Author(s):
Akheruz Z. Ahmed, Prakashchandra Shetty, Shakta M. Satyam, Melanie Rose D’Souza, Archana M Herle, Varun K. Singh
Email(s):
varun.singh@manipal.edu
DOI:
10.52711/0974-360X.2021.00788 
Address:
Akheruz Z. Ahmed1, Prakashchandra Shetty2, Shakta M. Satyam3, Melanie Rose D’Souza4, Archana M Herle5, Varun K. Singh6
1,2,4Department of Anatomy, Melaka Manipal Medical College (Manipal Campus, Manipal Academy of Higher Education, Manipal - 576104, Karnataka (India).
3Assistant Professor, Department of Pharmacology, Melaka Manipal Medical College (Manipal Campus), Manipal Academy of Higher Education, Manipal - 576104, Karnataka (India).
5Department of Physiology, Melaka Manipal Medical College (Manipal Campus), Manipal Academy of Higher Education, Manipal - 576104, Karnataka (India).
6Department of Pathology, Melaka Manipal Medical College (Manipal Campus), Manipal Academy of Higher Education, Manipal - 576104, Karnataka (India).
*Corresponding Author
Published In:
Volume - 14,
Issue - 9,
Year - 2021
ABSTRACT:
Myelosuppression by doxorubicin is a life-threatening adverse effect in cancer patients undergoing chemotherapy. Methyl gallate is an antioxidant found in a variety of plant species. The study aimed to demonstrate the protective role of methyl gallate on doxorubicin-induced cytopenias in Wistar rats. The animals were prophylactically treated with two different doses of methyl gallate (150mg/kg/day and 300mg/kg/day) orally for seven days. Doxorubicin (25mg/kg; single dose) was administered through intraperitoneal route on the seventh day to induce cytopenias. Blood was collected 24 hours after the administration of doxorubicin and complete blood counts were estimated. There was significant (p=0.05) development of peripheral cytopenias in doxorubicin treated control rats compared to normal saline treated control rats. Methyl gallate at both the doses significantly (p=0.05) mitigated doxorubicin induced cytopenias compared to doxorubicin treated control rats. The findings of the present study revealed that methyl gallate has protective role in doxorubicin-induced cytopenias in Wistar rats. Following clinical studies, methyl gallate may serve as a viable alternative to growth factors in patients undergoing chemotherapy.
Cite this article:
Akheruz Z. Ahmed, Prakashchandra Shetty, Shakta M. Satyam, Melanie Rose D’Souza, Archana M Herle, Varun K. Singh. Methyl Gallate Mitigates Doxorubicin-Induced Peripheral Cytopenias: A Preclinical Experimental Study. Research Journal of Pharmacy and Technology. 2021; 14(9):4529-4. doi: 10.52711/0974-360X.2021.00788
Cite(Electronic):
Akheruz Z. Ahmed, Prakashchandra Shetty, Shakta M. Satyam, Melanie Rose D’Souza, Archana M Herle, Varun K. Singh. Methyl Gallate Mitigates Doxorubicin-Induced Peripheral Cytopenias: A Preclinical Experimental Study. Research Journal of Pharmacy and Technology. 2021; 14(9):4529-4. doi: 10.52711/0974-360X.2021.00788 Available on: https://rjptonline.org/AbstractView.aspx?PID=2021-14-9-2
REFERENCES:
1. Carvalho C, Santos RX, Cardoso S, Correia S, Oliveira PJ, Santos MS, Moreira PI. Doxorubicin: the good, the bad and the ugly effect. Current Medicinal Chemistry. 2009; 16(25): 3267-85.
2. Das S, Filippone SM, Williams DS, Das A, Kukreja RC. Beet root juice protects against doxorubicin toxicity in cardiomyocytes while enhancing apoptosis in breast cancer cells. Molecular and Cellular Biochemistry. 2016; 421(1-2): 89-101.
3. Chen T, Shen HM, Deng ZY, Yang ZZ, Zhao RL, Wang L, Feng ZP, Liu C, Li WH, Liu ZJ. A herbal formula, SYKT, reverses doxorubicin induced myelosuppression and cardiotoxicity by inhibiting ROS mediated apoptosis. Molecular Medicine Reports. 2017; 15(4): 2057-66.
