Antioxidant and genoprotective effects of osthole against cadmium-induced DNA damage: an in vitro study using comet assay

Ehsan Vahidifar , Seyed Ebrahim Sajjadi, Mahmoud Etebari

Abstract


Background and purpose: Osthole, a plant-derived coumarin, has shown numerous pharmacological effects. However, its genoprotective effects against cadmium-induced DNA damage have not been determined yet. Therefore, this project aimed to assess the effectiveness of osthole against genotoxicity caused by cadmium.

Experimental approach: For this purpose, human umbilical vein endothelial cells (HUVECs) were incubated with various concentrations of osthole (40, 60, 80, and 120 µM) 24 h before cadmium chloride (CdCl2) treatment (40 µM), and then DNA damage was evaluated by comet assay. Furthermore, DPPH and                             free thiol group assays were applied to evaluate reactive oxygen species scavenger and antioxidant capacities of osthole.

Findings / Results: In the present study, all concentrations of osthole significantly decreased CdCl2-induced DNA damage. Furthermore, the antioxidant properties of the osthole were confirmed by DPPH and free thiol assays.

Conclusion and implications: Overall, the findings of this project revealed that osthole could ameliorate cadmium-induced genotoxicity probably by its antioxidant activity.

Keywords


Cadmium; Comet assay; DNA damage; Genotoxicity, Osthole; Oxidative stress.

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References


Filipič M, Hei TK. Mutagenicity of cadmium in mammalian cells: implication of oxidative DNA damage. Mutat Res. 2004;546(1-2):81-91. DOI: 10.1016/j.mrfmmm.2003.11.006.

Chomchan R, Siripongvutikorn S, Maliyam P, Saibandith B, Puttarak P. Protective Effect of Selenium-Enriched Ricegrass Juice against Cadmium-Induced Toxicity and DNA Damage in HEK293 Kidney Cells. Foods. 2018;7(6):81-94. DOI: 10.3390/foods7060081.

Sahmoun AE, Case LD, Jackson SA, Schwartz GG. Cadmium and prostate cancer: a critical epidemiologic analysis. Cancer Invest. 2005;23(3):256-263.DOI: 10.1081/CNV-200055968.

Joseph P. Mechanisms of cadmium carcinogenesis. Toxicol Appl Pharmacol. 2009;238(3):272-279.DOI: 10.1016/j.taap.2009.01.011.

Zhang H, Reynolds M. Cadmium exposure in living organisms: A short review. Sci Total Environ. 2019;678:761-767.DOI: 10.1016/j.scitotenv.2019.04.395.

Dai Z, Cheng J, Bao L, Zhu X, Li H, Chen X, et al. Exposure to waterborne cadmium induce oxidative stress, autophagy and mitochondrial dysfunction in the liver of Procypris merus. Ecotoxicol Environ Saf. 2020;204:111051,1-7.DOI: 10.1016/j.ecoenv.2020.111051.

Đukić-Ćosić D, Baralić K, Javorac D, Djordjevic AB, Bulat Z. An overview of molecular mechanisms in cadmium toxicity. Curr Opin Toxicol. 2020;19:56-62.DOI: 10.1016/j.cotox.2019.12.002.

Ataei N, Aghaei M, Panjehpour M. The protective role of melatonin in cadmium-induced proliferation of ovarian cancer cells. Res Pharm Sci. 2018;13(2):159-167.DOI: 10.4103/1735-5362.223801.

Cheng C-H, Ma H-L, Deng Y-Q, Feng J, Jie Y-K, Guo Z-X. Oxidative stress, cell cycle arrest, DNA damage and apoptosis in the mud crab (Scylla paramamosain) induced by cadmium exposure. Chemosphere. 2021;263:128277,1-11.DOI: 10.1016/j.chemosphere.2020.128277

Schwerdtle T, Ebert F, Thuy C, Richter C, Mullenders LHF, Hartwig A. Genotoxicity of soluble and particulate cadmium compounds: impact on oxidative DNA damage and nucleotide excision repair. Chem Res Toxicol. 2010;23(2):432-442.DOI: 10.1021/tx900444w.

