DOSE-DEPENDENT CHANGES IN BIOMARKERS OF OXIDATIVE STRESS IN HUMAN ERYTHROCYTES FOLLOWING IN VITRO TREATMENT WITH EXTRACTS FROM BERRIES OF EUROPEAN MISTLETOE (VISCUM ALBUM L.)

Authors

DOI:

https://doi.org/10.32782/naturaljournal.7.2024.1

Keywords:

European mistletoe (Viscum album L.), human blood, extracts, 2-thiobarbituric acid reactive substances (TBARS), carbonyl derivatives of oxidative modification of proteins, total antioxidant capacity (TAC)

Abstract

Radical scavenging activity and protective effects against oxidative stress caused by free radicals, nitric oxide and superoxide anion have been demonstrated for a number of mistletoe extracts and isolated lectins. The aim of the present study was to determine the antioxidant activity of extracts from the berries of mistletoe (Viscum album L.). For this purpose, biomarkers of oxidative stress [2-thiobarbituric acid reactive substances (TBARS) as a biomarker of lipid peroxidation, carbonyl derivatives of oxidative modification of proteins, total antioxidant capacity (TAC)] were used in human blood after in vitro incubation with extracts derived from mistletoe berries at two final concentrations (5 and 2.5 mg/mL). The results of our study showed that treatment with mistletoe berry extracts resulted in a significant increase in TBARS levels in human erythrocytes after in vitro treatment with extracts at final concentrations of 5 mg/mL compared to untreated samples. On the other hand, a statistically non-significant decrease in TBARS levels was observed for the extract at a final concentration of 2.5 mg/ mL. The levels of aldehydic derivatives of oxidatively modified proteins were statistically significantly increased in samples treated in vitro with mistletoe berry extracts at a final concentration of 5 mg/mL compared to untreated samples, and this increase was statistically significant. Treatment of human erythrocytes with mistletoe berry extracts at a final concentration of 2.5 mg/mL resulted in a statistically significant decrease in the levels of aldehydic derivatives of oxidatively modified proteins. The reduction was 24.1% (p < 0.05). When human erythrocytes were incubated with mistletoe berry extracts, the levels of ketonic derivatives of OMP were at the same level as in untreated samples. Treatment of human erythrocytes with mistletoe berry extracts at a final concentration of 2.5 mg/ml resulted in a statistically non-significant decrease in the levels of ketonic derivatives of oxidatively modified proteins. TAC levels in human erythrocytes were increased after in vitro incubation with mistletoe berry extracts (final concentration of 5 mg/mL) compared to untreated samples. This represented a 29% (p < 0.05) increase in TAC levels compared to untreated samples. TAC levels in human erythrocytes after in vitro incubation with mistletoe berry extracts (final concentration 2.5 mg/mL) were at the same level as in untreated samples. Future studies can add to the current findings to better understand the antioxidant properties of mistletoe berry extracts, with the potential to develop treatments and products using these extracts.

References

Amarowicz, R., & Pegg, R.B. (2019). Natural antioxidants of plant origin. Advances in food and nutrition research, 90, 1–81. https://doi.org/10.1016/bs.afnr.2019.02.011 [in English].

Bartosz, G. (2003). Total antioxidant capacity. Advances in clinical chemistry, 37, 219–292. https://doi.org/10.1016/s0065-2423(03)37010-6 [in English].

Benzie, I.F. (2000). Evolution of antioxidant defence mechanisms. European journal of nutrition, 39 (2), 53–61. https://doi.org/10.1007/s003940070030 [in English].

Berlett, B.S., & Stadtman, E.R. (1997). Protein oxidation in aging, disease, and oxidative stress. The Journal of biological chemistry, 272 (33), 20313–20316. https://doi.org/10.1074/jbc.272.33.20313 [in English].

Beztsinna, N., de Matos, M.B.C., Walther, J., Heyder, C., Hildebrandt, E., Leneweit, G., Mastrobattista, E., & Kok, R.J. (2018). Quantitative analysis of receptor-mediated uptake and pro-apoptotic activity of mistletoe lectin-1 by high content imaging. Scientific reports, 8 (1), 2768. https://doi.org/10.1038/s41598-018-20915-y [in English].

Buege, J.A., & Aust, S.D. (1978). Microsomal lipid peroxidation. Methods Enzymol, 52, 302-310. https://doi.org/10.1016/s0076-6879(78)52032-6 [in English].

