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Antioxidant Barrier, Redox Status, and Oxidative Damage to Biomolecules in Patients with Colorectal Cancer. Can Malondialdehyde and Catalase Be Markers of Colorectal Cancer Advancement?

ABSTRACT: This study is the first to assess the diagnostic utility of redox biomarkers in patients with colorectal cancer (CRC). Antioxidant barrier (Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), uric acid (UA), reduced glutathione (GSH)), redox status (total antioxidant (TAC)/oxidant status (TOS), ferric reducing ability (FRAP)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), malondialdehyde (MDA)) were measured in serum/plasma samples of 50 CRC patients. The activity of SOD was significantly higher whereas the activity of CAT, GPx and GR was considerably lower in CRC patients compared to the control group (p < 0.0001). Levels of UA, TOS, and OSI and concentrations of AGE, AOPP, and MDA were significantly higher, and the levels of GSH, TAC, and FRAP were considerably lower in CRC patients compared to the healthy controls (p < 0.0001). AUC for CAT with respect to presence of lymph node metastasis was 0.7450 (p = 0.0036), whereas AUC for MDA according to the depth of tumour invasion was 0.7457 (p = 0.0118). CRC is associated with enzymatic/non-enzymatic redox imbalance as well as increased oxidative damage to proteins and lipids. Redox biomarkers can be potential diagnostic indicators of CRC advancement.

SUBMITTER: Zinczuk J

PROVIDER: S-EPMC6843197 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Antioxidant Barrier, Redox Status, and Oxidative Damage to Biomolecules in Patients with Colorectal Cancer. Can Malondialdehyde and Catalase Be Markers of Colorectal Cancer Advancement?

Zińczuk Justyna J Maciejczyk Mateusz M Zaręba Konrad K Romaniuk Wioletta W Markowski Adam A Kędra Bogusław B Zalewska Anna A Pryczynicz Anna A Matowicka-Karna Joanna J Guzińska-Ustymowicz Katarzyna K

Biomolecules 20191022 10

This study is the first to assess the diagnostic utility of redox biomarkers in patients with colorectal cancer (CRC). Antioxidant barrier (Cu,Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), uric acid (UA), reduced glutathione (GSH)), redox status (total antioxidant (TAC)/oxidant status (TOS), ferric reducing ability (FRAP)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), m ...[more]

PMID: 31652642

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Project description:Despite the proven role of oxidative stress in numerous systemic diseases and in the process of aging, little is still known about the salivary redox balance of healthy children, adults, and the elderly. Our study was the first to assess the antioxidant barrier, redox status, and oxidative damage in nonstimulated (NWS) and stimulated (SWS) saliva as well as blood samples of healthy individuals at different ages. We divided 90 generally healthy people into three equally numbered groups based on age: 2-14 (children and adolescents), 25-45 (adults), and 65-85 (elderly people). Antioxidant enzymes (salivary peroxidase (Px), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase-1 (SOD)), nonenzymatic antioxidants (reduced glutathione (GSH) and uric acid (UA)), redox status (total antioxidant capacity (TAC), total oxidant status (TOS), and oxidative stress index (OSI)), and oxidative damage products (advanced glycation end products (AGE), advanced oxidation protein products (AOPP), and malondialdehyde (MDA)) were evaluated in NWS and SWS as well as in erythrocyte/plasma samples. We demonstrated that salivary and blood antioxidant defense is most effective in people aged 25-45. In the elderly, we observed a progressive decrease in the efficiency of central antioxidant systems (↓GPx, ↓SOD, ↓GSH, and ↓TAC in erythrocytes and plasma vs. adults) as well as in NWS (↓Px, ↓UA, and ↓TAC vs. adults) and SWS (↓TAC vs. adults). Both local and systemic antioxidant systems were less efficient in children and adolescents than in the group of middle-aged people, which indicates age-related immaturity of antioxidant mechanisms. Oxidative damage to proteins (↑AGE, ↑AOPP) and lipids (↑MDA) was significantly higher in saliva and plasma of elderly people in comparison with adults and children/adolescents. Of all the evaluated biomarkers, only salivary oxidative damage products generally reflected their content in blood plasma. The level of salivary redox biomarkers did not vary based on gender.

Project description:Ataxia-telangiectasia (AT) and Nijmegen breakage syndrome (NBS) belong to a group of primary immunodeficiency diseases (PI) characterized by premature aging, cerebral degeneration, immunoglobulin deficiency and higher cancer susceptibility. Despite the fact that oxidative stress has been demonstrated in vitro and in animal models of AT and NBS, the involvement of redox homeostasis disorders is still unclear in the in vivo phenotype of AT and NBS patients. Our study is the first to compare both enzymatic and non-enzymatic antioxidants as well as oxidative damage between AT and NBS subjects. Twenty two Caucasian children with AT and twelve patients with NBS were studied. Enzymatic and non-enzymatic antioxidants - glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase-1 (SOD) and uric acid (UA); redox status-total antioxidant capacity (TAC) and ferric reducing ability of plasma (FRAP); and oxidative damage products-8-hydroxy-2'-deoxyguanosine (8-OHdG), advanced glycation end products (AGE), advanced oxidation protein products (AOPP), 4-hydroxynonenal (4-HNE) protein adducts, and 8-isoprostanes (8-isop) were evaluated in serum or plasma samples. We showed that CAT, SOD and UA were significantly increased, while TAC and FRAP levels were statistically lower in the plasma of AT patients compared to controls. In NBS patients, only CAT activity was significantly elevated, while TAC was significantly decreased as compared to healthy children. We also showed higher oxidative damage to DNA (↑8-OHdG), proteins (↑AGE, ↑AOPP), and lipids (↑4-HNE, ↑8-isop) in both AT and NBS patients. Interestingly, we did not demonstrate any significant differences in the antioxidant defense and oxidative damage between AT and NBS patients. However, in AT children, we showed a positive correlation between 8-OHdG and the α-fetoprotein level as well as a negative correlation between 8-OHdG and IgA. In NBS, AGE was positively correlated with IgM and negatively with the IgG level. Summarizing, we demonstrated an imbalance in cellular redox homeostasis and higher oxidative damage in AT and NBS patients. Despite an increase in the activity/concentration of some antioxidants, the total antioxidant capacity is overwhelmed in children with AT and NBS and predisposes them to more considerable oxidative damage. Oxidative stress may play a major role in AT and NBS phenotype.

Dataset Information

Antioxidant Barrier, Redox Status, and Oxidative Damage to Biomolecules in Patients with Colorectal Cancer. Can Malondialdehyde and Catalase Be Markers of Colorectal Cancer Advancement?

Publications

Antioxidant Barrier, Redox Status, and Oxidative Damage to Biomolecules in Patients with Colorectal Cancer. Can Malondialdehyde and Catalase Be Markers of Colorectal Cancer Advancement?

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