Abstract
This study aimed to correlate the oxidative stress marker levels in saliva with the clinical stage based on mouth opening, fibrotic bands and histopathological grades of oral submucous fibrosis (OSF) patients. The study included patients clinically diagnosed with OSF (n = 63) and equal number of age and gender matched controls. Patients with OSF were defined by mouth opening stage, fibrotic bands and histopathological grades. Unstimulated saliva from both control and OSF patients were analysed for oxidative markers like lipid peroxides (LPO), non-enzymic antioxidants [reduced glutathione (GSH), vitamin A, vitamin E, vitamin C] and enzymatic antioxidants [glutathione peroxidase (GPx), superoxide dismutase (SOD)] and correlated with different stages and grades. Total salivary protein and LPO were significantly increased in OSF group with no significant change in the levels of GSH compared to controls. In OSF patients, a significant decrease in the levels of vitamins A, C and E was observed. The activities of salivary SOD and GPx were significantly decreased in OSF patients compared to controls. These changes significantly correlated with the increasing and differing grades of OSF that reflects increased oxidative stress with the progress of OSF.
Similar content being viewed by others
References
Rajendran R. Oral submucous fibrosis. J Oral Maxillofac Pathol. 2003;7(1):1–4.
Hazare VK, Goel RR, Gupta PC. Oral submucous fibrosis, areca nut and pan masala use: a case-control study. Natl Med J India. 1998;11(6):299.
Amarasena N, Ekanayaka AN, Herath L, Miyazaki H. Association between smoking, betel chewing and gingival bleeding in rural Sri Lanka. J Clin Periodontol. 2003;30(5):403–8.
Angadi PV, Kale AD, Hallikerimath S. Evaluation of myofibroblasts in oral submucous fibrosis: correlation with disease severity. J Oral Pathol Med. 2011;40(3):208–13.
Chang YC, Yang SF, Tai KW, Chou MY, Hsieh YS. Increased tissue inhibitor of metalloproteinase-1 expression and inhibition of gelatinase A activity in buccal mucosal fibroblasts by arecoline as possible mechanisms for oral submucous fibrosis. Oral Oncol. 2002;38(2):195–200.
Rajalalitha P, Vali S. Molecular pathogenesis of oral submucous fibrosis: a collagen metabolic disorder. J Oral Pathol Med. 2005;34(6):321–8.
Ekanayaka RPTW. Oral submucous fibrosis: review on mechanisms of pathogenesis and malignant transformation. J Carcinog Mutagene. 2013;S5:002.
Stich HF, Anders F. The involvement of reactive oxygen species in oral cancers of betel quid/tobacco chewers. Mutat Res. 1989;214(1):47–61.
Sun Y. Free radicals, antioxidant enzymes, and carcinogenesis. Free Radic Biol Med. 1990;8(6):583–99.
Bourne GH, Kidder GW. Biochemistry and physiology of nutrition. Cambridge: Academic Press; 1953.
Malamud D. Saliva as a diagnostic fluid. Dent Clin N Am. 2011;55(1):159–78.
Miricescu D, Greabu M, Totan A, Didilescu A, Radulescu R. The antioxidant potential of saliva: clinical significance in oral diseases. Ther Pharmacol Clin Toxicol. 2011;2:139–43 (2011;XV(2)).
Miricescu D, Totan A, Calenic B, Mocanu B, Didilescu A, Mohora M, et al. Salivary biomarkers: relationship between oxidative stress and alveolar bone loss in chronic periodontitis. Acta Odontol Scand. 2014;72(1):42–7.
Al-Rawi NH. Diabetes, oxidative stress, antioxidants and saliva: a review. Rijeka: INTECH Open Access Publisher; 2012.
Khanna JN, Andrade NN. Oral submucous fibrosis: a new concept in surgical management. Report of 100 cases. Int J Oral Maxillofac Surg. 1995;24(6):433–9.
Haider SM, Merchant AT, Fikree FF, Rahbar MH. Clinical and functional staging of oral submucous fibrosis. Br J Oral Maxillofac Surg. 2000;38(1):12–5.
Pindborg JJ, Sirsat SM. Oral submucous fibrosis. Oral Surg Oral Med Oral Pathol. 1966;22(6):764–79.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–75.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.
Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582(1):67–78.
Bessey OA, Lowry OH, et al. The determination of vitamin A and carotene in small quantities of blood serum. J Biol Chem. 1946;166(1):177–88.
Emmerie A, Engel C. Colorimetric determination of tocopherol (Vitamin E): III. Estimation of tocopherol in blood-serum. Recl Trav Chim Pays Bas. 1939;58(10):895–902.
Roe JH, Kuether CA. The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenylhydrazine derivative of dehydroascorbic acid. J Biol Chem. 1943;147(2):399–407.
Kakkar P, Das B, Viswanathan PN. A modified spectrophotometric assay of superoxide dismutase. Indian J Biochem Biophys. 1984;21(2):130–2.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: biochemical role as a component of glutathione peroxidase. Science. 1973;179(4073):588–90.
Paissat DK. Oral submucous fibrosis. Int J Oral Surg. 1981;10(5):307–12.