Waalkes MP. Cadmium carcinogenesis in review. J Inorg Biochem. 2000;79(1-4):241-244.DOI: 10.1016/S0162-0134(00)00009-X.

Che Y, Li J, Li Z, Li J, Wang S, Yan Y, et al. Osthole enhances antitumor activity and irradiation sensitivity of cervical cancer cells by suppressing ATM/NF‑κB signaling. Oncol Rep. 2018;40(2):737-747.DOI: 10.3892/or.2018.6514.

Sadraei H, Shokoohinia Y, Sajjadi SE, Ghadirian B. Antispasmodic effect of osthole and Prangos ferulacea extract on rat uterus smooth muscle motility. Res Pharm Sci. 2012;7(3):141-149.PMID: 23181092.

Zafar S, Sarfraz I, Rasul A, Shah MA, Hussain G, Zahoor MK, et al. Osthole: A multifunctional natural compound with potential anticancer, antioxidant and anti-inflammatory Activities. Mini Rev Med Chem. 2021;21(18):2747-2763.DOI: 10.2174/1389557520666200709175948.

Ji H-J, Hu J-F, Wang Y-H, Chen X-Y, Zhou R, Chen N-H. Osthole improves chronic cerebral hypoperfusion induced cognitive deficits and neuronal damage in hippocampus. Eur J Pharmacol. 2010;636(1-3):96-101.DOI: 10.1016/j.ejphar.2010.03.038.

Mobarakeh K, Etebari M, Zolfaghari B, Jafarian-Dehkordi A. Evaluation of genoprotective effects of hydroalcoholic and polyphenolic extracts of Quince by comet assay. J Rep Pharm Sci. 2015;4(2):155-161.

Nasiri M, Etebari M, Jafarian-Dehkordi A, Moradi S. Lovastatin prevents bleomycin-induced DNA damage to HepG2 cells. Res Pharm Sci. 2016;11(6):470-475. DOI: 10.4103/1735-5362.194876.

Ghassemi-Barghi N, Varshosaz J, Etebari M, Jafarian Dehkordi A. Role of recombinant human erythropoietin loading chitosan-tripolyphosphate nanoparticles in busulfan-induced genotoxicity: analysis of DNA fragmentation via comet assay in cultured HepG2 cells. Toxicol In Vitro. 2016; 36:46-52.DOI: 10.1016/j.tiv.2016.07.001.

Sharifan A, Etebari M, Zolfaghari B, Aliomrani M. Investigating the effects of bark extract and volatile oil of Pinus eldarica against cisplatin-induced genotoxicity on HUVECs cell line. Toxicol Res. 2021;10(2):354-367.DOI: 10.1093/toxres/tfab006.

Zhang Z-R, Leung WN, Cheung HY, Chan CW. Osthole: a review on its bioactivities, pharmacological properties, and potential as alternative medicine. Evid Based Complement Alternat Med. 2015;2015:919616,1-10.DOI: 10.1155/2015/919616.

Çatav ŞS, Genç TO, Oktay MK, Küçükakyüz K. Cadmium toxicity in wheat: impacts on element contents, antioxidant enzyme activities, oxidative stress, and genotoxicity. Bull Environ Contam Toxicol. 2020;104(1):71-77.DOI: 10.1007/s00128-019-02745-4

Nouairi I, Jalali K, Essid S, Zribi K, Mhadhbi H. Alleviation of cadmium-induced genotoxicity and cytotoxicity by calcium chloride in faba bean (Vicia faba L. var. minor) roots. Physiol Mol Biol Plants. 2019;25(4):921-931.DOI: 10.1007/s12298-019-00681-5.

Rozgaj R, Kasuba V, Fucic A. Genotoxicity of cadmium chloride in human lymphocytes evaluated by the comet assay and cytogenetic tests. J Trace Elem Med Biol. 2002;16(3):187-192.DOI:10.1016/S0946-672X(02)80024-4.DOI: 10.1016/j.toxlet.2018.12.014.

Badr GM, Elsawy H, Sedky A, Eid R, Ali A, Abdallah BM, et al. Protective effects of quercetin supplementation against short-term toxicity of cadmium-induced hematological impairment, hypothyroidism, and testicular disturbances in albino rats. Environ Sci Pollut Res. 2019;26(8):8202-8211.DOI: 10.1007/s11356-019-04276-1.