Carlsen, M.H., Halvorsen, B.L., Holte, K., Bøhn, S.K., Dragland, S., Sampson, L., Willey, C., Senoo, H., Umezono, Y., Sanada, C., Barikmo, I., Berhe, N., Willett, W. C., Phillips, K. M., Jacobs, D.R., Jr, & Blomhoff, R. (2010). The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutrition journal, 9, 3. https://doi.org/10.1186/1475-2891-9-3 [in English].

Çetin, E.S., Sozen, H., Celik, O.I., Cigerci, I.H., & Yılmaz, N. (2023). Mistletoe (Viscum album L.) extract attenuates ıtraconazole-ınduced acute oxidative stress and hepatocellular ınjury in rats. Pakistan journal of pharmaceutical sciences, 36 (1), 9–16 [in English].

Dalle-Donne, I., Rossi, R., Giustarini, D., Milzani, A., & Colombo, R. (2003). Protein carbonyl groups as biomarkers of oxidative stress. Clinica chimica acta; international journal of clinical chemistry, 329 (1-2), 23–38. https://doi.org/10.1016/s0009-8981(03)00003-2 [in English].

Demirci-Çekiç, S., Özkan, G., Avan, A.N., Uzunboy, S., Çapanoğlu, E., & Apak, R. (2022). Biomarkers of Oxidative Stress and Antioxidant Defense. Journal of pharmaceutical and biomedical analysis, 209, 114477. https://doi.org/10.1016/j.jpba.2021.114477 [in English].

Hajam, Y.A., Rani, R., Ganie, S.Y., Sheikh, T.A., Javaid, D., Qadri, S.S., Pramodh, S., Alsulimani, A., Alkhanani, M.F., Harakeh, S., Hussain, A., Haque, S., & Reshi, M.S. (2022). Oxidative Stress in Human Pathology and Aging: Molecular Mechanisms and Perspectives. Cells, 11 (3), 552. https://doi.org/10.3390/cells11030552 [in English].

Halvorsen, B.L., Holte, K., Myhrstad, M.C., Barikmo, I., Hvattum, E., Remberg, S.F., Wold, A.B., Haffner, K., Baugerød, H., Andersen, L.F., Moskaug, Ø., Jacobs, D.R., Jr, & Blomhoff, R. (2002). A systematic screening of total antioxidants in dietary plants. The Journal of nutrition, 132 (3), 461–471. https://doi.org/10.1093/jn/132.3.461 [in English].

Khalili, J., & Biloklytska, H.F. (2008). Salivary malondialdehyde levels in clinically healthy and periodontal diseased individuals. Oral diseases, 14 (8), 754–760. https://doi.org/10.1111/j.1601-0825.2008.01464.x [in English].

Khwaja, T.A., Wajahat, T., Ahmad, I., Hoessli, D.C., Walker-Nasir, E., Kaleem, A., Qazi, W.M., Shakoori, A.R., & Din, N.U. (2008). In silico modulation of apoptotic Bcl-2 proteins by mistletoe lectin-1: functional consequences of protein modifications. Journal of cellular biochemistry, 103 (2), 479–491. https://doi.org/10.1002/jcb.21412 [in English].

Kienle, G.S., & Kiene, H. (2010). Review article: Influence of Viscum album L (European mistletoe) extracts on quality of life in cancer patients: a systematic review of controlled clinical studies. Integrative cancer therapies, 9 (2), 142–157. https://doi.org/10.1177/1534735410369673 [in English].

Kienle, G.S., Grugel, R., & Kiene, H. (2011). Safety of higher dosages of Viscum album L. in animals and humans – systematic review of immune changes and safety parameters. BMC complementary and alternative medicine, 11, 72. https://doi.org/10.1186/1472-6882-11-72 [in English].

Kim, B.K., Choi, M.J., Park, K.Y., & Cho, E.J. (2010). Protective effects of Korean mistletoe lectin on radical-induced oxidative stress. Biological & pharmaceutical bulletin, 33 (7), 1152–1158. https://doi.org/10.1248/bpb.33.1152 [in English].

Kim, M.J., Park, J.H., Kwon, D.Y., Yang, H.J., Kim, D.S., Kang, S., Shin, B.K., Moon, N.R., Song, B.S., Kim, J.H., & Park, S. (2015). The supplementation of Korean mistletoe water extracts reduces hot flushes, dyslipidemia, hepatic steatosis, and muscle loss in ovariectomized rats. Experimental biology and medicine (Maywood, N.J.), 240 (4), 477–487. https://doi.org/10.1177/1535370214551693 [in English].