4. Hajra S, Patra AR, Basu A, Bhattacharya S. Prevention of doxorubicin (DOX)-induced genotoxicity and cardiotoxicity: Effect of plant derived small molecule indole-3-carbinol (I3C) on oxidative stress and inflammation. Biomedicine and Pharmacotherapy. 2018; 101: 228-43.
5. Pizzo PA. Granulocytopenia and cancer therapy: past problems, current solutions, future challenges. Cancer. 1984; 54(S2): 2649-61.
6. Bloom JC, Brandt JT. Toxic responses of the blood. In: Klassen CD, ed. Casarett and Doull’s Toxicology Basic Science of Poisons. New York: Mc Graw Hill. 2008; 70(4): 455-84.
7. Lee MY, Bae ON, Chung SM, Kang KT, Lee JY, Chung JH. Enhancement of platelet aggregation and thrombus formation by arsenic in drinking water: a contributing factor to cardiovascular disease. Toxicology and applied pharmacology. 2002; 179(2): 83-8.
8. Vadhan-Raj S, Patel S, Bueso-Ramos C, Folloder J, Papadopolous N, Burgess A. Importance of Pre d0sing of Recombinant Human Thrombopoietin to Reduce Chemotherapy-Induced Early Thrombocytopenia. Journal of Clinical Oncology. 2003; 21(16): 3158-67.
9. Danesi R, Fogli S, Gennari A, Conte P, Del Tacca M. Pharmacokinetic-pharmacodynamic relationships of the anthracycline anticancer drugs. Clinical Pharmacokinetics. 2002; 41(6): 431-44.
10. Pommier Y, Leo E, Zhang H, Marchand C. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chemistry and Biology. 2010; 17(5): 421-33.
11. Singal P, Li T, Kumar D, Danelisen I, Iliskovic N. Adriamycin-induced heart failure: mechanisms and modulation. Molecular and cellular biochemistry. 2000; 207(1-2): 77-86.
12. Parker MA, King V, Howard KP. Nuclear magnetic resonance study of doxorubicin binding to cardiolipin containing magnetically oriented phospholipid bilayers. Biochimica et Biophysica Acta (BBA)-Biomembranes. 2001; 1514(2): 206-16.
13. Kuznetsov AV, Margreiter R, Amberger A, Saks V, Grimm M. Changes in mitochondrial redox state, membrane potential and calcium precede mitochondrial dysfunction in doxorubicin-induced cell death. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research. 2011; 1813(6): 1144-52.
14. Arya B, Krishnaveni K, Sambathkumar R. Review on Antioxidant Supplements use in Cancer Chemotherapy. Research Journal of Pharmacology and Pharmacodynamics. 2020; 12(1): 21-24.
15. Saha D, Tamrakar A. Xenobiotics, Oxidative Stress, Free Radicals Vs. Antioxidants: Dance Of Death to Heaven's Life. Asian Journal of Research in Pharmaceutical Science. 2011; 1(2): 36-38.
16. Shivhare Y, Singh P, Gadekar R, Soni P. Botanicals as antioxidants: A renovate review. Research Journal of Pharmacognosy and Phytochemistry. 2010; 2(4): 255-59.
17. Sahu P, Sahu K, Dubey RD, Chatterjee S, Chatterjee T. Herbal Antioxidants: A Review. Research Journal of Pharmacognosy and Phytochemistry. 2010; 2(6): 434-36.
18. Jaydeokar AV, Bandawane DD, Nipate SS, Chaudhari PD. Natural antioxidants: a review on therapeutic applications. Research Journal of Pharmacology and Pharmacodynamics. 2012;4(1): 55-61.
19. Patel RN, Patel UY, Sen DJ. Polyphenol antioxidants of green tea as free radical scavengers in green heart nanotechnology. Research Journal of Science and Technology. 2010 Oct 28; 2(5): 89-94.
20. Chakraborty P, Kumar S, Dutta D, Gupta V. Role of antioxidants in common health diseases. Research Journal of Pharmacy and Technology. 2009; 2(2): 238-44.
