Investigation of the effects of Eremurus spectabilis Bieb. lyophilized and nanoparticle extracts on the cellular and enzymatic immune system in experimentally-induced hepatocellular carcinogenesis in rats

Year 2024, Volume: 5 Issue: 2, 95 - 100, 30.08.2024

Dilara Genç , İsmail Çelik

https://doi.org/10.51753/flsrt.1395612

Abstract

Cancer is the leading cause of death after cardiovascular diseases. Hepatocellular carcinoma (HCC) constitutes the majority of primary malignancies of the liver. In this study, the effects of Eremurus spectabilis lyophilize and nanoparticle plant leaves extracts (LPLE-NPLE) were carried out on cellular and enzymatic immune system of hepatocellular carcinoma experimentally induced with diethylnitrosamine (DEN) in rats. The aims of study, it is to investigate the plant leaf extracts on T lymphocyte subsets mature T lymphocyte (CD3+), helper T lymphocyte (CD4+), suppressor-cytotoxic T lymphocyte (CD8+) and the CD4+/CD8+ as cellular immune systems. Further, it is aim to determinate activity of myeloperoxidase (MPO) and adenosine deaminase (ADA) activities in lung and spleen tissues of rats as enzymatic immune systems too. The study was conducted on six groups in each group 6 rats as normal control (NC), cancer control (CC), cancer+50 mg LPLE/kg (CLPLE1), cancer+100 mg LPLE/kg (CLPLE2), cancer+50 mg NPLE/kg (CNPLE1) and cancer+100 mg NPLE/kg (CNPLE2). To reveal the effects of the plant extracts in rats treated with two doses on cellular and enzymatic constituents of immune systems, the blood, spleen and lung samples were taken from rats at the end experiment. CD3+, CD4+, CD8+ cells and CD4+/CD8+ ratio was analysed by flow cytometry in blood samples. Furthermore, MPO and ADA enzyme activities were analyzed in supernatants of the lung and spleen tissues. According to the obtained results; CD3+ and CD8+ T cells of CLPLE1 bases were statistically reduced compare with NC and CC groups. Again, a significant decrease was found statistically the CNPLE2 group compared to the NC and CC groups. CD4+ T cells were significantly decreased compared to NC. On the other hand, ADA enzyme, which is an enzyme of the immune system, decreased in CC compared to NC, while it increased in lung and spleen tissues in CNPLE1, CNPLE2, CLPLE1 and CLPLE2 groups. Regarding the MPO; In the groups supplemented with plant extract, MPO enzyme activity increased in both lung and spleen tissues compared to NC and CC. According to these results, the manuscript results present some new data and original theory about healing effects of E. spectabilis LPLE and NPLE on experimentally induced cancer complications as constituent of immune system with DEN. But it was concluded that more studies are needed to reveal the mechanism of action of E. spectabilis in cancer treatment and its therapeutic use.

Keywords

Cellular and enzymatic immune system, Eremurus spectabilis, hepatocellular carcinoma

