Potential Protective Effects of Rice Seedling Extracts of a Malaysian Rice Variety, Biris, Against Doxorubicin-Induced Cytotoxicity
Main Article Content
Abstract
Doxorubicin (DOX) is one of the most effective chemotherapeutic drugs for treating a wide range of neoplasms such as leukaemia, lymphoma and breast cancer; however, it is often related to cardiomyopathy. Currently, there is no established treatment for reducing the impact of cardiomyopathy without noticeable side effects. Thus, this study set out to investigate potential protective effects of rice seedlings extracts (RSE) against DOX-induced cytotoxicity using in vitro cell culture studies. The antioxidant capabilities of RSE were evaluated, and the results showed lower amounts of total phenolic content (TPC), but similar total flavonoid content (TFC) and trolox equivalent antioxidant capacity (TEAC), compared to wheatgrass seedlings extracts. A series of absorbance and fluorescence spectroscopy experiments indicated that RSE could hinder the formation of DOX-DNA complexes at the tested concentrations. Further, the viability of a rat cardiomyocyte cell line, H9c2(2-1), was tested after 24, 48 and 72 h of DOX treatments in the presence of RSE, using a tetrazolium salt (MTS reagent) based cell proliferation assay. The results indicated significant protective effects of RSE against DOX-induced cytotoxicity. The nasopharyngeal carcinoma cell line, HK1, was used as a control to determine whether the efficacy of DOX is affected by the co-administration of RSE. The results indicated no negative effects on the efficacy of the drug. These multiple beneficial properties of RSE indicate its strong potential for development of a cardioprotective agent to compliment the DOX treatment in clinical settings.
Doxorubicin (DOX) adalah salah satu ubat kemoterapi yang paling berkesan untuk merawat pelbagai neoplasma seperti leukemia, limfoma dan kanser payudara. Walau bagaimanapun, ia sering dikaitkan dengan kardiomiopati. Pada masa ini, tiada rawatan yang sesuai untuk mengurangkan kesan kardiomiopati tanpa kesan sampingan yang ketara. Oleh itu, kajian ini bertujuan untuk mengkaji kesan-kesan perlindungan potensi ekstrak benih padi (RSE) terhadap kesitotoksikan yang disebabkan oleh DOX menggunakan kajian kultur sel vitro. Keupayaan antioksidan RSE dinilai, dan hasilnya menunjukkan jumlah kandungan fenolik yang lebih rendah (TPC), tetapi jumlah kandungan flavonoid total (TFC) dan kapasiti antioksidan yang setara trolox (TEAC), dibandingkan dengan ekstrak benih wheatgrass. Satu siri eksperimen spektroskopi penyerapan dan pendarfluor menunjukkan bahawa RSE boleh menghalang pembentukan kompleks DOX-DNA pada kepekatan yang diuji. Tambahan pula, daya maju sel kardiomiosit sel, H9c2 (2-1), telah diuji selepas 24, 48 dan 72 jam rawatan DOX terhadap RSE menggunakan ujian proliferasi sel berdasarkan garam tetrazolium (MTS reagent). Hasilnya menunjukkan kesan perlindungan yang signifikan terhadap RSE terhadap kesitotoksikan yang disebabkan oleh DOX. Jalur sel karsinoma nasofarinks, HK1, digunakan sebagai kawalan untuk menentukan sama ada keberkesanan DOX terjejas oleh pentadbiran bersama RSE. Hasilnya tidak menunjukkan kesan negatif terhadap keberkesanan dadah. Pelbagai sifat berfaedah RSE menunjukkan potensi kuatnya untuk membangunkan agen kardioprotektif untuk melengkapi rawatan DOX dalam tetapan klinikal.
Article Details
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
Agudelo D, Bourassa P, Beauregard M, Bérubé G and Tajmir-Riahi H. (2013). tRNA binding to antitumor drug doxorubicin and its analogue. PLoS One 8(7): e69248. https://doi.org/10.1371/journal.pone.0069248
Ben-Arye E, Goldin E, Wengrower D, Stamper A, Kohn R & Berry E. (2002). Wheat grass juice in the treatment of active distal ulcerative colitis: A randomized double-blind placebo-controlled trial. Scandinavian Journal Gastroenterology 37(4): 444–449. https://doi.org/10.1080/003655202317316088
Carvalho C, Santos R, Cardoso S, Correia S, Oliveira P, Santos M and Moreira P. (2009). Doxorubicin: The good, the bad and the ugly effect. Current Medicinal Chemistry 16(25): 3267–3285. https://doi.org/10.2174/092986709788803312
Chegaev K, Riganti C, Rolando B, Lazzarato L, Gazzano E, Guglielmo S, Ghigo D, Fruttero R and Gasco A. (2013) Doxorubicin-antioxidant co-drugs. Bioorganic & Medicinal Chemistry Letters 23(19): 5307–5310. https://doi.org/10.1016/j.bmcl.2013.07.070
Chomchan R, Siripongvutikorn S, Puttarak P and Rattanapon R. (2016). Investigation of phytochemical constituents, phenolic profiles and antioxidant activities of ricegrass juice compared to wheatgrass juice. Functional Foods in Health and Disease 6(12): 822–835. https://doi.org/10.31989/ffhd.v6i12.290
EC (1994) Commission Directive 94/36/EC. Official Journal of the European Communities L237: 13–29.