21. Menon R. Antioxidants and their Therapeutic Potential-A Review. Research Journal of Pharmacy and Technology. 2013; 6(12):1426-29.
22. Das TT. Role of Antioxidants in Health and Diseases-A Review. Research Journal of Pharmacy and Technology. 2015; 8(8):1033-37.
23. Suja C, Shuhaib B, Khathoom H, Simi K. A Review on Dietary Antioxidants. Research Journal of Pharmacy and Technology. 2016; 9(2):196-02.
24. Kang MS, Jang HS, Oh JS, Yang KH, Choi NK, Lim HS, Kim SM. Effects of methyl gallate and gallic acid on the production of inflammatory mediators interleukin-6 and interleukin-8 by oral epithelial cells stimulated with Fusobacterium nucleatum. The Journal of Microbiology. 2009; 47(6): 760-67.
25. Correa LB, Pádua TA, Seito LN, Costa TE, Silva MA, Candéa AL, Rosas EC, Henriques MG. Anti-inflammatory effect of methyl gallate on experimental arthritis: Inhibition of neutrophil recruitment, production of inflammatory mediators, and activation of macrophages. Journal of Natural Products. 2016; 79(6): 1554-66.
26. Hsieh TJ, Liu TZ, Chia YC, Chern CL, Lu FJ, Chuang MC, Mau SY, Chen SH, Syu YH, Chen CH. Protective effect of methyl gallate from Toona sinensis (Meliaceae) against hydrogen peroxide-induced oxidative stress and DNA damage in MDCK cells. Food and Chemical Toxicology. 2004; 42(5): 843-50.
27. Crispo JA, Piché M, Ansell DR, Eibl JK, Tai IT, Kumar A, Ross GM, Tai TC. Protective effects of methyl gallate on H2O2-induced apoptosis in PC12 cells. Biochemical and Biophysical Research Communications. 2010; 393(4): 773-78.
28. Khurana S, Hollingsworth A, Piche M, Venkataraman K, Kumar A, Ross GM, Tai TC. Antiapoptotic actions of methyl gallate on neonatal rat cardiac myocytes exposed to H2O2. Oxidative Medicine and Cellular Longevity. 2014; Article ID 657512:1-9..
29. Rahman N, Jeon M, Kim YS. Methyl gallate, a potent antioxidant inhibits mouse and human adipocyte differentiation and oxidative stress in adipocytes through impairment of mitotic clonal expansion. Biofactors. 2016; 42(6): 716-26.
30. Oidovsambuu S, Kim CY, Kang K, Dulamjav B, Jigjidsuren T, Nho CW. Protective effect of Paeonia anomala extracts and constituents against tert-butylhydroperoxide-induced oxidative stress in HepG2 cells. Planta Medica. 2013; 29(02): 116-22.
31. Hui MK, Wu WK, Shin VY, So WH, Cho CH. Polysaccharides from the root of Angelica sinensis protect bone marrow and gastrointestinal tissues against the cytotoxicity of cyclophosphamide in mice. International Journal of Medical Sciences. 2006; 3(1): 1.
32. Zhu W, Shou W, Payne RM, Caldwell R, Field LJ. A mouse model for juvenile doxorubicin-induced cardiac dysfunction. Paediatric Research. 2008; 64(5): 488-94.
33. Fu X, Kong L, Tang M, Zhang J, Zhou X, Li G, Wang H, Fu F. Protective effect of ocotillol against doxorubicin induced acute and chronic cardiac injury. Molecular Medicine Reports. 2014; 9(1): 360-4.
34. Capo G, Waltzman R. Managing hematologic toxicities. The journal of supportive oncology. 2004; 2(1): 65.
35. Butt Z, Cella D. Relationship of hemoglobin, fatigue, and quality of life in anemic cancer patients. InRecombinant Human Erythropoietin (rhEPO) in Clinical Oncology 2008; 369-391.
