Malondialdehyde Level and Tissue Apoptosis Count as an Early-Detection Marker of Oral Potentially Malignant Disorders

Abstract

Objectives The malondialdehyde (MDA) level and TA count represent the progression of oral potentially malignant disorders (OPMD) to malignancy and thus may be used as an indicator of oral epithelial dysplasia (OED). This study aimed to determine the MDA level and tissue apoptosis (TA) count in oropharyngeal tissue of Wistar rats exposed to sidestream cigarette smoke.

Materials and Methods Wistar rats were divided into three groups: T4 group (4-week cigarette smoke exposure), T8 group (8-week cigarette smoke exposure), and control group, which was not exposed to cigarette smoke. The oropharyngeal tissue of the rats from each group was examined histopathologically to count the number of apoptotic cells, and then the blood serum was made to measure the MDA level.

Statistical Analysis Bonferroni test was performed to see the differences in each group for MDA level. While the data from tissue apoptosis were analyzed using Mann-Whitney U test for the significance. All data were considered significant if p < 0.05.

Results The MDA level and TA count increased as the duration of cigarette smoke exposure increased. In the T8 group, the MDA level and TA count were significantly higher compared with the T4 and control groups with a p-value < 0.05.

Conclusions Exposure to sidestream cigarette smoke increased the TA count and MDA level in the oropharyngeal tissue of Wistar rats. The TA count and MDA level may be used as markers of OPMD.

Keywords

tobacco addiction - apoptosis index - malondialdehyde - oral epithelial dysplasia - oral potentially malignant disorder - cancer