References

• Antonioli, L., Colucci, R., La Motta, C., Tuccori, M., Awwad, O., Da Settimo, F., ... & Fornai, M. (2012). Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders. Current Drug Targets, 13(6), 842-862.
• Baytop, T. (1984). Treatment with plants in Turkey. Istanbul University Press, 3255, 1-376.
• Bradley, P. P., Priebat, D. A., Christensen, R. D., & Rothstein, G. (1982). Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker, Journal of Investigative Dermatology, 78, 206-209.
• Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394-424.
• Celik, I., Temur, A., & Isik, I. (2009). Hepatoprotective role and antioxidant capacity of pomegranate (Punica granatum) flowers infusion against trichloroacetic acid-exposed in rats. Food and Chemical Toxicology, 47, 145-149.
• Choudhari, A. S., Mandave, P. C., Deshpande, M., Ranjekar, P., & Prakash, O. (2020). Phytochemicals in cancer treatment: From preclinical studies to clinical practice. Frontiers in Pharmacology, 10, 1614.
• Dalar, A., & Konczak, I. (2013). Phenolic contents, antioxidant capacities and inhibitory activities against key metabolic syndrome relevant enzymes of herbal teas from Eastern Anatolia. Industrial Crops and Products. 44, 383-390.
• Durak, I., Isik, C. U., Canbolat, O., Akyol, O., & Kavutcu, M. (1993). Adenosine deaminase, 5′ nucleotidase, xanthine oxidase, superoxide dismutase, and catalase activities in cancerous and noncancerous human laryngeal tissues. Free Radical Biology and Medicine, 15(6), 681-684.
• El-Serag, H. B., & Rudolph, K. L. (2007). Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology, 132(7), 2557-2576.
• Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., ... & Bray, F. (2015). Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. International journal of cancer, 136(5), E359-E386.
• Bergmeyer, H. U. (1974). Methods of enzymatic analysis. Volume 3 (No. Ed. 2, pp. 1125-1624). Academic Press, New York.
• Gulcin, I. (2020). Antioxidants and antioxidant methods: An updated overview. Archives of Toxicology, 94(3), 651-715.
• Gungor, F. (2002). Research on the morphological and biological characteristics and cultivability possibilities of wild yew (Eremurus spectabilis (Bieb.) Fedtsch.), yew (Prangos ferulacea Lindl.) and yellow lily (Hippomarathrum microcarpum Bieb.) plants. Doctoral Thesis, Ataturk University, Institute of Sciences, Erzurum, Turkiye.
• Hassan, H. A., Ghareb, N. E., & Azhari, G. F. (2017). Antioxidant activity and free radical-scavenging of cape gooseberry (Physalis peruviana L.) in hepatocellular carcinoma rats model. Hepatoma Research, 3, 27-33.
• Heindryckx, F., Colle, I., & Van Vlierberghe, H. (2009). Experimental mouse models for hepatocellular carcinoma research. International Journal of Experimental Pathology, 90(4), 367-386.
• Islam, M. T., Ali, E. S., & Mubarak, M. S. (2020). Anti‐obesity effect of plant diterpenes and their derivatives: a review. Phytotherapy Research, 34(6), 1216-1225.
• Karakurt, E. (2018). Investigation of the protective effect of silymarin in an experimental liver cancer model in rats using histopathological and biochemical methods. Doctoral Thesis, Institute of Health Sciences, Kars, Türkiye.
• Karaoğlan, E. S., Albayrak, A., Kutlu, Z., & Bayır, Y. (2018). Gastroprotective and antioxidant effects of Eremurus spectabilis Bieb. methanol extract and its isolated component isoorientin on indomethacin induced gastric ulcers in rats. Acta Cirurgica Brasileira, 33, 609-618.
• Koizumi, H., Tomizawa, K., Tanaka, H., Kumakiri, M., & Ohkawara, A. (1993). Clinical significance of serum adenosine deaminase activity in patients with mycosis fungoides. The Journal of Dermatology, 20(7), 394-399.
• Moreira, A. J., Ordoñez, R., Cerski, C. T., Picada, J. N., García-Palomo, A., Marroni, N. P., ... & González-Gallego, J. (2015). Melatonin activates endoplasmic reticulum stress and apoptosis in rats with diethylnitrosamine-induced hepatocarcinogenesis. PLoS One, 10(12), e0144517.
• Hiromu, N., Hitoshi, A., Hiroko, O., & Shoji, H. (1970). Multienzyme patterns of serum adenosine deaminase by agar gel electrophoresis: an evaluation of the diagnostic value in lung cancer. Clinica Chimica Acta, 30(2), 251-258.