Egner P, Muñoz A and Kensler T. (2003). Chemoprevention with chlorophyllin in individuals exposed to dietary aflatoxin. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 523: 209–216. https://doi.org/10.1016/S0027-5107(02)00337-8
Garc?a-Rodr?guez M, López-Santiago V and Altamirano-Lozano M. (2001). Effect of chlorophyllin on chromium trioxide-induced micronuclei in polychromatic erythrocytes in mouse peripheral blood. Mutation Research-Genetic Toxicology and Environmental Mutagenesis 496(1–2): 145–151. https://doi.org/10.1016/S1383-5718(01)00225-X
Hayatsu H, Sugiyama C, Arimoto KS and Negishi T. (1999). Porphyrins as possible preventers of heterocyclic amine carcinogenesis. Cancer Letters 143(2): 185–187. https://doi.org/10.1016/S0304-3835(99)00122-6
Hemalatha R, Karthik M, Babu K and Kumar B. (2012). Immunomodulatory activity of Triticum aestivum and its effects on Th1/Th2 cytokines and NF?B P 65 response. American Journal of Biochemistry and Biotechnology 2(1): 19–25.
Herald T, Gadgil P and Tilley M. (2012) High-throughput micro plate assays for screening flavonoid content and DPPH-scavenging activity in sorghum bran and flour. Journal of the Science of Food and Agriculture 92(11): 2326–2331. https://doi.org/10.1002/jsfa.5633
Hescheler J, Meyer R, Plant S, Krautwurst D, Rosenthal W and Schultz G. (1991). Morphological, biochemical, and electrophysiological characterization of a clonal cell (H9c2) line from rat heart. Circulation Research 69(6): 1476–1486. https://doi.org/10.1161/01.RES.69.6.1476
Hernaez J, Xu M and Dashwood R. (1997). Effects of tea and chlorophyllin on the mutagenicity of N-hydroxy-IQ: Studies of enzyme inhibition, molecular complex formation, and degradation/scavenging of the active metabolites. Environmental and Molecular Mutagenesis 30(4): 468. https://doi.org/10.1002/(SICI)1098-2280(1997)30:4%3C468::AID-EM12%3E3.0.CO;2-B
Hochster H. (1998). Clinical pharmacology of dexrazoxane. Seminars in Oncology 4 (Suppl.10): 37–42.
Huang D P, Ho J H C, Poon Y F, Chew E C, Saw D, Lui M, Li C L, Mak L S, Lai S H and Lau W H. (1980). Establishment of a cell line (NPC/HK1) from a differentiated squamous carcinoma of the nasopharynx. International Journal of Cancer 26(2): 127–132. https://doi.org/10.1002/ijc.2910260202
Jia Z, Tang M and Wu J. (1999). The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chemistry 64(4): 555–559. https://doi.org/10.1016/S0308-8146(98)00102-2
Kalam K and Marwick T. (2013). Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: A systematic review and meta-analysis. European Journal of Cancer 49(13): 2900–2909. https://doi.org/10.1016/j.ejca.2013.04.030
Khanthapoka P, Muangpromb A and Sukronga S. (2015). Antioxidant activity and DNA protective properties of rice grass juices. Science Asia 41(2): 119–129. https://doi.org/10.2306/scienceasia1513-1874.2015.41.119
Kulkarni S, Tilak J, Acharya R, Rajurkar N, Devasagayam T and Reddy A. (2006). Evaluation of the antioxidant activity of wheatgrass (Triticum aestivum L) as a function of growth under different conditions. Phytotheraphy Research 20(3): 218–227. https://doi.org/10.1002/ptr.1838
Kumar S, Chaubey R, Devasagayam T, Priyadarsini K and Chauhan P. (1999). Inhibition of radiation-induced DNA damage in plasmid pBR322 by chlorophyllin and possible mechanism (s) of action. Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis 425(1): 71–79. https://doi.org/10.1016/S0027-5107(98)00250-4
Lipshultz S, Scully R, Lipsitz S, Sallan S, Silverman L, Miller T, Barry E, Asselin B, Athale U and Clavell L. (2010). Assessment of dexrazoxane as a cardioprotectant in Doxorubicin-treated children with high-risk acute lymphoblastic leukaemia: Longterm follow-up of a prospective, randomised, multicentre trial. Lancet Oncology 11(10): 950–961. https://doi.org/10.1016/S1470-2045(10)70204-7
Maillet A, Tan K, Chai X, Sadananda S, Mehta A, Ooi J, Hayden M, Pouladi M, Ghosh S and Shim W. (2016). Modeling doxorubicin-induced cardiotoxicity in human pluripotent stem cell derived-cardiomyocytes. Scientific Reports 6: 1–13. https://doi.org/10.1038/srep25333
Maritim A, Sanders A and Watkins R J. (2003). Diabetes, oxidative stress, and antioxidants: A review. Journal of Biochemical and Molecular Toxicology 17(1): 24–38. https://doi.org/10.1002/jbt.10058
Minotti G, Menna P, Salvatorelli E, Cairo G and Gianni L. (2004). Anthracyclines: Molecular advances and pharmacologic developments in antitumor activity and cardiotoxicity. Pharmacological Reviews 56(2): 185–229. https://doi.org/10.1124/pr.56.2.6
Osawa T. (1994). Novel natural antioxidants for utilization in food and biological systems. Postharvest Biochemistry of Plant Food-Materials in the Tropics 1: 241–251.
