Document Type: Research(Original) Article
Department of Pharmacology, S. J. Thakkar Pharmacy College, Rajkot 360 005, Gujarat, India.
Myelotoxicity remains the most important cause of life threatening complications in patients undergoing antineoplastic chemotherapy cycles. Strategies to circumvent or lessen myelotoxicity may improve clinical outcome and quality of life in these patients. The aim of the present study is to investigate myeloprotective effect of Triticum aestivum Linn. (wheat) grass against chemotherapeutic agents induced bone marrow toxicity. Swiss albino mice were pretreated with wheatgrass juice at a dose of 20 ml/kg b.w. for 30 days. An hour after the last dose administration of WGJ, animals were injected with a single i.p. dose of cyclophosphamide (50 mg/kg b.w.) and doxorubicin (50 mg/kg b.w.). The reference drug amifostine (350 mg/kg b.w.) was administered 45 min prior to the cyclophosphamide and doxorubicin injection. At 24 h post chemotherapeutics challenge, animals were euthanized after blood sample collection and bone marrow was aspirated from both femurs. Hematologic parameters in blood samples were measured. Chromosomal abnormalities such as chromatid break, chromosomal ring, chromatid gap, chromatid exchange, chromosome break and number of micronucleated polymorphonuclear erythrocytes formed and polychromatic erythrocytes/normochromatic erythrocytes ratio were recorded in bone marrow smear. The results of present study show that pretreatment with wheatgrass juice significantly protected against cyclophosphamide and doxorubicin induced hematologic abnormalities and chromosomal damage in bone marrow stem cells due to its vast array of active principles. By virtue of its anticlastogenic and cytoprotective effects, wheatgrass juice might be considered as a promising candidate for adjuvant therapy without compromising efficacy of chemotherapeutic agents.
- Testart-Paillet D, Girard P, You B, Freyer G, Pobel C, Tranchand B. Contribution of modelling chemotherapy-induced hematological toxicity for clinical practice. Crit Rev Oncol Hematol. 2007;63:1â11.
- Dale DC, McCarter GC, Crawford J, Lyman GH. Myelotoxicity and dose intensity of chemotherapy: Reporting practices from randomized clinical trials. JNCCN J Natl Compr Cancer Netw. 2003;1(3):440â54.
- Daniel D, Crawford J. Myelotoxicity from chemotherapy. Semin Oncol. 2006;33:74â85.
- Hood LE. Chemotherapy in the elderly: supportive measures for chemotherapy-induced myelotoxicity. Clin J Oncol Nurs. 2003;7:185â90.
- Repetto L. Incidence and clinical impact of chemotherapy induced myelotoxicity in cancer patients: an observational retrospective survey. Crit Rev Oncol Hematol. 2009;72:170â9.
- Dale DC. Advances in the treatment of neutropenia. Curr Opin Support Palliat Care. 2009;3:207â12.
- Singbartl G. Adverse events of erythropoietin in long-term and in acute/short-term treatment. Clin Investig. 1994;72:S36-43.
- Trueman P. Prophylactic G-CSF in patients with early-stage breast cancer: a health economic review. Br J Cancer. 2009;101 Suppl:S15â7.
- Padalia S, Drabu S, Raheja I, Gupta A, Dhamija M. Multitude potential of wheatgrass juice (green blood): an overview. Chronicles Young Sci. 2010;1:23â8.
- Singh N, Verma P, Pandey BR.Therapeutic potential of organic triticum aestivum Linn. (wheat grass) in prevention and treatment of chronic diseases: an overview. Int J Pharm Sci Drug Res. 2012;4:10â4.
- Kothari S, Jain AK, Mehta SC, Tonpay SD. Hypolipidemic effect of fresh Triticum aestivum (wheat) grass juice in hypercholesterolemic rats. Acta Pol Pharm - Drug Res. 2011;68:291â4.
- Arya P, Kumar M. Chemoprevention by Triticum aestivum of mouse skin carcinogenesis induced by DMBA and croton oil - association with oxidative status. Asian Pacific J Cancer Prev. 2011;12:143â8.
- Hosseinimehr SJ, Azadbakht M, Abadi AJ. Protective effect of hawthorn extract against genotoxicity induced by cyclophosphamide in mouse bone marrow cells. Environ Toxicol Pharmacol. 2008;25:51â6.
- GÃ¼lkaÃ§ MD, Akpinar G, UstÃ¼n H, OzÃ¶n Kanli A. Effects of vitamin A on doxorubicin-induced chromosomal aberrations in bone marrow cells of rats. Mutagenesis. 2004;19:231â6.
- Ganasoundari A, Uma Devi P, Rao BSS. Enhancement of bone marrow radioprotection and reduction of WR-2721 toxicity by Ocimum sanctum. Mutat Res - Fundam Mol Mech Mutagen. 1998;397:303â12.
- Ghai C. A text book of practical physiology. 8th ed. Jaypee Brothers Medical Publishers (P) Ltd; 2013. p. 34-69.
- Giri S, Sharma GD, Giri a, Prasad SB. Fenvalerate-induced chromosome aberrations and sister chromatid exchanges in the bone marrow cells of mice in vivo. Mutat Res. 2002;520:125â32.
- Patlolla BP, Patlolla AK, Tchounwou PB. Cytogenetic effects of 1,1-dichloroethane in mice bone marrow cells. Int. J. Environ. Res. Public Health. 2005;2:101â6.
