IMPROVEMENT IN REDOX HOMEOSTASIS AFTER CYTOREDUCTIVE SURGERY IN COLORECTAL ADENOCARCINOMA

colorectal cancer (CRC) as one the most common cancer type is associated with oxidative stress. Surgery is the only curative modality for early-stage CRC. The aim of this study was to evaluate the oxidative damage biomarkers as well as enzymatic and nonenzymatic antioxidants in patients with CRC before and after tumor resection in healthy controls. 60 patients with stage I/II colorectaL adenocarcinoma and 43 healthy controls were recruited in this study. We measured plasma levels of oxidative damage biomarkers, including advanced oxidation protein products (AOPP), advanced glycation end products (AGEs), malondialdehyde (MDA), and oxized low-density lipoprotein (ox-LDL) at baseline and after tumor removal. We also evaluated the plasma activuty of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) as enzymatic antioxidants and the ferric reducing antioxidants power (FRAP) assay for nonenzymatic antioxidant capacity. Patients with CRC had significantly higher AGE, AOPP, MDA, and ox-LDL and also FRAP levels and higher SOD and GPx and lower CAT activity levels compared to healthy controls (p<0,05). We did not observe any statistically significant correlation between redox biomarkers and the size and stage of tumor. AGEs (72,49 +/- 7.7 vs. 67.93 +/- 8.8, p< 0,001), AOPP (137.64 +/- 21.9 vs. 119.08 +/- 33.1 p<0,001), MDA (3.56 +/- 0.30 vs. 3.05 +/- 0.33 p< 0,001), and ox-LDL (19.78 +/- 0.97 vs. 16.94 +/- 1.02, p< 0,001) concentrations reduced significantly after tumor removal. The largest effect sizes were found in ox-LDL (d = - 2.853, 95% CI 2.50 - 3.19) and MDA (d = - 0.43 - 0.57). Serum FRAP lelvels (1097.5 +/-156.7 vs. 1239.3 +/- 290, p< 0,001) and CAT (2.34 +/- 0.34 vs. 2.63 +/- 0.38, p< 0,001), GPx (102.37 +/- 6.58 vs. 108.03 +/- 6.95, p< 0,001), and SOD (5.13 +/- 0.39 vs. 5.53 +/- 0,31 p< 0,001) activity levels increased significantly after surgery. The largest effect sizes among antioxidants were seen in SOD (d = 1.135, 95% CI 0.46 - 0.34) and GPx (d = 0.836, 95% CI 0.35 - 0.23>). This study indicated that patients with colorectal cancer high higher levels of oxidative stress and antioxidants activity compared to healthy controls. After surgical resection of tumor, we observed a substantial improvement in redox homeostasis

Effect of chemical chaperones on glucose-induced lysozyme modifications

Nonenzymatic glycation of biomacromolecules occurs due to the diabetes mellitus and ageing. A number of small molecules, known as chemical chaperones, stabilize protein conformation against thermal and chemically induced denaturation. These compounds are including: polyamines (e.g. spermine and spermidine), amino acids (e.g. lysine) and polyols (e.g. glycerol). In this study the effect of spermidine (Spd), spermine (Spm), and glycerol on glycation, structure and function of lysozyme (LZ), as an extra-cellular protein, by different techniques is investigated. LZ is incubated with or without glucose (50 or 100 mM) in the absence or presence of Spd/Spm/glycerol at 37 °C up to 16 weeks. All the observed changes of glycated-LZ in comparison with the native protein, including: increased fluorescence emission, alteration in the secondary and tertiary structure, and reduced electrophoretic mobility- indicate its structural changes that are accompanied with its reduced activity. Glucose in the presence or absence of Spd induces the protein dimerization, but glucose plus Spm induces its trimmerization. In contrast, glycerol inhibits the LZ glycation and prevents the large changes on its structure and function. Glucose binds lysine residues, decreases the protein positive charges and induces some alterations in its structure and activity. Polyamines also directly bind to LZ, increase its positive charges and hence induce more glycation; more conformational changes, oligomerization and its inactivation in the presence of glucose, but glycerol affect the protein environment and preserve protein from these harmful effects. © 2011 Springer Science+Business Media, LLC