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Acetylresveratrol as a Potential Substitute for Resveratrol Dragged the Toxic Aldehyde to Inhibit the Mutation of Mitochondrial DNA

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Abstract

The aim of this study was to explore whether or not acetylresveratrol as a potential substitute for resveratrol dragged the toxic aldehyde to inhibit the mutation of mitochondrial DNA. The results revealed that the acetylresveratrol shifted ultraviolet peak of trans-crotonaldehyde from 316 to 311 nm. In mitochondria, the acetylresveratrol split the ultraviolet peak at 311 nm of trans-crotonaldehyde into 311 nm and 309 nm; the aldehyde Raman band of trans-crotonaldehyde was red shifted by the acetylresveratrol from 1689 to 1686 cm−1 with obvious band decline; Raman bands at 1149 cm−1, 1168 cm−1, and 1325 cm−1 of acetylresveratrol disappeared. In aldehyde dehydrogenase, the aldehyde Raman band of trans-crotonaldehyde was red shifted by the acetylresveratrol from 1689 to 1684 cm−1 with band decline; Raman bands at 1150 cm−1, 1168 cm−1, and 1324 cm−1 of acetylresveratrol declined. The weak acidic microenvironment was the best, for the acetylresveratrol dragged the toxic aldehyde of trans-crotonaldehyde. Compared with the resveratrol, the effect of the acetylresveratrol on the toxic aldehyde of trans-crotonaldehyde was very similar to that of the resveratrol. The acetylresveratrol is very suitable as a potential substitute for resveratrol dragged the toxic aldehyde to inhibit the mutation of mitochondrial DNA.

In mitochondria, the Raman band of the toxic –CH=O of trans-crotonaldehyde (TCA) dragged by the Acetyl-Res from 1689 to 1686 cm−1 with obvious band decline, while the Raman bands at 1149 cm−1, 1168 cm−1, and 1325 cm−1 of the Acetyl-Res disappeared, respectively. The Acetyl-Res is very suitable as a potential substitute, for the Res dragged the toxic –CH=O of TCA to inhibit the mutation of mitochondrial DNA for anticancer.

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References

  1. Xue, Y. Q., Di, J. M., Luo, Y., Cheng, K. J., Wei, X., & Shi, Z. (2014). Resveratrol oligomers for the prevention and treatment of cancers. Oxidative Medicine and Cellular Longevity, 2014, 765832. https://doi.org/10.1155/2014/765832.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Walle, T., Hsieh, F., DeLegge, M. H., Oatis Jr., J. E., & Walle, U. K. (2004). High absorption but very low bioavailability of oral resveratrol in humans. Drug Metabolism and Disposition: The Biological Fate of Chemicals, 32, 1377. https://doi.org/10.1124/dmd.104.000885.

    Article  CAS  Google Scholar 

  3. Dobrydneva, Y., Williams, R. L., Morris, G. Z., & Blackmore, P. F. (2002). Dietary phytoestrogens and their synthetic structural analogues as calcium channel blockers in human platelets. Journal of Cardiovascular Pharmacology, 40, 399–410. https://doi.org/10.1097/00005344-200209000-00009.

    Article  CAS  PubMed  Google Scholar 

  4. Liang, L., Liu, X. Y., Wang, Q. W., Cheng, S. K., Zhang, S. Y., & Zhang, M. (2013). Pharmacokinetics, tissue distribution and excretion study of resveratrol and its prodrug 3,5,4′-tri-O-acetylresveratrol in rats. Phytomedicine, 20, 558–563. https://doi.org/10.1016/j.phymed.2012.12.012.

    Article  CAS  PubMed  Google Scholar 

  5. Wenzel, E., & Somoza, V. (2005). Metabolism and bioavailability of trans-resveratrol. Molecular Nutrition & Food Research, 49, 472–481. https://doi.org/10.1002/mnfr.200500010.

