg/ddt077
Ward, C.J.; Hogan, M.C.; Rossetti, S.; Walker, D.; Sneddon, T.; Wang ,X.;et al . (2002) The gene mutated in autosomal recessive polycystic kidney disease encodes a large, receptor-like protein. Nat Genet .,30(3):259-269. https://doi.org/10.1038/ng833
Ward, C.J., Wu ,Y., Johnson, R.A., Woollard, J.R., Bergstralh ,E.J.,Cicek, M.S.,et al. (2011) Germline PKHD1 mutations are protective against colorectal cancer. Hum Genet.,129(3):345-349. https://doi.org/10.1007/s00439-011-0950-8
Rafati Rahimzadeh, M., Rafati Rahimzadeh, M., Kazemi ,S., Moghadamnia, A.A.(2017) Cadmium toxicity and treatment: An update. Caspian J Intern Med. 8(3):135-145. https://doi.org/10.22088/cjim.8.3.135