Gamma-glutamyltransferase and C-reactive protein in stable chronic obstructive pulmonary disease.

Systemic inflammation and oxidative stress are the most important features of chronic obstructive pulmonary disease (COPD). The presence of oxidative stress in the airways of smokers, the largest population of COPD patients, is a consequence of direct inhalation of cigarette smoke and increased inflammation-related production of reactive oxygen species. On the other hand, oxidative stress appears to be the key component of many processes associated with chronic inflammation. We intend to examine whether serum C-reactive protein (CRP) concentration and gamma-glutamyltransferase (GGT) activity might be used as auxiliary markers in monitoring level of oxidative stress and inflammation in clinically stable COPD. We also investigated influence of cigarette smoking on these two systemic parameters. Catalytic activity of GGT and concentration of CRP were determined in sera of COPD patients (N = 109) and in healthy controls (N = 51) by using standard spectrophotometric method and immunoturbidimetric method, respectively. Concentration of CRP and activity of GGT were increased in COPD patients, as compared to healthy controls (p < 0.05). We found a significant positive correlation between those two parameters in COPD patients (r = 0.202, p = 0.0371). Our results showed no difference in GGT activity (p = 0.606) or CRP concentration (p = 0.573) between groups of patients when subdivided according to the severity of the disease. Smoking did not have a significant impact on CRP and GGT values in COPD patients and healthy controls. We showed an increase of serum CRP and GGT values in COPD patients, and we suggest that serum GGT activity might also represent an inflammation/oxidative stress marker. It seems that COPD patients present higher serum CRP and GGT values than healthy subjects independently from their smoking habits.

Carboplatin resistant human laryngeal carcinoma cells are cross resistant to curcumin due to reduced curcumin accumulation.

Curcumin is a natural compound that exhibits a wide range of beneficial effects, among them the anti-tumor activity. Recently it was shown that curcumin may be efficient against drug resistant tumor cells. The goal of our investigation was to examine if human laryngeal carcinoma cells resistant to carboplatin display sensitivity to curcumin, as compared to parental cells, and if this sensitivity is altered, to determine the molecular mechanisms that are responsible for it. We found that carboplatin resistant 7T cells were also cross resistant to curcumin. After the treatment with equimolar concentration of curcumin, 7T cells exhibited lower intracellular accumulation of curcumin which coincided with reduced formation of reactive oxygen species (ROS), diminished lipid and DNA damage followed by reduced induction of apoptosis and expression of heat shock protein 70 (Hsp70), as compared to parental HEp-2 cells. However, after the treatment with equitoxic concentration of curcumin, intracellular accumulation and all the explored downstream effects were similar in both cell lines suggesting that resistance of 7T cells to curcumin was based on its reduced intracellular accumulation. Since curcumin accumulates mostly in the membranes, we explored the fatty acid composition of both cell lines, but we did not find any difference between them.

Glutathione cycle in stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation and oxidant/antioxidant imbalance. Glutathione is the most abundant cellular low-molecular weight thiol and the glutathione redox cycle is the fundamental component of the cellular antioxidant defence system. Concentration of total glutathione and catalytic activities of glutathione peroxidase and glutathione reductase were determined in peripheral blood of patients (n = 109) and healthy subjects (n = 51). Concentration of total glutathione in patients was not changed in comparison to healthy controls. However, we found statistically significant difference between patients with moderate and severe disease stages. Glutathione reductase activity was increased, while glutathione proxidase activity was decreased in the patients with COPD, when compared to healthy controls. We found no significant difference in glutathione peroxidase and glutathione reductase activities between stages. Patients who smoked had lower concentration of total glutathione compared with former smokers and never-smoking patients. Lung function parameters were inversely associated with glutathione level. Evidence is presented for differential modulation of glutathione peroxidase and glutathione reductase activities in peripheral blood of patients with stable COPD. We suppose that in addition to glutathione biosynthesis, glutathione reductase-dependent regulation of the glutathione redox state is vital for protection against oxidative stress.

Lithium effect on glutamate induced damage in glioblastoma cells.

Lithium, besides mood stabilization, might be involved in neuroprotection. Previously we have found that the treatment with lithium increased the levels of p21(WAF/Cip1 and survivin in human glioblastoma A1235 cells. The aim of the present study was to examine the cytotoxic effect of glutamate on these cells, and to determine whether lithium can protect A1235 cells against toxic effects of glutamate. Cytotoxicity of glutamate was examined by spectrophotometric MTT assay, while the expression of apoptosis related genes was examined by Western blot method. Glutamate was excessively cytotoxic for A1235 cells only in concentrations higher than 100 mM. It did not induce apoptosis, but rather suppressed survivin expression and increased the level of p21(WAf/Cip1). Pretreatment with lithium (2 mM) partially reverted change in survivin expression induced by glutamate, suggesting that lithium may have beneficial effect on glutamate induced cell damage in glioblastoma cells.