    Article  CAS  Google Scholar 

  6. Wenzel, E., Soldo, T., Erbersdobler, H., & Somoza, V. (2010). Bioactivity and metabolism of trans-resveratrol orally administered to Wistar rats. Molecular Nutrition & Food Research, 49, 482–494. https://doi.org/10.1002/mnfr.200500003.

    Article  CAS  Google Scholar 

  7. Lancon, A., Delmas, D., Osman, H., Thenot, J. P., Jannin, B., & Latruffe, N. (2014). Human hepatic cell uptake of resveratrol: involvement of both passive diffusion and carrier-mediated process. Biochemical and Biophysical Research Communications, 316, 1132–1137. https://doi.org/10.1016/j.bbrc.2004.02.164.

    Article  CAS  Google Scholar 

  8. Fragopoulou, E., Nomikos, T., Karantonis, H. C., Apostolakis, C., Pliakis, E., Samiotaki, M., Panayotou, G., & Antonopoulou, S. (2007). Biological activity of acetylated phenolic compounds. Journal of Agricultural and Food Chemistry, 55(1), 80–89. https://doi.org/10.1021/jf0627221.

    Article  CAS  PubMed  Google Scholar 

  9. Koide, K., Osman, S., Garner, A. L., Song, F., Dixon, T., Greenberger, J. S., & Epperly, M. W. (2011). The use of 3, 5, 4′-tri-O-acetylresveratrol as a potential prodrug for resveratrol protects mice from γ-irradiation-induced death. ACS Medicinal Chemistry Letters, 2, 270–274. https://doi.org/10.1021/ml100159p.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chan, A.S.C., Chen, S.L., Li, Y., & Yang, D. (2004) Puerarin derivatives and their medical uses. Google Patents.

  11. O’Brien, P. J., Siraki, A. G., & Shangari, N. (2005). Aldehyde sources, metabolism, molecular toxicity mechanisms, and possible effects on human health. Critical Reviews in Toxicology, 35, 609–662. https://doi.org/10.1080/10408440591002183.

    Article  CAS  PubMed  Google Scholar 

  12. Starkov, A., & A. (2008). The role of mitochondria in reactive oxygen species metabolism and signaling. Annals of the New York Academy of Sciences, 1147, 37–52. https://doi.org/10.1196/annals.1427.015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Kawanishi, M., Matsuda, T., Sasaki, G., & Takebe, H. (1998). A spectrum of mutations induced by croton aldehyde in shuttle vector plasmids propagated in human cells. Carcinogenesis, 19, 69–72. https://doi.org/10.1093/carcin/19.1.690.

    Article  CAS  PubMed  Google Scholar 

  14. Szczesny, B., Módis, K., Yanagi, K., & Szabo, C. (2014). AP39, a novel mitochondria-targeted hydrogen sulfide donor, stimulates cellular bioenergetics, exerts cytoprotective effects and protects against the loss of mitochondrial DNA integrity in oxidatively stressed endothelial cells in vitro. Nitric Oxide, 41, 120–130. https://doi.org/10.1016/j.niox.2014.04.008.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Williams, M. V., Lee, S. H., Pollack, M., & Blair, I. A. (2006). Endogenous lipid hydroperoxide-mediated DNA-adduct formation in min mice. The Journal of Biological Chemistry, 281, 10127–10133. https://doi.org/10.1074/jbc.M600178200.

    Article  CAS  PubMed  Google Scholar 

  16. Minko, I. G., Kozekov, I. D., Harris, T. M., Rizzo, C. J., Lloyd, R. S., & Stone, M. P. (2009). Chemistry and biology of DNA containing 1, N(2)-deoxyguanosine adducts of the α, β-unsaturated aldehydes acrolein, crotonaldehyde, and 4-hydroxynonenal. Chemical Research in Toxicology, 22, 759–778. https://doi.org/10.1021/tx9000489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Su, Y. B., Chen, L., Su, Y. W., Li, Z. Q., Zhang, C., & Mu, T. X. (2017). Spectroscopic evidences of toxic trans-crotonaldehyde trapped and transformed by resveratrol to prevent the damage of mitochondrial DNA. IUBMB Life, 69(7), 500–509. https://doi.org/10.1002/iub.1631.