Kim, S.Y., Yang, E.J., Son, Y.K., Yeo, J.H., & Song, K.S. (2016). Enhanced anti-oxidative effect of fermented Korean mistletoe is originated from an increase in the contents of caffeic acid and lyoniresinol. Food & function, 7 (5), 2270–2277. https://doi.org/10.1039/c6fo00138f [in English].

Kleszken, E., Purcarea, C., Pallag, A., Ranga, F., Memete, A.R., Miere Groza, F., & Vicas, S.I. (2022). Phytochemical Profile and Antioxidant Capacity of Viscum album L. subsp. album and Effects on Its Host Trees. Plants (Basel, Switzerland), 11 (22), 3021. https://doi.org/10.3390/plants11223021 [in English].

Kozłowska, A., & Szostak-Wegierek, D. (2014). Flavonoids – food sources and health benefits. Roczniki Panstwowego Zakladu Higieny, 65 (2), 79–85 [in English].

Kurhaluk, N., Tkachenko, H., & Tomin, V. (2023). In vitro impact of a combination of red and infrared LEDs, infrared laser and magnetic field on biomarkers of oxidative stress and hemolysis of erythrocytes sampled from healthy individuals and diabetes patients. Journal of photochemistry and photobiology. B, Biology, 242, 112685. https://doi.org/10.1016/j.jphotobiol.2023.112685 [in English].

Levine, R.L., Garland, D., Oliver, C.N., Amici, A., Climent, I., Lenz, A.G., Ahn, B.W., Shaltiel, S., & Stadtman, E.R. (1990). Determination of carbonyl content in oxidatively modified proteins. Methods in enzymology, 186, 464–478. https://doi.org/10.1016/0076-6879(90)86141-h [in English].

Liu, R.H. (2013). Dietary bioactive compounds and their health implications. Journal of food science, 78 Suppl 1, A18–A25. https://doi.org/10.1111/1750-3841.12101 [in English].

Liu, X., Hussain, R., Mehmood, K., Tang, Z., Zhang, H., & Li, Y. (2022). Mitochondrial-Endoplasmic Reticulum Communication-Mediated Oxidative Stress and Autophagy. BioMed research international https://doi.org/10.1155/2022/6459585 [in English].

Lourenço, S.C., Moldão-Martins, M., & Alves, V.D. (2019). Antioxidants of Natural Plant Origins: From Sources to Food Industry Applications. Molecules (Basel, Switzerland), 24 (22), 4132. https://doi.org/10.3390/molecules24224132 [in English].

Luo, J., Mills, K., le Cessie, S., Noordam, R., & van Heemst, D. (2020). Ageing, age-related diseases and oxidative stress: What to do next? Ageing research reviews, 57, 100982. https://doi.org/10.1016/j.arr.2019.100982 [in English].

Majeed, M., Pirzadah, T.B., Mir, M.A., Hakeem, K.R., Alharby, H.F., Alsamadany, H., Bamagoos, A.A., & Rehman, R.U. (2021). Comparative Study on Phytochemical Profile and Antioxidant Activity of an Epiphyte, Viscum album L. (White Berry Mistletoe), Derived from Different Host Trees. Plants (Basel, Switzerland), 10 (6), 1191. https://doi.org/10.3390/plants10061191 [in English].

Melzer, J., Iten, F., Hostanska, K., & Saller, R. (2009). Efficacy and safety of mistletoe preparations (Viscum album) for patients with cancer diseases. A systematic review. Forschende Komplementarmedizin (2006), 16 (4), 217–226. https://doi.org/10.1159/000226249 [in English].

Mistletoe. (1987). Nursing standard (Royal College of Nursing (Great Britain), 2(13), 28. https://doi.org/10.7748/ns.2.13.28.s62 [in English].

Nazaruk, J., & Orlikowski, P. (2016). Phytochemical profile and therapeutic potential of Viscum album L. Natural product research, 30 (4), 373–385. https://doi.org/10.1080/14786419.2015.1022776 [in English].

Nicoletti, M. (2023). The Anti-Inflammatory Activity of Viscum album. Plants (Basel, Switzerland), 12 (7), 1460. https://doi.org/10.3390/plants12071460 [in English].

Orhan, D.D., Aslan, M., Sendogdu, N., Ergun, F., & Yesilada, E. (2005). Evaluation of the hypoglycemic effect and antioxidant activity of three Viscum album subspecies (European mistletoe) in streptozotocin-diabetic rats. Journal of ethnopharmacology, 98 (1-2), 95–102. https://doi.org/10.1016/j.jep.2004.12.033 [in English].

