Metabolic Antioxidant Status in Oral Squamous Cell Carcinoma
F. Mariyam Niyas1, Savitha G.2
1Undergraduate Student, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Chennai, India
2Senior Lecturer, Department of Biochemistry, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences.
*Corresponding Author E-mail: marlog7494@gmai.com, drsavitha80@gmail.com
ABSTRACT:
Aim and Background: Oral Squamous cell Carcinoma (OSCC) represents the sixth most common cancer, accounting for 2-4% of all malignancies worldwide. Overall survival rate is less than 60%. OSCC is 2 to 3 times more prevalent in men than women. Important cause for this cancer is toxicity produced by the Reactive Oxygen Species (ROS). Elimination of this ROS helps to prevent the prognosis of the disease. This elimination is done by Antioxidants. There were very few studies on metabolic antioxidant status in OSCC. So, aim of this study was to estimate the level of metabolic antioxidants (Uric acid and Bilirubin) in OSCC patients and assess their role on prevention of the disease. Method and Materials: The study group included 25 OSCC patients and 25 age and sex matched healthy subjects as a control group. Serum uric acid and Bilirubin were analysed byUricase and Diazomethod respectively Using ERBA CHEM 5Plus Analyser. Statistical analysis was performed using Student T Test. P<0.05 was considered to be significant. Result: The mean serum Uric acid level in study and control groups were 3.50±0.93 and 5.8±0.84 respectively. The mean serum Bilirubin level in study and control groups were 0.26±0.16 and 0.57±0.23 respectively. These levels were low in the study group when compared to the control group with the significant p value of 0.0001. Conclusion: In OSCC, due to excessive production of ROS, the uric acid and Bilirubin levels were reduced. So assessment of these levels may helpful to assess the prognosis of the disease and select the proper therapeutic options.
KEYWORDS: Oral squamous cell carcinoma, metabolic antioxidants, uric acid, bilirubin.
INTRODUCTION:
Oral Squamous Cell Carcinoma (OSCC) represents 95% of all forms of head and neck cancer and over the last decade its incidence has increased by 50%[1]. OSCC is considered to be a preventable condition, due to the possibility of early detection and treatment[2]. It is a potentially malignant neoplasia which arises on the lip and oral cavity[3]. While OSCC may arise de novo, it may be preceded by the presence of clinically visible changes of oral mucosa, which have potential for malignant transformation, these lesions are together categorized as potentially malignant disorders[4].
The major causes or risk factors of the OSCC are tobacco consumption, Betel quid chewing with ingredients like areca nut, slaked lime and tobacco, Alcohol consumption, Use of mouth wash, Viral infection by Epstein Barr Virus, Human Papilloma Virus, and Herpes simplex virus, Fungal infections by Candida Albicans, Immunosuppression, Individual with poor oral hygiene, Exposure to ionizing radiation, Syphilis, Occupational risk and Mate[5,6,7].
Major pathogenesis for development of oral cancer is excessive production of Reactive oxygen Species (ROS) like Superoxide radicals, hydroxyl radicals and hydrogen peroxide. ROS cause DNA base alterations, strand breaks, damage to tumour suppressor genes and enhanced expression of proto-oncogenes[8]. These ROS are neutralized by antioxidant defense mechanisms in mammalian cells. Thus antioxidants help in preventing disease and further progression of the disease.
Antioxidants are substances that can eliminate reactive oxygen species directly or indirectly or inhibit the production of reactive oxygen species[9]. Antioxidants can be divided into two groups Enzymatic and Non enzymatic. Enzymatic antioxidants include Superoxide dismutase (SOD), Glutathione Peroxidase (GPx), Catalase (CAT). The non enzymatic antioxidant includes glutathione, Vitamin C, VitaminE, carotenoids, Uric acid, Albumin, Bilirubin and so on[10]. Non enzymatic antioxidants can be divided into nutrient antioxidant and metabolic antioxidant. Nutrient antioxidants are exogenous antioxidants which cannot be synthesized in the body. But they provided via diet like trace elements (selenium, manganese, zinc), flavonoids, omega-3 and omega-6 fatty acids etc.
Metabolic antioxidants are the endogenous antioxidants, which are produced by metabolism in the body like lipoic acid, glutathione, L-arginine, co enzymes Q10, melatonin, uric acid, Bilirubin and metal chelating proteins[11,12]. There were very few studies on metabolic antioxidant role in OSCC. So, aim of the current study was to assess the level and role of metabolic antioxidants like uric acid and Bilirubin in OSCC patients.