Publication History

Article published online:
18 April 2022

• References

• 1 Shield KD, Ferlay J, Jemal A. et al. The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin 2017; 67 (01) 51-64
• 2 Lee HW, Wang HT, Weng MW. et al. Cigarette side-stream smoke lung and bladder carcinogenesis: inducing mutagenic acrolein-DNA adducts, inhibiting DNA repair and enhancing anchorage-independent-growth cell transformation. Oncotarget 2015; 6 (32) 33226-33236
• 3 Cheng W, Zhou R, Feng Y, Wang Y. Mainstream smoke and sidestream smoke affect the cardiac differentiation of mouse embryonic stem cells discriminately. Toxicology 2016; 357-358: 1-10
• 4 Schick S, Shusterman DJ. Secondhand tobacco smoke exposure in humans. In: Morris JB, Shusterman DJ. eds. Toxicology of the Nose and Upper Airways. 1st ed.. Boca Raton: CRC Press; 2010: 14
• 5 Assi M. The differential role of reactive oxygen species in early and late stages of cancer. Am J Physiol Regul Integr Comp Physiol 2017; 313 (06) R646-R653
• 6 Donkena KV, Young CYF, Tindall DJ. Oxidative stress and DNA methylation in prostate cancer. Obstet Gynecol Int 2010; 2010: 302051
• 7 D'souza D, Subhas BG, Shetty SR, Balan P. Estimation of serum malondialdehyde in potentially malignant disorders and post-antioxidant treated patients: a biochemical study. Contemp Clin Dent 2012; 3 (04) 448-451
• 8 Nagler RM, Krayzler E, Veenman L, Gavish M. DNA fragmentation induced by cigarette smoke in oral cancer cells. Cancer Genomics Proteomics 2015; 12 (02) 77-81
• 9 Winkler J. Apoptosis and Inflammation. Basel, Switzerland: Birkhauser; 2012
• 10 Kuchino Y, Muller W. Progress in Molecular and Subcellular Biology: Apoptosis. Berlin: Springer; 2011
• 11 Kumar G. Orban's Oral Histology & Embryology. 14th ed.. New Delhi: Elsevier India; 2015
• 12 Kumar P, Clark M. Kumar & Clark's Clinical Medicine. 8th ed.. London: Elsevier; 2012
• 13 Koff JL, Ramachandiran S, Bernal-Mizrachi L. A time to kill: targeting apoptosis in cancer. Int J Mol Sci 2015; 16 (02) 2942-2955
• 14 Awadallah M, Idle M, Patel K, Kademani D. Management update of potentially premalignant oral epithelial lesions. Oral Surg Oral Med Oral Pathol Oral Radiol 2018; 125 (06) 628-636
• 15 Viswanathan V, Juluri R, Goel S, Madan J, Mitra SK, Gopalakrishnan D. Apoptotic index and proliferative index in premalignant and malignant squamous cell lesions of the oral cavity. J Int Oral Heal 2015; 7 (01) 40-43
• 16 Chole RH, Patil RN, Basak A, Palandurkar K, Bhowate R. Estimation of serum malondialdehyde in oral cancer and precancer and its association with healthy individuals, gender, alcohol, and tobacco abuse. J Cancer Res Ther 2010; 6 (04) 487-491
• 17 Prasetyaningtyas N, Jatiatmaja NA, Radithia D. et al. The response of the tongue epithelial on cigarette smoke exposure as a risk factor for oral cancer development. Eur J Dent 2021; 15 (02) 320-324
• 18 Bitla A, Reddy P, Sambasivaih K, Suchitra MM, Reddy VS, Rao PS. Evaluation of plasma malondialdehyde as a biomarker in patients with carcinoma of stomach. Biomed Res 2011; 22 (01) 63-68
• 19 Qebesy HS, Zakhary MM, Abd-alaziz MA, Ghany AAA, Qebesy HS. Tissue levels of oxidative stress markers and antixidants in breast cancer patients in relation to tumor grade. Al-Azhar Assiut Med J 2015; 13 (04) 10-17
• 20 Ayala A, Muñoz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev 2014; 2014: 360438
• 21 Rafiq R, Shah IA, Bhat GA. et al. Secondhand smoking and the risk of esophageal squamous cell carcinoma in a high incidence Region, Kashmir, India: a case-control-observational study. Medicine (Baltimore) 2016; 95 (01) e2340
• 22 Yu Z, Kastenmüller G, He Y. et al. Differences between human plasma and serum metabolite profiles. PLoS One 2011; 6 (07) e21230
• 23 Izzotti A, Balansky RM, Dagostini F. et al. Modulation of biomarkers by chemopreventive agents in smoke-exposed rats. Cancer Res 2001; 61 (06) 2472-2479
• 24 Wang G, Mohammadtursun N, Sun J. et al. Establishment and evaluation of a rat model of sidestream cigarette smoke-induced chronic obstructive pulmonary disease. Front Physiol 2018; 9 (58) 58
• 25 de Oliveira Semenzati G, de Souza Salgado B, Rocha NS, Michelin Matheus SM, de Carvalho LR, Garcia Martins RH. Histological and immunohistochemical study of the expression of p53 and ki-67 proteins in the mucosa of the tongue, pharynx and larynx of rats exposed to cigarette smoke. Inhal Toxicol 2012; 24 (11) 723-731
• 26 Kim DH, Suh YS, Mun KC. Tissue levels of malondialdehyde after passive smoke exposure of rats for a 24-week period. Nicotine Tob Res 2004; 6 (06) 1039-1042
• 27 Bello HA, Dandare A, Danmaliki GI. Effects of cigarette smoking on lipid peroxidation and serum antioxidant vitamins. IOSR J Pharm Biol Sci 2017; 12 (02) 40-44
• 28 Al-Serwi R, Elmeadawy S, Radwan L. Impact of passive smoke on tongue blood vessels, blood cell count and blood glutathione level (experimental study). EC Dent Sci 2015; 2 (06) 423-434
• 29 Schiavone S, Jaquet V, Trabace L, Krause KH. Severe life stress and oxidative stress in the brain: from animal models to human pathology. Antioxid Redox Signal 2013; 18 (12) 1475-1490
• 30 Yanxia J, Shi-Jie L, Junjie X, Xiaojing L, Juntao L. Effect of passive smoking on NO, GSH-pox, NOS, SOD, MDA in serum and lung homogenate of rats. Proceedings of the 2011 International Conference on Human Health and Biomedical Engineering, Jilin, China, August 19–12, 2011
• 31 Troy JD, Grandis JR, Youk AO, Diergaarde B, Romkes M, Weissfeld JL. Childhood passive smoke exposure is associated with adult head and neck cancer. Cancer Epidemiol 2013; 37 (04) 417-423
• 32 Xue J, Yang S, Seng S. Mechanisms of cancer induction by tobacco-specific NNK and NNN. Cancers (Basel) 2014; 6 (02) 1138-1156
• 33 Redza-Dutordoir M, Averill-Bates DA. Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 2016; 1863 (12) 2977-2992
• 34 Kesarwani P, Choudhary A, Gupta R. Apoptosis: a prognostic marker in oral epithelial dysplasia and oral squamous cell carcinoma. Int J Dent Heal Concerns 2016; 1 (02) 1-4
• 35 Rivlin N, Brosh R, Oren M, Rotter V. Mutations in the p53 tumor suppressor gene: Important milestones at the various steps of tumorigenesis. Genes Cancer 2011; 2 (04) 466-474
• 36 Ayuningtyas NF, Endah A, Permatasari A. The increase of dysplasia level in Wistar rats oropharyngeal mucosa exposed by sidestream cigarette smoke. Eur Asian J Biosci 2020; 14: 3641-3646
• 37 Nambiar S, Hegde V. Apoptosis in oral epithelial dysplastic lesions and oral squamous cell carcinoma: a prognostic marker. Indian J Pathol Microbiol 2016; 59 (03) 284-286
• 38 Pawar RB, Palaskar SJ, Kalavankar SS. Assessment of apoptotic index in various grades of oral epithelial dysplasia: a cross-sectional study. Indian J Pathol Microbiol 2020; 63 (04) 534-537