Patil, S., Anarthe, S., Jadhav, R., & Surana, S. (2011). Evaluation of Anti-Inflammatory Activity and In - vitro Antioxidant Activity of Indian Mistletoe, the Hemiparasite Dendrophthoe falcate L. F. (Loranthaceae). Iranian journal of pharmaceutical research: IJPR, 10 (2), 253–259 [in English].

Radenkovic, M., Ivetic, V., Popovic, M., Brankovic, S., & Gvozdenovic, L. (2009). Effects of mistletoe (Viscum album L., Loranthaceae) extracts on arterial blood pressure in rats treated with atropine sulfate and hexocycline. Clinical and experimental hypertension (New York, N.Y.: 1993), 31 (1), 11–19. https://doi.org/10.1080/10641960802409820 [in English].

Rostock, M. (2020). Die Misteltherapie in der Behandlung von Patienten mit einer Krebserkrankung [Mistletoe in the treatment of cancer patients]. Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz, 63 (5), 535–540. https://doi.org/10.1007/s00103-020-03122-x [in English].

Squier, T.C. (2001). Oxidative stress and protein aggregation during biological aging. Experimental gerontology, 36 (9), 1539–1550. https://doi.org/10.1016/s0531-5565(01)00139-5 [in English].

Stefanucci, A., Zengin, G., Llorent-Martinez, E.J., Dimmito, M.P., Della Valle, A., Pieretti, S., Ak, G., Sinan, K.I., & Mollica, A. (2020). Viscum album L. homogenizer-assisted and ultrasound-assisted extracts as potential sources of bioactive compounds. Journal of food biochemistry, 44 (9), e13377. https://doi.org/10.1111/jfbc.13377 [in English].

Sunjic, S.B., Gasparovic, A.C., Vukovic, T., Weiss, T., Weiss, E.S., Soldo, I., Djakovic, N., Zarkovic, T., & Zarkovic, N. (2015). Adjuvant Cancer Biotherapy by Viscum Album Extract Isorel: Overview of Evidence Based Medicine Findings. Collegium antropologicum, 39 (3), 701–708 [in English].

Tapsell, L.C., Hemphill, I., Cobiac, L., Patch, C.S., Sullivan, D.R., Fenech, M., Roodenrys, S., Keogh, J.B., Clifton, P.M., Williams, P.G., Fazio, V.A., & Inge, K.E. (2006). Health benefits of herbs and spices: the past, the present, the future. The Medical journal of Australia, 185 (S4), S1–S24. https://doi.org/10.5694/j.1326-5377.2006.tb00548.x [in English].

Teleanu, D.M., Niculescu, A.G., Lungu, I.I., Radu, C.I., Vladâcenco, O., Roza, E., Costăchescu, B., Grumezescu, A.M., & Teleanu, R.I. (2022). An Overview of Oxidative Stress, Neuroinflammation, and Neurodegenerative Diseases. International journal of molecular sciences, 23 (11), 5938. https://doi.org/10.3390/ijms23115938 [in English].

Thronicke, A., Schad, F., Debus, M., Grabowski, J., & Soldner, G. (2022). Viscum album L. Therapy in Oncology: An Update on Current Evidence. Viscum album L. Therapie in der Onkologie: Ein Update zur bestehenden Evidenz. Complementary medicine research, 29 (4), 362–368. https://doi.org/10.1159/000524184 [in English].

Tiberi, J., Cesarini, V., Stefanelli, R., Canterini, S., Fiorenza, M.T., & La Rosa, P. (2023). Sex differences in antioxidant defence and the regulation of redox homeostasis in physiology and pathology. Mechanisms of ageing and development, 211, 111802. https://doi.org/10.1016/j.mad.2023.111802 [in English].

Turkkan, A., Savas, H.B., Yavuz, B., Yigit, A., Uz, E., Bayram, N.A., & Kale, B. (2016). The prophylactic effect of Viscum album in streptozotocin-induced diabetic rats. Northern clinics of Istanbul, 3 (2), 83–89. https://doi.org/10.14744/nci.2016.22932 [in English].

Valko, M., Leibfritz, D., Moncol, J., Cronin, M.T., Mazur, M., & Telser, J. (2007). Free radicals and antioxidants in normal physiological functions and human disease. The international journal of biochemistry & cell biology, 39 (1), 44–84. https://doi.org/10.1016/j.biocel.2006.07.001 [in English].

Zar, J.H. (1999). Biostatistical Analysis. 4th ed., Prentice-Hall Inc., Englewood Cliffs, New Jersey [in English].

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2024-04-08