    Article  CAS  PubMed  Google Scholar 

  18. Facecchia, K., Fochesato, L. A., Ray, S. D., Stohs, S. J., & Pandey, S. (2011, 2011). Oxidative toxicity in neurodegenerative diseases: role of mitochondrial dysfunction and therapeutic strategies. Journal of Toxicology, 1–12. https://doi.org/10.1155/2011/683728.

  19. Su, Y. B., Ma, X. W., Su, Y. W., Mu, T. X., Li, Y. H., Jiang, N., Su, Y. Y., & Zhang, Q. (2017). Influences of ethanol on the structure of toxic trans-crotonaldehyde in mitochondria coming from rat myocardium. Scientific Reports, 7(1), 10081. https://doi.org/10.1038/s41598-017-09656-6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Durig, J., Brown, S., Kalasinsky, V., & George, W. (1976). Low-frequency vibration of crotonaldehyde. Spectrochimica Acta Part A: Molecular Spectroscopy, 32, 807–813. https://doi.org/10.1016/0584-8539(76)80149-3.

    Article  Google Scholar 

  21. Jayaprakash, A., Arjunan, V., Jose, S. P., & Mohan, S. (2011). Spectrochim, vibrational and electronic investigations, thermodynamic parameters, HOMO and LUMO analysis on crotonaldehyde by ab initio and DFT methods. Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy, 83(1), 411–419. https://doi.org/10.1016/j.saa.2011.08.054.

    Article  CAS  PubMed  Google Scholar 

  22. Vongsvivut, J., Robertson, E. G., & McNaughton, D. (2008). Surface-enhanced Raman scattering spectroscopy of resveratrol. Australian Journal of Chemistry, 61, 921–929. https://doi.org/10.1071/CH082040004-9425/08/120921.

    Article  CAS  Google Scholar 

  23. Billes, F., Mohammed–Ziegler, I., Mikosch, H., & Tyihak, E. (2007). Vibrational spectroscopy of resveratrol. Spectrochimica Acta A, 68, 669–679. https://doi.org/10.1016/j.saa.2006.12.045.

    Article  CAS  Google Scholar 

  24. Ohno, M., Sakumi, K., Fukumura, R., Furuichi, M., Iwasaki, Y., Hokama, M., Ikemura, T., Tsuzuki, T., Gondo, Y., & Nakabeppu, Y. (2014). 8-oxoguanine causes spontaneous de novo germline mutations in mice. Scientific Reports, 4, 4689. https://doi.org/10.1038/srep04689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Churchill, E. N., Disatnik, M. H., & Mochly-Rosen, D. (2009). Time-dependent and ethanol-induced cardiac protection from ischemia mediated by mitochondrial translocation of εPKC and activation of aldehyde dehydrogenase 2. Journal of Molecular and Cellular Cardiology, 46, 278–284. https://doi.org/10.1016/j.yjmcc.2008.09.713.

    Article  CAS  PubMed  Google Scholar 

  26. Jackson, B., Brocker, C., Thompson, D. C., Black, W., Vasiliou, K., Nebert, D. W., & Vasiliou, V. (2011). Update on the aldehyde dehydrogenase gene (ALDH) superfamily. Human Genomics, 5(4), 283–303. https://doi.org/10.1186/1479-7364-5-4-283.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Marchitti, S. A., Brocker, C., Stagos, D., & Vasiliou, V. (2008). Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily. Expert Opinion on Drug Metabolism & Toxicology, 4(6), 697–720. https://doi.org/10.1517/17425255.4.6.697.

