Role of diagnostic factors associated with antioxidative status and expression of matrix metalloproteinases (MMPs) in patients with cancer therapy induced ocular disorders

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.

miR‐134 inhibits osteosarcoma cell invasion and metastasis through targeting MMP1 and MMP3 in vitro and in vivo

“…This finding is consistent with previously published studies reporting that diallyl disulfide inhibited osteosarcoma cell invasion by the upregulation of miR‐134 and showing that miR‐134 reduced nonsmall cell carcinoma cell migration and invasiveness through inhibition of MMP7 and MMP9. Furthermore, the targeting of MMPs has been demonstrated to benefit cancer patients clinically . miR‐134 might serve as a broad target to reduce the function of multiple MMPs.…”

Effect of vincristine on intraocular pressure and tear fluid oxidative stress biomarkers in canine transmissible venereal tumor

“…Many chemotherapy such as anthracyclines, bleomycin, vincristine, cyclophosphamide exert their effects partly through the oxidative pathway, and ocular toxicity from these medications may manifest as changes in the ocular surface and tear film. 40,41 A study on lung cancer patients, who underwent combined chemotherapy with vincristine, showed a significant increase in oxidative stress levels, lipid peroxidation, and a decrease in antioxidant levels. 42 The results of this study showed that the oxidative stress factors present in the tear samples changed after the administration of vincristine compared to before the administration of this drug in such a way that the total oxidative status, malondialdehyde, and oxidative stress index before and after chemotherapy and also during the weeks, shows an increasing trend and the total antioxidant capacity decreases before and after chemotherapy as well as during the week.…”

“…45 A second hypothesis is that increased levels of pro-inflammatory and inflammatory interleukins, lower levels of antioxidant enzymes and nonenzymatic small molecules, and oxidative stress such as NO, MDA, and OSI may contribute to the pathogenesis of systemic chemotherapy-related ocular complications such as cataracts, glaucoma, blepharitis, retinitis pigmentosa, macular degeneration, pterygium, and retinal degeneration. 41 Examining eye disorders and side effects following chemotherapy is one of the most important factors evaluated by physicians and veterinarians. IOP is one of the easiest ways to evaluate eye changes, and besides that, checking tear parameters can evaluate the health status or eye changes over time.…”

Dynamic Thiol Disulphide Homeostasis in Patients with Surfer’s Eye: A Case-Control Study

“…In another study, Rasool M. Et al. [25] pointed to a higher level of oxidative stress and in ammatory clinical parameters such as nitric oxide, malondialdehyde, tumor necrosis factor-α and matrix metalloproteinases-9 and a lower level of non-enzymatic small molecules and antioxidant enzymes in cancer patients following systemic chemotherapy. The authors of this study argued that these parameters could also take part in the pathogenesis of ocular complications related to systemic chemotherapy such as retinal degeneration, glaucoma, cataract, blepharitis, pterygium, macular degeneration and retinitis pigmentosa.…”