Oxidative stress in non-small cell lung cancer: role of nicotinamide adenine dinucleotide phosphate oxidase and glutathione.

BACKGROUND: Cigarette smoke is strongly associated with NSCLC, but the carcinogenesis of NSCLC is poorly understood. METHODS: To discover the role of oxidative stress and anti-oxidative defense in NSCLC, we measured NADPH oxidase (NOX) activity, myeloperoxidase activity, 8-OHdG, and glutathione content from lung specimens. These came from 32 patients: 22 NSCLC patients and ten controls without cancer. RESULTS: In NSCLC patients, NOX activity was significantly higher both in the malignant (p = 0.001) and non-malignant (p = 0.044) samples from NSCLC patients, than in the control specimens. Myeloperoxidase activity was lower (p = 0.001) and glutathione content (p = 0.009) higher in malignant tissue. No significant difference was observable in 8-OHdG content between patient groups. CONCLUSIONS: Increase in NOX activity in the malignant tissues was independent of smoking history and myeloperoxidase activity, suggesting its independent role in NSCLC pathogenesis.

Gastroesophageal reflux patients' defective antioxidative capacity in the proximal esophageal mucosa before antireflux surgery and also after 4-year follow-up.

BACKGROUND: Oxidative stress has a role in the pathogenesis of gastroesophageal reflux disease (GERD). AIM: To investigate the redox balance in proximal esophagus before and 6 and 48 months after antireflux surgery. METHODS: In 20 GERD patients and 9 controls oxidative stress by myeloperoxidase activity (MPO activity) and antioxidative capacity of esophageal mucosa by superoxide dismutase activity (SOD), and glutathione content (GSH) was measured from proximal esophageal samples. RESULTS: In proximal esophagus of GERD patients compared to controls', antioxidative capacity appearing as GSH level was significantly decreased (P < 0.001) at all time points and as SOD levels preoperatively (P < 0.001) and 4 years postoperatively (P = 0.01). MPO activity of patients was significantly lower than controls' preoperatively, and 6 months and 4 years postoperatively (P < 0.05). MPO activity remained lower than that of the distal esophagus at 6 months and 4 years (P < 0.01 for both). CONCLUSIONS: In GERD patients, proximal esophageal mucosal antioxidative defense is defective before and after antireflux surgery. Antireflux surgery seems not to change the level of oxidative stress in proximal esophagus, suggesting that defective mucosal antioxidative capacity plays a role in development of oxidative damage to the esophageal mucosa in GERD.

The impact of antireflux surgery on oxidative stress of esophageal mucosa caused by gastroesophageal reflux disease: 4-yr follow-up study.

BACKGROUND AND AIM: Oxidative stress to esophageal mucosa plays a key role in the pathogenesis of gastroesophageal reflux disease (GERD), Barrett's esophagus, and adenocarcinoma. We investigated whether successful antireflux surgery eliminates oxidative stress. METHODS: Oxidative stress of esophageal mucosa was measured in 20 GERD patients, before antireflux surgery and 6 and 48 months after it, and compared with normal controls' mucosa (N = 9). Preoperatively, 12 of the 20 had erosive esophagitis or Barrett's metaplasia. Postoperatively, healing of GERD was verified with endoscopy and 24-h pH monitoring. We measured oxidative stress by myeloperoxidase activity (MPA), superoxide dismutase activity, and glutathione content (GSH) in distal esophagus samples from endoscopy. RESULTS: No patient had reflux symptoms after surgery, and pH measurements had normalized. MPA in the distal esophagus decreased (p < 0.05) after successful antireflux surgery, but remained higher than that of controls both 6 months and 4 yr postoperatively (p < 0.05). At all time-points, MPA was higher in patients with preoperatively detected erosive reflux disease (ERD) as compared to non-erosive reflux disease (NERD) (p < 0.01, p < 0.05, and p < 0.05, respectively). GSH values decreased with time only in NERD. At all time-points, GSH levels in distal esophagus were lower than control levels. CONCLUSIONS: Antireflux surgery can heal macroscopic esophagitis but cannot fully reverse the oxidative stress (as reflected by MPA and GSH) upon the distal esophageal mucosa.

Antioxidant activity of knotwood extractives and phenolic compounds of selected tree species.

The antioxidant potency and the radical scavenging capacity of superoxide and peroxyl radicals were assessed for 13 hydrophilic knotwood extracts of commercially important wood species, or fractions thereof, as well as for five pure wood-derived lignans and the flavonoid taxifolin. The chemical composition of the knotwood extracts was determined by gas chromatography combined with mass spectrometry. Most of the investigated wood species were rich in hydrophilic extractives (10-20% of the dry wood) with one or a few compounds dominating in each extract. All extracts had a high antioxidative potency and/or radical scavenging capacity as compared to the well-known antioxidants Trolox and butylated hydroxyanisole. The pure wood-derived lignans and taxifolin also had a high antioxidative potency and/or radical scavenging capacity. However, the antioxidant potency and/or radical scavenging capacity of several of the hydrophilic knotwood extracts were higher than that of the dominating compounds in pure form.

Increased DNA adducts in Barrett's esophagus and reflux-related esophageal malignancies.

BACKGROUND: DNA adduct formation can initiate carcinogenic processes. AIM: To examine the pre-malignant condition of Barrett's esophagus by measuring the DNA adducts. METHODS: DNA adducts were measured in the proximal and distal esophagus of patients with Barrett's esophagus (n = 9), patients with adenocarcinoma in the distal esophagus/esophagogastric junction (n = 28), and in control group of patients (n = 8) using the 32-P-postlabeling method. The average levels of DNA adducts are expressed as mean adducts/10(9) nucleotides + standard error of the mean. RESULTS. The average DNA adduct levels in the distal esophagus were significantly higher in both the Barrett's esophagus (24.5 +/- 7.9) and the adenocarcinoma (12.0 + 3.0) than in the control patients (0.1 +/- 0.08), P < 0.001. In the proximal esophagus, the DNA adduct levels were approximately equal in the Barrett's esophagus (7.0 +/- 1.0) and in the adenocarcinoma group (6.4 +/- 0.65). However, the levels in the proximal esophagus in both groups were significantly higher than in the control group (2.1 +/- 0.67), P < 0.05. CONCLUSIONS: Patients with Barrett's esophagus and patients with esophageal/esophagogastric junction adenocarcinoma had significantly more DNA adducts than the control group. These results support the current concept of the carcinogenic potential of chronic gastroesophageal reflux, and the pre-malignant condition of Barrett's esophagus.