    Article  CAS  Google Scholar 

  28. Yip, N. C., Fombon, I. S., Liu, P., Brown, S., Kannappan, V., Armesilla, A. L., Xu, B., Cassidy, J., Darling, J. L., & Wang, W. (2011). Disulfiram modulated ROS–MAPK and NFkappaB pathways and targeted breast cancer cells with cancer stem cell-like properties. British Journal of Cancer, 104, 1564–1574. https://doi.org/10.1038/bjc.2011.126.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Grune, T. (2014). Protein oxidation products as biomarkers. Free Radical Biology & Medicine, 75, S7. https://doi.org/10.1016/j.freeradbiomed.2014.10.843.

    Article  Google Scholar 

  30. Rodríguez-Zavala, J. S., Calleja, L. F., Moreno-Sánchez, R., & Yoval-Sánchez, B. (2019). Role of aldehyde dehydrogenases in physiopathological processes. Chemical Research in Toxicology, 32, 405–420. https://doi.org/10.1021/acs.chemrestox.8b00256.

    Article  CAS  PubMed  Google Scholar 

  31. Feron, V. J., Til, H. P., de Vrijer, F., Woutersen, R. A., Cassee, F. R., & van Bladeren, P. J. (1991). Aldehydes: occurrence, carcinogenic potential, mechanism of action and risk assessment. Mutation Research, 259, 363–385. https://doi.org/10.1016/0165-1218(91)90128-9.

    Article  CAS  PubMed  Google Scholar 

  32. Deza-Ponzio, R., Herrera, M. L., Bellini, M. L., Virgolini, M. B., & Hereñú, C. B. (2018). Aldehyde dehydrogenase 2 in the spotlight: the link between mitochondria and neurodegeneration. Neurotoxicology, 68, 19–24. https://doi.org/10.1016/j.neuro.2018.06.005.

    Article  CAS  PubMed  Google Scholar 

  33. Chen, C. H., Ferreira, J. C. B., Gross, E. R., & Mochly-Rosen, D. (2014). Targeting aldehyde dehydrogenase 2: new therapeutic opportunities. Physiological Reviews, 94(1), 1–34. https://doi.org/10.1152/physrev.00017.2013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Vasiliou, V., & Nebert, D. W. (2005). Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family. Human Genomics, 2(2), 138–143. https://doi.org/10.1186/1479-7364-2-2-138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Quiñonero, F., Mesas, C., Doello, K., Cabeza, L., Perazzoli, G., Jimenez-Luna, C., Rama, A. R., Melguizo, C., & Prados, J. (2019). The challenge of drug resistance in pancreatic ductal adenocarcinoma: a current overview. Cancer Biology & Medicine, 16(4), 688–699. https://doi.org/10.20892/j.issn.2095-3941.2019.0252.

    Article  CAS  Google Scholar 

  36. Dorokhov, Y. L., Sheshukova, E. V., Bialik, T. E., & Komarova, T. V. (2018). Human endogenous formaldehyde as an anticancer metabolite: its oxidation downregulation may be a means of improving therapy. BioEssays, 40(1800), 136. https://doi.org/10.1002/bies.201800136.

    Article  CAS  Google Scholar 

  37. Sophos, N. A., & Vasiliou, V. (2003). Aldehyde dehydrogenase gene superfamily: the 2002 update. Chemico-Biological Interactions, 143–144, 5–22. https://doi.org/10.1016/s0009-2797(02)00163-1.

    Article  PubMed  Google Scholar 

  38. Gross, E. R., Zambelli, V. O., Small, B. A., Ferreira, J. C. B., Chen, C. H., & Mochly-Rosen, D. (2015). A personalized medicine approach for Asian Americans with the aldehyde dehydrogenase 2*2 variant. Annual Review of Pharmacology and Toxicology, 55, 107–127. https://doi.org/10.1146/annurev-pharmtox-010814-124915.

    Article  CAS  PubMed  Google Scholar 

  39. Petersen, D. R., & Doorn, J. A. (2004). Reactions of 4-hydroxynonenal with proteins and cellular targets. Free Radical Biology & Medicine, 37, 937–945. https://doi.org/10.1016/j.freeradbiomed.2004.06.012.