- Tripathi P, Patel RK, Tripathi R, Kanzariya NR. Investigation of antigenotoxic potential of Syzygium cumini extract (SCE) on cyclophosphamide-induced genotoxicity and oxidative stress in mice. Drug Chem Toxicol. 2013;36:396â402.
- Aquino I, Perazzo FF, Maistro EL. Genotoxicity assessment of the antimalarial compound artesunate in somatic cells of mice. Food Chem Toxicol. 2011;49:1335â9.
- Carey PJ. Drug-induced myelosuppression: diagnosis and management. Drug Saf. 2003;26:691â706.
- Maxwell MB, Maher KE. Chemotherapy-induced myelosuppression. Semin Oncol Nurs. 1992;8:113â23.
- Kurtin S. Myeloid toxicity of cancer treatment. J Adv Pr Oncol. 2012;3:209â24.
- Senthilkumar S, Devaki T, Manohar BM, Babu MS. Effect of squalene on cyclophosphamide-induced toxicity. Clin Chim Acta. 2006;364:335â42.
- Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology. 2010;115:155â62.
- Quiles JL, Huertas JR, Battino M, Mataix J, Ramirez-Tortosa MC. Antioxidant nutrients and adriamycin toxicity. Toxicology. 2002;180:79â95.
- Guest I, Uetrecht J. Drugs toxic to the bone marrow that target the stromal cells. Immunopharmacology. 2000;46:103â12.
- Hogle W. Cytoprotective agents used in the treatment of patients with cancer. Semin Oncol Nurs. 2007;23:213â24.
- Santini V, Giles FJ. The potential of amifostine: From cytoprotectant to therapeutic agent. Haematologica. 1999;84:1035â42.
- Rades D, Fehlauer F, Bajrovic A, Mahlmann B, Richter E, Alberti W. Serious adverse effects of amifostine during radiotherapy in head and neck cancer patients. Radiother Oncol. 2004;70:261â4.
- Valeyrie-Allanore L, Poulalhon N, Fagot JP, Sekula P, Davidovici B, Sidoroff A, et al. Stevens-Johnson syndrome and toxic epidermal necrolysis induced by amifostine during head and neck radiotherapy. Radiother Oncol. 2008;87:300â3.
- Chen T, Shen M, Deng Z, Yang Z, Zhao R, Wang L, et al. A herbal formula, SYKT, reverses doxorubicin-induced myelosuppression and cardiotoxicity by inhibiting ROS-mediated apoptosis. Mol Med Rep. 2017;15:2057â66.
- Singh A, Kaur M, Choudhary A, Kumar B. Effect of Butea monosperma leaf extracts on cyclophosphamide induced clastogenicity and oxidative stress in mice. Pharmacognosy Res. 2015;7:85â91.
- Kukreja A, Wadhwa N, Tiwari A. Therapeutic role of natural agents in beta-thalassemia: A review. J Pharm Res. 2013;6:954â9.
- Marawaha RK, Bansal D, Kaur S, Trehan A. Wheat grass juice reduces transfusion requirement in patients with thalassemia major: a pilot study. Indian Pediatr. 2004;41:716â20.
- Fenech M. The micronucleus assay determination of chromosomal level DNA damage. Methods Mol Biol. 2008;410:185â216.
- Hayashi M. The micronucleus test-most widely used in vivo genotoxicity test. Genes Environ. 2016;38:18.
- Doherty AT. The in vitro micronucleus assay. Methods Mol. Biol., vol. 817, 2012, p. 121â41.
- Zaizuhana S, Puteri J Noor MB, Noralâashikin Y, Muhammad H, Rohana AB, Zakiah I. The in vivo rodent micronucleus assay of Kacip Fatimah (Labisia pumila) extract. Trop Biomed. 2006;23:214â9.
- ICH. International Conference on Harmonisation; guidance on S2(R1) Genotoxicity Testing and Data Interpretation for Pharmaceuticals intended for Human Use; availability. Notice. Fed Regist. 2012;77(110):33748â9.
- Molyneux G, Andrews M, Sones W, York M, Barnett A, Quirk E, et al. Haemotoxicity of busulphan, doxorubicin, cisplatin and cyclophosphamide in the female BALB/c mouse using a brief regimen of drug administration. Cell Biol Toxicol. 2011;27:13â40.
- Bingol G, Gulkac MD, Dillioglugil MO, Polat F, Kanli AO. Effect of resveratrol on chromosomal aberrations induced by doxorubicin in rat bone marrow cells. Mutat Res Genet Toxicol Env Mutagen. 2014;766:1â4.
- Duthie SJ, Dobson VL. Dietary flavonoids protect human colonocyte DNA from oxidative attack in vitro. Eur J Nutr. 1999;38:28â34.
- Mesbah L, Fillastre JP. Role of flavonoids in the prevention of haematotoxicity due to chemotherapeutic agents. HAEMA. 2004;7:313â20.
- Zhang QH, Wu CF, Duan L, Yang JY. Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells. Food Chem Toxicol. 2008;46:293â302.
- Cao J, Han J, Xiao H, Qiao J, Han M. Effect of tea polyphenol compounds on anticancer drugs in terms of anti-tumor activity, toxicology, and pharmacokinetics. Nutrients. 2016;8(12):762.