36. Lind M, Vernon C, Cruickshank D, Wilkinson P, Littlewood T, Stuart N, Jenkinson C, Grey-Amante P, Doll H, Wild D. The level of haemoglobin in anaemic cancer patients correlates positively with quality of life. British Journal of Cancer. 2002; 86(8): 1243-9.
37. Wu Y, Aravind S, Ranganathan G, Martin A, Nalysnyk L. Anemia and thrombocytopenia in patients undergoing chemotherapy for solid tumors: a descriptive study of a large outpatient oncology practice database, 2000–2007. Clinical Therapeutics. 2009; 31: 2416-32.
38. Pizzo PA. Granulocytopenia and cancer therapy: past problems, current solutions, future challenges. Cancer. 1984; 54(S2): 2649-61.
39. Coffee C, Roush JK, Higginbotham ML. Carboplatin‐Induced Myelosuppression As Related To Body Weight In Dogs. Veterinary and Comparative Oncology. 2020.
40. Kim EJ, Lim KM, Kim KY, Bae ON, Noh JY, Chung SM, Shin S, Yun YP, Chung JH. Doxorubicin‐induced platelet cytotoxicity: a new contributory factor for doxorubicin‐mediated thrombocytopenia. Journal of Thrombosis and Haemostasis. 2009; 7(7): 1172-83
41. Sachdev R, Tiwari AK, Goel S, Raina V, Sethi M. Establishing biological reference intervals for novel platelet parameters (immature platelet fraction, high immature platelet fraction, platelet distribution width, platelet large cell ratio, platelet-X, plateletcrit, and platelet distribution width) and their correlations among each other. Indian Journal of Pathology and Microbiology. 2014; 57(2): 231.
42. Zhang S, Cui YL, Diao MY, Chen DC, Lin ZF. Use of platelet indices for determining illness severity and predicting prognosis in critically ill patients. Chinese Medical Journal. 2015; 128(15): 2012.
43. Goldberg GL, Gibbon DG, Smith HO, et al. Clinical impact of chemotherapy-induced thrombocytopenia in patients with gynecologic cancer. J Clin Oncol. 1994; 12: 2317–20.
44. Liou SY, Stephens JM, Carpiuc KT, Feng W, Botteman MF, Hay JW. Economic burden of haematological adverse effects in cancer patients. Clinical Drug Investigation. 2007; 27(6): 381-96.
45. Kim EJ, Lim KM, Kim KY, Bae ON, Noh JY, Chung SM, Shin S, Yun YP, Chung JH. Doxorubicin‐induced platelet cytotoxicity: a new contributory factor for doxorubicin‐mediated thrombocytopenia. Journal of Thrombosis and Haemostasis. 2009; 7(7): 1172-83.
46. Kluza J, Marchetti P, Gallego MA, Lancel S, Fournier C, Loyens A, Beauvillain JC, Bailly C. Mitochondrial proliferation during apoptosis induced by anticancer agents: effects of doxorubicin and mitoxantrone on cancer and cardiac cells. Oncogene. 2004; 23(42): 7018-30.
47. Afanasev I. Detection of superoxide in cells, tissues and whole organisms. Frontiers in Bioscience (Elite Edition). 2009 Jun 1; 1: 153-60.
48. Whang WK, Park HS, Ham I, Oh M, Namkoong H, Kim HK, Hwang DW, Hur SY, Kim TE, Park YG, Kim JR. Methyl gallate and chemicals structurally related to methyl gallate protect human umbilical vein endothelial cells from oxidative stress. Experimental and Molecular Medicine. 2005; 37(4): 343-52.
49. Lee SH, Kim JK, Kim DW, Hwang HS, Eum WS, Park J, Han KH, Oh JS, Choi SY. Antitumor activity of methyl gallate by inhibition of focal adhesion formation and Akt phosphorylation in glioma cells. Biochimica et Biophysica Acta (BBA)-General Subjects. 2013; 1830(8): 4017-29.
50. Cho EJ, Yokozawa T, Rhyu DY, Kim SC, Shibahara N, Park JC. Study on the inhibitory effects of Korean medicinal plants and their main compounds on the 1, 1-diphenyl-2-picrylhydrazyl radical. Phytomedicine. 2003; 10(6-7): 544-51.