• Nussbaum, C., Klinke, A., Adam, M., Baldus, S., & Sperandio M. (2013). Myeloperoxidase: a leukocyte-derived protagonist of inflammation and cardiovascular disease. Antioxidants and redox signaling, 18, 692-713.
• Ozkol, H., Musa, D., Tuluce, Y., & Koyuncu I. (2012). Ameliorative influence of Urtica dioica L against cisplatin-induced toxicity in mice bearing Ehrlich ascites carcinoma. Drug and Chemical Toxicology, 35, 251-257.
• Ozok, N., & Celik I., (2019). Investigation of the effects of linden (Tilia platyphyllos Scop) infusion on immune system in rats. BEU Journal of Science, 8(3), 852-858.
• Romualdo, G. R., Grassi, T. F., Goto, R. L., Tablas, M. B., Bidinotto, L. T., Fernandes, A. A. H., ... & Barbisan, L. F. (2017). An integrative analysis of chemically-induced cirrhosis-associated hepatocarcinogenesis: Histological, biochemical and molecular features. Toxicology Letters, 281, 84-94.
• Sahiner, N., & Sengel, S. B. (2016). Tannic acid decorated poly (methacrylic acid) micro and nanoparticles with controllable tannic acid release and antioxidant properties. Colloids and Surfaces A: Physicochemical and Engineering Aspects, 508, 30-38.
• Salehi, B., Stojanović-Radić, Z., Matejić, J., Sharifi-Rad, M., Kumar, N. V. A., Martins, N., & Sharifi-Rad, J. (2019). The therapeutic potential of curcumin: A review of clinical trials. European Journal of Medicinal chemistry, 163, 527-545.
• Schiappacasse, F., Szigeti, J. C., Manzano, E., & Kamenetsky, R. (2012). Eremurus as a new cut flower crop in Aysen, Chile: introduction from the northern hemisphere. XI International Symposium on Flower Bulbs and Herbaceous Perennials 1002, 115-121.
• Sideras, K., Galjart, B., Vasaturo, A., Pedroza‐Gonzalez, A., Biermann, K., Mancham, S., ... & Bruno, M. J. (2018). Prognostic value of intra‐tumoral CD8+/FoxP3+ lymphocyte ratio in patients with resected colorectal cancer liver metastasis. Journal of Surgical Oncology, 118(1), 68-76.
• Sufrin, G., Tritsch, G. L., Mittelman, A., & Murphy, G. P. (1978). Adenosine deaminase activity in patients with carcinoma of the bladder. The Journal of Urology, 119(3), 343-346.
• Sun, J. H., Luo, Q., Liu, L. L., & Song, G. B. (2016). Liver cancer stem cell markers: progression and therapeutic implications. World Journal of Gastroenterology, 22(13), 3547.
• Tolba, R., Kraus, T., Liedtke, C., Schwarz, M., & Weiskirchen, R. (2015). Diethylnitrosamine (DEN)-induced carcinogenic liver injury in mice. Laboratory Animals, 49(1_suppl), 59-69.
• Tuzlaci, E. (1987). Türkiye’ nin çiriş otları (II): Asphodeline, Asphodelus, Eremurus ve Anthericum cinsleri üzerinde morfolojik karşılaştırmalar. Marmara Pharmaceutical Journal, 3, 19-26.
• Tuzlaci, E., & Dogan, A. (2010). Turkish folk medicinal plants, IX: Ovacık (Tunceli). Marmara Pharmaceutical Journal, 14, 136-143.
• Tuzlacı, E. (1985). Türkiye'de bitkilerin yöresel kullanılışları. Marmara Pharmaceutical Journal, 1(1-2), 101-106.
• Uchida, N. S., Silva-Filho, S. E., Cardia, G. F. E., Cremer, E., Silva-Comar, F. M. D. S., Silva, E. L., ... & Cuman, R. K. N. (2017). Hepatoprotective effect of citral on acetaminophen‐induced liver toxicity in mice. Evidence‐Based Complementary and Alternative Medicine, 2017(1), 1796209.
• Vesselinovitch, S. D., & Mihailovich, N. (1983). Kinetics of diethylnitrosamine hepatocar-cinogenesis in the infant mouse. Cancer Research, 43, 4253-4259.
• Vesselinovitch, S. D., Koka, M., Mihailovich, N., & Rao, K. V. N. (1984). Carcinogenicity of diethylnitrosamine in newborn, infant, and adult mice. Journal of Cancer Research and Clinical Oncology, 108(1), 60-65.
• Vizzotto, G. (2018). Effect of flower pollination on fruit set and cropping in apple. American Journal of Agriculture and Forestry, 6, 156.
• Yarchoan, M., Xing, D., Luan, L., Xu, H., Sharma, R. B., Popovic, A., ... & Anders, R. A. (2017). Characterization of the immune microenvironment in hepatocellular carcinoma. Clinical Cancer Research, 23(23), 7333-7339.
• Zhao, Y., Ge, X., He, J., Cheng, Y., Wang, Z., Wang, J., & Sun, L. (2019). The prognostic value of tumor-infiltrating lymphocytes in colorectal cancer differs by anatomical subsite: a systematic review and meta-analysis. World Journal of Surgical Oncology, 17, 1-11.