Role of free radical scavengers in oral malignancies treated with radiotherapy
Keywords:Free radical scavengers, Malonyldialdehyde (MDA), Superoxide dismutase (SOD), Glutathione reductase (GR), Radiotherapy
Background: Radiotherapy has an important role in treatment of oral cancer, but it causes some deleterious effect on healthy cells. Radiation produces free radicals which cause lipo-peroxidation, alteration of protein, and DNA damage, and eventually cell death. This study is designed to evaluate protective role of antioxidants in oral malignancies treated with radiotherapy.
Methods: This study is conducted in patients of oral cancer treated with radiotherapy. Patients were divided into two groups, control (n=7) and test (n=9). Patients in control group treated with radiotherapy alone and in test group were supplemented with oral antioxidants throughout the radiotherapy course. Pre and post radiotherapy levels of MDA, SOD and Glutathione reductase were measured in blood and cancerous tissue in both groups and statistically compared. TNM staging before and after radiotherapy and side effects of radiotherapy were also compared in both groups.
Results: On statistical comparison of mean difference values of MDA, SOD & GR of control v/s test group, it was noticed that there was a significant reduction in MDA (p<0.05) and significant increase in GR levels (p<0.05) but non significant increase in SOD levels (p>0.05) in test group in comparison to control group for both blood and tissue levels. TNM status of patients improved significantly after radiotherapy in test group. Comparison of side effects between both groups indicated that there was reduction in side effects in test group after radiotherapy.
Conclusion: These findings indicated the protective role of antioxidants against free radicals produced in oral malignancies treated with radiotherapy.
Blot WJ, McLaughlin JK, Winn DM, Austin DF, Greenberg RS, Preston-Martin S et al. Smoking and drinking in relation to oral and pharyngeal cancer. Cancer Res. 1988 Jun 1; 48(11):3282-7.
Hashibe M, Brennan P, Chuang SC, et al. Interaction between tobacco and alcohol use and the risk of head and neck cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev 2009; 18:541-50.
Cummings CW, Fredrickson JM, Harker LA, et al. Otolaryngology - Head and Neck Surgery. Saint Louis, Mo: Mosby-Year Book, Inc, 1998.
Harrison LB, Sessions RB, Hong WK, eds.: Head and Neck Cancer: A Multidisciplinary Approach. Philadelphia, Pa: Lippincott-Raven, 1999.
Anderson TJ, Meredith IT, Yeung AC, Frei B, Selwyn AP, Ganz P. The effect of cholesterol-lowering and antioxidant therapy on endothelium-dependent coronary vasomotion. N Engl J Med. 1995 Feb 23; 332(8):488-93.
Sabitha KE, Shyamaladevi CS. Oxidant and antioxidant activity changes in patients with oral cancer and treated with radiotherapy. Oral Oncol 1999 May; 35(3):273-7.
Manoharan S, Kolanjiappan K, Suresh K, Panjamurthy K. Lipid peroxidation & antioxidants status in patients with oral squamous cell carcinoma. Indian J Med Res. 2005 Dec;122(6):529-34.
Subapriya R, Kumaraguruparan R, Ramachandran CR, Nagini S. Oxidant –Antioxidant status in patients with oral squamous cell carcinoma at different oral sites. Clin Biochem 2002; 35:489-93.
Upadhya S, Upadhya S, Krishna Mohan S. Oxidant – Antioxidant Status in colorectal cancer patients before and after treatment. Ind J Clin Biochem 2004; 19: 80-83.
Ohkawa H, Ohishi N & Yagi K. Assay for lipid peroxidase in animal tissue by thio-barbituric acid reaction. Anal Biochem 1979; 95:357-8.
Wooliams JA, Wiener G, Anderson PH, Mc Murray CH. Research veterinary science.1983; 34: 253-256.
Goldberg DM & Sponser RJ. In methods of enzymatic analysis (Bergmeyen H.V. Ed) 3rd ed: Verlog Chemie Deer field Beach, F.I. 1983; Vol.3, pp 258-265.
Chapman JD, Reuvers AP. The time scale of radioprotection in mammalian cells. Experientia Suppl. 1977; 27:9-18.
Quillen P. Adjuvant nutrition in cancer treatment. Am J Nat Med 1995; 2(5):8-14.
Demling RD. Glutamine and antioxidant replacement therapy after severe burn and trauma monograph. 1996
Goringe AP, Brown S, O'Callaghan U, Rees J, Jebb S, Elia M et al. Glutamine and vitamin E in the treatment of hepatic veno-occlusive disease following high dose chemotherapy. Bone Marrow Transplant 1998 Apr;21(8):829-32
Sabitha KE, Shyamaladevi CS. Oxidant and antioxidant activity changes in patient with oral cancer and treated with radiotherapy.Oral Oncol. 1999 May;35(3):273-7.
Sangeetha P, Das UN, Koratkar R, Suryaprabha P. Increase in free radical generation and lipid peroxidation following chemotherapy in patients with cancer. Free Radic Biol Med. 1990;8(1):15-9.
Anissa K Shariff, Sangita R Patil, Pramod S Shukla, Ajit V Sontakke, Anup S Hendre and Anand K Gudur. Effect of oral antioxidant supplementation on lipid peroxidation during radiotherapy in head and neck malignancies. Indian Journal of Clinical Biochemistry 2009; 24(3):307-11.
Wadleigh RG, Redman RS, Graham ML, Krasnow SH, Anderson A, Cohen MH. Vitamin E in the chemotherapy induced oral mucositis. Am J Med. 1992 May;92(5):481-4.
Nagler RM, Reznick AZ, Slavin S, Nagler A. Partial protection of rat parotid glands from irradiation-induced hyposalivation by manganese superoxide dismutase. Arch Oral Biol. 2000 Sep;45(9):741-7.
Hennekens CH. Micronutrients and cancer prevention. Cancer Det Prev 1984;7:147-58.
Machlin LJ, Bendich A. Free radical tissue damage: protective role of antioxidant nutrients. FASEB J. 1987 Dec;1(6):441-5.
Lamson DW, Brignall MS. Antioxidant in cancer therapy: their actions and interactions with oncologic therapies. Altern Med Rev. 1999 Oct;4(5): 304-29.
JM Jamison, HS Taper, J Gilloteaux, JL Summers. The in vivo anti-tumor activity of vitamin C, K3 combinations against human prostate cancer correlates with their abilities to reactivate ON ases. Presented at the sixth international symposium on predictive oncology and intervention strategies, Paris, 10th feb. 2002.
R. Bryan Bell, Deepak Kademani, Louis Homer, Eric J. Dierks, Bryce E. Potter. Tongue Cancer: Is There a Difference in Survival Compared With Other Subsites in the Oral Cavity? Journal of Oral and Maxillofacial Surgery. 2007 February; 65(2): 229-36.
S. R. Larsen, J. Johansen, J. A. Sørensen, A. Krogdahl. The prognostic significance of histological features in oral squamous cell carcinoma. Journal of Oral Pathology & Medicine. 2009 September; 38(8): 657–62.
Brouha XDR, Tromp DM, Hordijk G, Winnubst JAM, de Leeuw RJ. Oral and pharyngeal cancer: analysis of patient delay at different tumor stages. Head Neck 2005;27:939–45.
Blumenthal RD, Lew W, Reising A, Soyne D, Osorio L, Ying Z et al. Anti-oxidant vitamin reduces normal tissue toxicity induced by radio-immunotherapy. Int J Cancer. 2000 Apr 15;86(2): 276-80.