Aly FM, Kotb AM, Haridy MA, Hammad S. Impacts of fullerene C60 and virgin olive oil on cadmium-induced genotoxicity in rats. Sci Total Environ. 2018;630:750-756. DOI: 10.1016/j.scitotenv.2018.02.205.

Kasuba V, Rozgaj R. Micronucleus distribution in human peripheral blood lymphocytes treated in vitro with cadmium chloride in G0 and S phase of the cell cycle. Chemosphere. 2002;49(1):91-95.DOI: 10.1016/s0045-6535(02)00174-1.

Wang C-C, Yang M-L, Yang C-P, Liang C-H, Lee C-Y, Lin H-W, et al. Cadmium nitrate-induced cytotoxicity and genotoxicity via caspases in Neuro-2A neurons. Toxin Rev. 2018;37(1):39-43.DOI: 10.1080/15569543.2017.1313276.

Liu J, Qu W, Kadiiska MB. Role of oxidative stress in cadmium toxicity and carcinogenesis. Toxicol Appl Pharmacol. 2009;238(3):209-214.DOI: 10.1016/j.taap.2009.01.029.

Rizwan M, Ali S, Ali B, Adrees M, Arshad M, Hussain A, et al. Zinc and iron oxide nanoparticles improved the plant growth and reduced the oxidative stress and cadmium concentration in wheat. Chemosphere. 2019;214:269-277.DOI: 10.1016/j.chemosphere.2018.09.120.

Loix C, Huybrechts M, Vangronsveld J, Gielen M, Keunen E, Cuypers A. Reciprocal interactions between cadmium-induced cell wall responses and oxidative stress in plants. Front Plant Sci. 2017;8:1867-1868.DOI: 10.3389/fpls.2017.01867.

Cannan WJ, Pederson DS. Mechanisms and consequences of double-strand DNA break formation in chromatin. J Cell Physiol. 2016;231(1):3-14.DOI: 10.1002/jcp.25048.

Tao L, Gu X, Xu E, Ren S, Zhang L, Liu W, et al. Osthole protects against Ang II-induced endotheliocyte death by targeting NF-κB pathway and Keap-1/Nrf2 pathway. Am J Transl Res. 2019;11(1):142-159. PMID: 30787975.

Su J, Zhang F, Li X, Liu Z. Osthole promotes the suppressive effects of cisplatin on NRF2 expression to prevent drug-resistant cervical cancer progression. Biochem Biophys Res Commun. 2019;514(2):510-517.DOI: 10.1016/j.bbrc.2019.04.021.

Mousavi K, Niknahad H, Li H, Jia Z, Manthari RK, Zhao Y, et al. The activation of nuclear factor-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling blunts cholestasis-induced liver and kidney injury. Toxicol Res. 2021;10(4):911-927.DOI: 10.1093/toxres/tfab073.

Chu Q, Zhu Y, Cao T, Zhang Y, Chang Z, Liu Y, et al. Studies on the neuroprotection of osthole on glutamate-induced apoptotic cells and an Alzheimer’s disease mouse model via modulation oxidative stress. Appl Biochem Biotechnol. 2020;190(2):634-644.DOI: 10.1007/s12010-019-03101-2.

Yan Y-h, Li S-h, Li H-y, Lin Y, Yang J-x. Osthole protects bone marrow-derived neural stem cells from oxidative damage through PI3K/Akt-1 pathway. Neurochem Res. 2017;42(2):398-405.DOI: 10.1007/s11064-016-2082-y.

Liu W-B, Zhou J, Qu Y, Li X, Lu C-T, Xie K-L, et al. Neuroprotective effect of osthole on MPP+-induced cytotoxicity in PC12 cells via inhibition of mitochondrial dysfunction and ROS production. Neurochem Int. 2010;57(3):206-215.DOI: 10.1016/j.neuint.2010.05.011.

Lu Y, Liu Y, Yang C. Evaluating in vitro DNA damage using comet assay. J Vis Exp. 2017;(128):1-6.DOI: 10.3791/56450.


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