Nair UJ, Floyd RA, Nair J, Bussachini V, Friesen M, Bartsch H. Formation of reactive oxygen species and of 8-hydroxydeoxyguanosine in DNA in vitro with betel quid ingredients. Chem Biol Interact. 1987;63(2):157–69.
Nater UM, Rohleder N. Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology. 2009;34(4):486–96.
Ball WD, Hand AR, Johnson AO. Secretory proteins as markers for cellular phenotypes in rat salivary glands. Dev Biol. 1988;125(2):265–79.
Krasteva AAE, Ivanova A, Altankova I, Bocheva T, Stanimirov P, Bobeva A, Janev N, Kisselova A. Salivary components of treated cancer patients and patients with precancerous lesions. J IMAB. 2008;14(2):41.
Dayem AA, Choi HY, Kim JH, Cho SG. Role of oxidative stress in stem, cancer, and cancer stem cells. Cancers. 2010;2(2):859–84.
Rai B, Kaur J, Jacobs R, Singh J. Possible action mechanism for curcumin in pre-cancerous lesions based on serum and salivary markers of oxidative stress. J Oral Sci. 2010;52(2):251–6.
Metkari S, Tupkari J, Barpande S. An estimation of serum malondialdehyde, superoxide dismutase and vitamin A in oral submucous fibrosis and its clinicopathologic correlation. J Oral Maxillofac Pathol. 2007;11(1):23–7.
Shetty SR, Babu SG, Kumari S, Rao V, Vijay R, Karikal A. Malondialdehyde levels in oral sub mucous fibrosis: a clinicopathological and biochemical study. N Am J Med Sci. 2012;4(3):125–8.
Gupta S, Reddy MV, Harinath BC. Role of oxidative stress and antioxidants in aetiopathogenesis and management of oral submucous fibrosis. Indian J Clin Biochem. 2004;19(1):138–41.
Khanna SS, Karjodkar FR. Circulating immune complexes and trace elements (copper, iron and selenium) as markers in oral precancer and cancer: a randomised, controlled clinical trial. Head Face Med. 2006;2:33.
Nagler RM, Klein I, Zarzhevsky N, Drigues N, Reznick AZ. Characterization of the differentiated antioxidant profile of human saliva. Free Radic Biol Med. 2002;32(3):268–77.
Amerongen AV, Veerman EC. Saliva—the defender of the oral cavity. Oral Dis. 2002;8(1):12–22.
Battino M, Ferreiro MS, Gallardo I, Newman HN, Bullon P. The antioxidant capacity of saliva. J Clin Periodontol. 2002;29(3):189–94.
Wong DY, Hsiao YL, Poon CK, Kwan PC, Chao SY, Chou ST, et al. Glutathione concentration in oral cancer tissues. Cancer Lett. 1994;81(2):111–6.
Chang YC, Huang FM, Tai KW, Yang LC, Chou MY. Mechanisms of cytotoxicity of nicotine in human periodontal ligament fibroblast cultures in vitro. J Periodontal Res. 2002;37(4):279–85.
Nordmann R, Ribière C. Superoxydedismutases: role biologique; espoir thérapeutique? Cah Nutr Diét. 1991;26(6):398–402.
Perluigi M, Butterfield DA. Oxidative stress and down syndrome: a route toward Alzheimer-like dementia. Curr Gerontol Geriatr Res. 2012;2012:724904.
Epperly MW, Carpenter M, Agarwal A, Mitra P, Nie S, Greenberger JS. Intraoral manganese superoxide dismutase-plasmid/liposome (MnSOD-PL) radioprotective gene therapy decreases ionizing irradiation-induced murine mucosal cell cycling and apoptosis. In Vivo. 2004;18(4):401–10.
Laszlo A, Matkovics B, Varge SI, Wittman T, Fazekas T. Changes in lipid peroxidation and antioxidant enzyme activity of human red blood cells after myocardial infarction. Clin Chim Acta. 1991;203(2–3):413–5.
Flohe L. The impact of thiol peroxidases on redox regulation. Free Radic Res. 2015;50(2):1–17.
Kumar A, Bagewadi A, Keluskar V, Singh M. Efficacy of lycopene in the management of oral submucous fibrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007;103(2):207–13.
Heber D, Bowerman S. Nutrition and cancer treatment. Handbook of nutrition and food. Boca Raton: CRC Press; 2001.
Geesin JC, Hendricks LJ, Falkenstein PA, Gordon JS, Berg RA. Regulation of collagen synthesis by ascorbic acid: characterization of the role of ascorbate-stimulated lipid peroxidation. Arch Biochem Biophys. 1991;290(1):127–32.
Hayes JD, McLellan LI. Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Radic Res. 1999;31(4):273–300.
Acknowledgements
The study was funded by Young Faculty Research Grant of Sri Ramachandra University (2010–2011).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Divyambika, C.V., Sathasivasubramanian, S., Vani, G. et al. Correlation of Clinical and Histopathological Grades in Oral Submucous Fibrosis Patients with Oxidative Stress Markers in Saliva. Ind J Clin Biochem 33, 348–355 (2018). https://doi.org/10.1007/s12291-017-0689-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12291-017-0689-7