    Article  CAS  Google Scholar 

  40. Goldstein, D. S., Sullivan, P., Holmes, C., Miller, G. W., Alter, S., Strong, R., & Sharabi, Y. (2013). Determinants of buildup of the toxic dopamine metabolite DOPAL in Parkinson’s disease. Journal of Neurochemistry, 126(5), 591–603. https://doi.org/10.1111/jnc.12345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Ohsawa, I., Kamino, K., Nagasaka, K., Ando, F., Niino, N., Shimokata, H., & Ohta, S. (2003). Genetic deficiency of a mitochondrial aldehyde dehydrogenase increases serum lipid peroxides in community-dwelling females. Journal of Human Genetics, 48(8), 404–409. https://doi.org/10.1007/s10038-003-0046-y.

    Article  CAS  PubMed  Google Scholar 

  42. Bradley, M. A., Markesbery, W. R., & Lovell, M. A. (2010). Increased levels of 4-hydroxynonenal and acrolein in the brain in preclinical Alzheimer disease. Free Radical Biology & Medicine, 48(12), 1570–1576. https://doi.org/10.1016/j.freeradbiomed.2010.02.016.

    Article  CAS  Google Scholar 

  43. Shoeb, M., Ansari, N. H., Srivastava, S. K., & Ramana, K. V. (2014). 4-hydroxynonenal in the pathogenesis and progression of human diseases. Current Medicinal Chemistry, 21(2), 230–237. https://doi.org/10.2174/09298673113209990181.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Dinavahi, S. S., Bazewicz, C. G., Gowda, R., & Robertson, G. P. (2019). Aldehyde dehydrogenase inhibitors for cancer therapeutics. Trends in Pharmacological Sciences, 40(10), 774–789. https://doi.org/10.1016/j.tips.2019.08.002.

    Article  CAS  PubMed  Google Scholar 

  45. Boocock, D. J., Faust, G. E. S., Patel, K. R., Schinas, A. M., Brown, V. A., Ducharme, M. P., Booth, T. D., Crowel, J. A., Perloff, M., Gescher, A. J., Steward, W. P., & Brenner, D. E. (2007). Phase I dose escalation pharmacokinetic study in healthy volunteers of resveratrol, a potential cancer chemopreventive agent. Cancer Epidemiology, Biomarkers & Prevention, 16, 1246–1252. https://doi.org/10.1158/1055-9965.EPI-07-0022.

    Article  CAS  Google Scholar 

  46. Osmond, G. W., Masko, E. M., Tyler, D. S., Freedland, S. J., & Pizzo, S. (2013). In vitro and in vivo evaluation of resveratrol and 3,5-dihydroxy-4′-acetoxy-trans-stilbene in the treatment of human prostate carcinoma and melanoma. Journal of Surgical Research, 179(1), e141–e148. https://doi.org/10.1016/j.jss.2012.02.057.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the doctoral fund project of Jilin University of Chemical Technology, People’s Republic of China (No. 2012121).

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Yanbin Su and Chengyu Sun contributed to the study conception and design. Material preparation and data collection were performed by Xuwei Sun, Ruixue Wu, Xing Zhang, and Yunzhou Tu. Data analysis were performed by Yanbin Su. The first draft of the manuscript was written by Yanbin Su. All authors commented on versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yanbin Su.

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Highlights

1. The toxic −CH=O Raman band of TCA was dragged by the Acetyl-Res.

2. The above process was regulated by pH which weakly acid was the best.

3. The Acetyl-Res as a potential substitute for the Res applied to anticancer

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Su, Y., Sun, C., Sun, X. et al. Acetylresveratrol as a Potential Substitute for Resveratrol Dragged the Toxic Aldehyde to Inhibit the Mutation of Mitochondrial DNA. Appl Biochem Biotechnol 191, 1340–1352 (2020). https://doi.org/10.1007/s12010-020-03279-w

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