MATERIALS AND METHODS:
50 Patients were selected from those attending the out patient department of Saveetha Dental College, and hospitals and divided into two groups as follows
Group I–25 age and sex matched healthy individuals
Group II–25 Patients with Oral Squamous Cell Carcinoma
Inclusion Criteria:
· Healthy individuals
· Initial stage of Oral Squamous Cell Carcinoma Patients
Exclusion Criteria:
Persons with other systemic illness like cardio vascular disease, renal failure, Stroke, endocrine illness.
· Persons with acute illness like fever.
· Immunocompromisedpersons.
· Chronic alcoholics, Smokers
· Persons with other liver disorders ormalignancies.
Sample collection:
Informed consent was obtained from the patients before sample collection. 5 ml of venous blood was collected in plain collection tubes and centrifuged in 3000rpm. Then serum was separated and analysed to estimate the Serum Uric acid and Bilirubin by Uricase andDiazomethod respectively using ERBA CHEM 5 plus analyser.
RESULTS:
All the data were analysed by using SPSS software. Student t test analysis was done to find out significant differences between the two groups. All the tests were considered significant at p<0.05 level.
Table 1: Mean, SD, p Values ofUric acid in two groups
|
Uric Acid |
Mean |
SD |
p value |
|
Control |
5.8 |
0.84 |
0.0001 |
|
OSCC |
3.5 |
0.93 |
Figure 1: Mean Uric Acid levels in two groups
Table 2: Mean, SD, p Values of Bilirubin in two groups
|
Bilirubin |
Mean |
SD |
p value |
|
Control |
0.26 |
0.57 |
0.0001 |
|
OSCC |
0.16 |
0.23 |
Figure 2: Mean Bilirubin levels in two groups
DISCUSSION:
The results of this study revealed that there is a significant difference in mean uric acid and bilirubin levels of the normal healthy individuals and OSCC patients.
The mean serum Uric acid level in study and control groups were 3.50±0.93 and 5.8±0.84 respectively (Table 1, Figure 1). The mean serum Bilirubin level in study and control groups were 0.26±0.16 and 0.57±0.23 respectively (Table 2, Figure 2). These levels were low in the study group when compared to the control group with the significant p value of 0.0001.
Uric acid has been considered to be an important antioxidant and free radical scavenger in human[13]. Uric acid is generated by the metabolism of purine in most mammals[14]. It is formed in the xanthine and hypoxanthine reactions catalysed by xanthine Oxidase. Uric acid is the powerful scavenger of free radicals that provide 60% of free radical scavenging capacity in plasma. It scavenges singlet oxygen, peroxy radicals and hydroxy radicals[15,16]. Uric acid interacts with peroxynitrite to form a stable nitric oxide donor, thus promoting vasodilatation and reducing the potential for peroxynitrite induced oxidative damage[17]. Approximately, about 1/3rd of uric acid in the body is excreted via urine and intestinal secretion. Due to increased production of ROS in OSCC, the metabolic antioxidant like uric cid level was reduced in these patients.
Bilirubin is formed in cells by the two sequential reactions, catalysed by hemeoxygenease and biliverdinreductase. It presents in various chemical forms in blood, namely conjugated with glucuronic acid (Direct Bilirubin) and Unconjugated (free bilirubin)[17]. Bilirubin has antioxidant and anti-inflammatory activity [18,19]. Bilirubin is considered to be the final product of heme catabolism. It neutralize the free radicals and prevent peroxidation of lipids[20,21]. Thus scavenges the peroxyl radicals as efficiently as alpha tocopherol[22].
CONCLUSION:
Because of powerful antioxidant capacity, Uric acid and bilirubin scavenge the reactive oxygen species and protect from our body from disease. In OSCC, due to excessive production of ROS, the uric acid and bilirubin levels were reduced. So assessment of these levels may helpful to assess the prognosis of the disease and select correct therapeutic option to treat the disease.
REFERENCES:
1. Cesar Rivera, Bernardo Venegas. Histological and Molecular aspects of Oral Squamous Cell Carcinoma (Review). ONCOL Lett. 2014; 8 (1): 7-11.
2. Bray F, Sankila R, Ferlay J, parkin D M. Estimates of cancer incidence and mortality in Europe in 1995. Eur J Cancer. 2002; 38: 99-166.
3. Cesar Rivera. Essentials of Oral Cancer. Int J ClinExpPathol. 2015; 8(9): 11884-11894.
4. GokulSridharan, PratibhaRamani, SangeetaPatankar. Serum metabolomics in oral leaukoplakia and oral squamous cell carcinoma. Journal of Cancer research and Therapeutics. 2018; 13 (3): 556-561.