Papasani M, Akula A and Kilari E. (2015). Evaluation of cardioprotective activity of wheat grass and bioenhancing property of cow urine (wheat grass fortified with cow urine) against Doxorubicin-induced cardiomyopathy. The FASEB Journal 29(s1): 785–711.
Pietrzak M, Wieczorek Z, Stachelska A and Darzynkiewicz Z. (2003). Interactions of chlorophyllin with acridine orange, quinacrine mustard and doxorubicin analyzed by light absorption and fluorescence spectroscopy. Biophysical Chemistry 104(1): 305–313. https://doi.org/10.1016/S0301-4622(02)00387-3
Pietrzak M, Wieczorek Z, Wieczorek J and Darzynkiewicz Z. (2006). The ‘interceptor’ properties of chlorophyllin measured within the three-component system: Intercalator–DNA–chlorophyllin. Biophysical Chemistry 123(1): 11–19. https://doi.org/10.1016/j.bpc.2006.03.018
Priya L B, Baskaran R, Huang C Y and Padma V V. (2017). Neferine ameliorates cardiomyoblast apoptosis induced by doxorubicin: possible role in modulating NADPH oxidase/ROS-mediated NF?B redox signaling cascade. Scientific Reports 7(1): 12283. https://doi.org/10.1038/s41598-017-12060-9
Reddy A, Harttig U, Barth M, Baird W, Schimerlik M, Hendricks J and Bailey G. (1999). Inhibition of dibenzo [a, l] pyrene-induced multi-organ carcinogenesis by dietary chlorophyllin in rainbow trout. Carcinogenesis 20(10): 1919–1926. https://doi.org/10.1093/carcin/20.10.1919
Salvatorelli E, Menna P and Minotti G. (2015). Managing anthracycline-induced cardiotoxicity: Beginning with the end in mind. Future Cardiology 11(4): 363–366. https://doi.org/10.2217/FCA.15.35
Satoh K and Butler W. (1978). Competition between the 735 nm fluorescence and the photochemistry of Photosystem I in chloroplasts at low temperature. Biochimica et Biophysica Acta, Bioenergetics 502(1): 103–110. https://doi.org/10.1016/0005-2728(78)90135-4
Singleton V and Rossi J. (1965). Colorimetry of total phenolics with phosphomolybdicphosphotungstic acid reagents. American Journal of Enology and Viticulture 16: 144–158.
Tebbi C, London W, Friedman D, Villaluna D, De Alarcon P, Constine L, Mendenhall N, Sposto R, Chauvenet A and Schwartz C. (2007). Dexrazoxane-associated risk for acute myeloid leukemia/myelodysplastic syndrome and other secondary malignancies in pediatric Hodgkin's disease. Journal of Clinical Oncology 25(5): 493–500. https://doi.org/10.1200/JCO.2005.02.3879
Thorn C, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein T and Altman R. (2011). Doxorubicin pathways: Pharmacodynamics and adverse effects. Pharmacogenetics and Genomics 21(7): 440–446. https://doi.org/10.1097/FPC.0b013e32833ffb56
Vrooman L, Neuberg D, Stevenson K, Asselin B, Athale U, Clavell L, Cole P, Kelly K, Larsen E and Laverdière C. (2011). The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: A report from the Dana-Farber Cancer Institute All Consortium. European Journal of Cancer 47(9): 1373–1379. https://doi.org/10.1016/j.ejca.2011.03.022
Wallace K. (2007). Adriamycin-induced interference with cardiac mitochondrial calcium homeostasis. Cardiovascular Toxicology 7(2): 101–107. https://doi.org/10.1007/s12012-007-0008-2
Wallin R and Arscott E. (1998). A practical guide to ISO 10993-5: Cytotoxicity. Medical Device and Diagnostics India 20: 96–98.