Role of diagnostic factors associated with antioxidative status and expression of matrix metalloproteinases (MMPs) in patients with cancer therapy induced ocular disorders |
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Authors: | Mahmood Rasool Arif Malik Muhammad Abdul Basit Ashraf Mahwish Arooj Asia Kiran Sulayman Waquar Ujala Ayyaz Ayesha Zahid Ahmad Zaheer Abdul Jabbar Maryam Zain Amir Raza Asim Mehmood Tahira Batool Qaisrani Zeenat Mirza Mohammed Hussein Al-Qahtani Sajjad Karim Absarul Haque |
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Institution: | 1. Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, Saudi Arabia;2. Institute of Molecular Biology and Biotechnology, the University of Lahore, Lahore, Pakistan;3. University College of Medicine and Dentistry, the University of Lahore, Lahore, Pakistan;4. National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan;5. Department of Biotechnology, Mirpur University of Science and Technology (MUST), Mirpur (AJK), Pakistan;6. Microbiology and Molecular Genetics Department, The Women University, Multan, Pakistan;7. Department of Biosciences, COMSATS University, Sahiwal Campus, Sahiwal, Pakistan;8. Faculty of Agricultural Sciences, Ghazi University, Dear Ghazi Khan, Pakistan;9. King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia |
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Abstract: | BackgroundCancer patients when treated with different chemotherapeutic drugs often develop mild to severe sight threatening diseases during or after chemotherapy. The mechanism involved in the pathogenesis of ocular toxicities is poorly understood. Oxidative stress, inflammation and MMPs (angiogenic factor) are involved in the progression of chemotherapy related ocular disorders.Materials and methodsThe concentration of oxidative stress markers such as MDA, NO and levels of different antioxidant molecules such as SOD, CAT, GSH, GPx, GPr, VIT A, VIT E and VIT C present in the serum of chemotherapy treated patients (n?=?50) and in normal persons (n?=?20) were estimated by the direct spectrophotometric method while the concentration of TNF-α and MMP-9 activity were determined using human TNF-α and MMP-9 ELISA kits.ResultsThe concentration of SOD and CAT (0.356?±?0.05?μg/dl and 1.26?±?0.01?μmol/mol of protein) was significantly lower as compared to that (1.09?±?0.03?μg/dl and 3.99?±?0.04?μmol/mol of protein) in controls. The levels of GPx (0.06?±?0.01?mmol/dl) in the cancer patients were much lower than those in the controls (0.78?±?0.06?mmol/dl). Lower level of GSH (0.96?±?0.003?μg/dl) in serum of the diseased group was observed as compared to healthy group (7.26?±?1.40?μg/dl). The level of Vit A, Vit C and Vit E was lower in systemic circulation of cancer patients (109.99?±?6.35?μg/ml, 1.26?±?0.36?μg/ml and 1.29?±?0.191?μg/ml) as compared to control subjects (166.35?±?14.26?μg/ml, 3.25?±?0.099?μg/ml and 6.354?±?2.26?μg/ml) respectively. The concentration of nitric oxide was significantly higher in the cancer patients (45.26?±?6.35?ng/ml) than that in the normal subjects (16.35?±?3.26?ng/ml). The higher concentration of MDA (8.65?±?3.26?nmol/ml) was observed in the patients than normal ones (1.254?±?0.065?nmol/ml). The quantity of TNF-α was significantly higher in chemotherapy treated patients (32.68?±?4.33?pg/ml) as compared to the control group (20.979?±?1.98?pg/ml). Significantly higher concentration of MMP-9 (40.26?±?3.26?ng/ml) was observed in the cancer patients than the controls (7.256?±?1.95?ng/ml).ConclusionLower levels of antioxidant enzymes and non-enzymatic small molecules and higher levels of oxidative stress and inflammatory clinical parameters such as NO, MDA, TNF-α and MMP-9 may be involved in the pathogenesis of systemic chemotherapy related ocular complications such as cataract, glaucoma, blepharitis, retinitis pigmentosa, macular degeneration, pterygium and retinal degeneration. |
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Keywords: | NO nitric oxide MDA malondialdehyde TNF tumor necrosis factor IL interleukin MMPs matrix metalloproteinases HIV human immunodeficiency virus ROS reactive oxygen species Oxidative stress Cancer Chemotherapeutic drugs TNF-α MMPs Ocular complications |
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