5. Malay Kumar, RonakNanavati, TapanG Modi, ChintanDobariya. Etiology and Risk factors: A Review. Oral Cancer. 2016; 12 (2): 458-463.
6. Giacomo Del Corso, Alessandro Villa. AchilleTarsitano, Anita Gohel. Current trends in Oral Cancer: A Review. Cancer Cell and Microenvironment. 2016; 3: 1-11.
7. Ravi Mehrotra, Yadav S. Oral Squamous Cell Carcinoma: Etiology, Pathologenesis and Prognostic Value of genomic alterations. Indian Journal of Cancer. 2006. 43 (2): 60-66.
8. ShilpasreeA S, Kiran Kumar, Itagappa M, Gayathri Ramesh. Study of oxidative stress and Antioxidant status in oral cancer patients. IJOMP. 2013; 4 (2): 02-06.
9. NuriaMut-Salud, pabo Juan Alvarez, Jose Manuel Garrido, Esther carras Co, Antonia Aranega, Fernando Rodriguez- Serrano. Antioxidant intake and Antitumour therapy: Toward Nutritional Recommendations for optimal Results. Oxidative Medicine and Cellular Liongevity. 2016. Article ID 6719534, 19 pages.
10. Elisa Couto Gomes, AlbenaNunes Silva, Marta Rubino De Oliveira, . Oxidants, Antioxidants and the Beneficial Roles of exercise- Induced Production of Reactive Species. Oxidative Medicine and Cellular Liongevity. 2012; Article ID 756132. 12 pages.
11. Rizzo A M, et al. Endogenous antioxidants and radical scavengers. AdvExp Med Biol. 2010; 698: 52-67.
12. Tomas AlegandroFregoso Aguilar, Brenda Caroline Hernandez Navarro, Jorge Alberto Mendoza Perez. Endogenous Antioxidants: A Review of their role in Oxidative stress. A Master Regulator of Oxidative stress.-The Transcription Factor Nrf2. 2016; Chapter 1: 3-19.
13. LawelA O, Kolude B, adeyemi B F. Serum uric acid levels in the oral cancer patients seen at Tertiary institutions in Nigeria. Ann Ib Postgrad Med. 2012. 10 (1): 9-12.
14. Thelma L Skare et al. Uric acid and Tissue repair. ABCD Arq Bras Cir Dig. 2015; 28 (4): 290-292.
15. Settle T, Hillarklandorf. The role of Uric acid as an Antioxidant in Neurogenerative Disease pathogenesis. Brain DisordTher. 2014; 3(3): 129.
16. SyedaArshiyaAra, Sajna Ashraf, Bhagyashree M Patil. Evaluation of of serum uric acid levels in patients with oral Squamous Cell Carcinoma. Indian j Den Res. 2016; 27 (2): 178-183.
17. Martelanc M, Zinberna L, Passsamonti S, Franko M. Direct determination of free bilirubin in serum at subnanomolar levels. AnalyticaChimicaActa. 2014; 809: 174-182.
18. Lovro Ziberna, Mitja Martelanc, MladenFranko Sabina Passamonti. Bilirubin ia an Endogenous antioxidant in human vascular Endothelial cells. Scientific reports 6. 2016; Article No 29240.
19. YingruLio, Ping Li, Jie Lu, Weixiong, Joel Oger, Wolfram Tetzlaft, Max Cynader. Bilirubin possesses powerful Immuno modulatory Activity and suppresses Experimental Autoimmune Encephalomyelitis. The Journal of Immunology. 2008; 181: 1887-1897.
20. William Otero Regino, Hector Velasco, Hector Sandovel. The protective role of bilirubin in human beings. Rev col Gastroenterol. 2009; 24 (3): 287-294.
21. Mendez et al. clinical implications of Bilirubin- Associated Neuroprotection and Neurotoxicity. Int J ClinAnesthesiol. 2013; 1 (2): 1013.
22. JaimaKapitulnik. Bilirubin: an Endogenous product of Heme degradation with both cytotoxic and cytoprotective properties. Molecular Pharmacology. 2004; 66: 773-779.
Received on 10.04.2018 Modified on 11.06.2018
Accepted on 02.07.2018 © RJPT All right reserved
Research J. Pharm. and Tech 2018; 11(10): 4362-4364.
DOI: 10.5958/0974-360X.2018.00798.9