Myeloperoxidase enzyme levels and oxidative stress in bipolar disorders

Oxidative stress and generalized inflammatory state are features of bipolar disorders (BD). The objective of this study was to compare the levels of products of inflammatory reaction and oxidative stress markers in patients with bipolar disorders and attention deficit/hyperactivity disorder (ADHD) and to determine the relationship between oxidative stress and inflammation in bipolar disorders. ADHD+BD (n = 30) and BD (n = 30) and healthy controls (n = 30) were enrolled. A clinical evaluation andmeasurements of malondialdehyde (MDA), high sensitive C reactive protein (hsCRP) and myeloperoxidase (MPO) were performed. Patients with BD+ADHD comorbidity had significantly higher mean MPO levels than BD. Patients with BD had significantly higher mean hsCRP levels than healthy controls. However, there was no significant difference in mean serum hsCRP levels between patients with BD+ADHD and healthy controls. Patients with BD and BD+ADHD had significantly higher mean MDA levels than healthy controls. Our data showed that there is an increased susceptibility to oxidative stress which is strongly related to the serum levels of MDA produced in the serum. hsCRP levels were higher in BD patients than in BD+ADHD and this is suggestive of a higher degree of inflammatory activity in BD patients. ADHD+BD comorbidity seems to augment oxidative stress which is expressed as increased MPO level in the present study. Further large scale studies are needed to extend ourresults

Menopausal Status Modifies Breast Cancer Risk Associated with the Myeloperoxidase (MPO) G463A Polymorphism in Caucasian Women: A Meta-Analysis

BACKGROUND: Breast cancer susceptibility may be modulated partly through polymorphisms in oxidative enzymes, one of which is myeloperoxidase (MPO). Association of the low transcription activity variant allele A in the G463A polymorphism has been investigated for its association with breast cancer risk, considering the modifying effects of menopausal status and antioxidant intake levels of cases and controls. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a more precise estimate of association using the odds ratio (OR), we performed a meta-analysis of 2,975 cases and 3,427 controls from three published articles of Caucasian populations living in the United States. Heterogeneity among studies was tested and sensitivity analysis was applied. The lower transcriptional activity AA genotype of MPO in the pre-menopausal population showed significantly reduced risk (OR 0.56-0.57, p = 0.03) in contrast to their post-menopausal counterparts which showed non-significant increased risk (OR 1.14; p = 0.34-0.36). High intake of antioxidants (OR 0.67-0.86, p = 0.04-0.05) and carotenoids (OR 0.68-0.86, p = 0.03-0.05) conferred significant protection in the women. Stratified by menopausal status, this effect was observed in pre-menopausal women especially those whose antioxidant intake was high (OR 0.42-0.69, p = 0.04). In post-menopausal women, effect of low intake elicited susceptibility (OR 1.19-1.67, p = 0.07-0.17) to breast cancer. CONCLUSIONS/SIGNIFICANCE: Based on a homogeneous Caucasian population, the MPO G463A polymorphism places post-menopausal women at risk for breast cancer, where this effect is modified by diet

Levels of plasma vitamin E, vitamin C, TBARS, and cholesterol in male patients with colorectal tumors

Vitamin E and vitamin C are involved in the defense of the body against free radical and reactive oxygen molecule induced damage. The best characterized biological damage caused by radicals is known as lipid peroxidation. Free radical formation is known to play a major role in the development of cancer. In this study, we measured plasma levels of thiobarbituric acid reactive substances (TBARS) as a marker of lipid peroxidation, cholesterol, and vitamins E and C as antioxidants in male patients with colorectal tumors (n = 20, 54.5 +/- 8.3 years). The patients had significantly higher plasma TBARS levels than age-matched healthy subjects (p < 0.001). Plasma vitamin C levels were significantly lower in the patients compared to the healthy subjects (p < 0.001). On the other hand, plasma vitamin E levels in the patients were similar to those of healthy subjects. Plasma cholesterol levels were also found to be significantly elevated in patients with colorectal tumors (p < 0.00 1). Our results suggest that there is an imbalance between oxidant and antioxidant status in tumor genesis

Glutathione and glutathione-related enzymes in colorectal cancer patients

In recent years much attention has been focused on the role of glutathione (GSH) and GSH-related enzymes such as glutathione peroxidase (GSH Px), glutathione reductase (GSH Red), and glutathione S-transferase (GST) in the inhibition of free radical-inducec carcinogenesis. In this study, erythrocyte GSH levels and activities of GSH Px, GSH Red, and GST were determined in patients with colorectal tumors (n = 20, mean age 54.5 +/- 8.3 yr). Erythrocyte GSH Red and GST activities were significantly higher in patients with colorectal tumors. Erythrocyte GSH levels and GSH Px activities were found to be significantly decreased in the patients. When the patients were classified based on their clinical grading (Dukes classifications), there was no significant difference in studied parameters between Dukes B and Dukes C. Our results suggest that oxidative stress may play an important role in colorectal tumorigenesis and that these events have no effect on the clinical grading of the colorectal tumor

DNA damage, DNA susceptibility to oxidation and glutathione level in women with polycystic ovary syndrome

Recent studies have addressed the possibility of an association between polycystic ovaries and ovarian cancer. DNA damage is the first step of the carcinogenesis, and susceptibility to cancer, in general, is characterized by high DNA damage. Free radical-mediated DNA damage and impaired antioxidant defence have been implicated as contributory factors for the development of cancer. This study evaluates DNA damage (strand breakage, base oxidation, formamidopyrimidine DNA glycosylase (Fpg) sensitive sites), H2O2-induced DNA damage, a marker of DNA susceptibility to oxidation and glutathione (GSH) level, a powerful antioxidant, in women with polycystic ovary syndrome (PCOS). Women with PCOS showed a significant decrease in GSH level, a significant increase in DNA strand breakage and H2O2-induced DNA damage. Although Fpg-sensitive sites were higher in the PCOS group compared to the control group, the difference did not reach a statistically significant level. Significant correlations were found between free testosterone and DNA strand breakage (r = 0.46, p < 0.01) and free testosterone and H2O2-induced DNA damage (r = 0.41, p < 0.05). The data indicate that DNA damage and susceptibility of DNA to oxidative stress are increased in women with PCOS and may explain the association between PCOS and ovarian cancer

Methylguanine DNA methyl transferase activities, glutathione S transferase and nitric oxide in bladder cancer patients

Tumor formation is a multistep process that can be divided in to the stages of tumor initiation, promotion, and progression. DNA repair protein; MGMT is a key suicide enzyme that repairs the mispairing base methylguanine, which is induced in DNA as a minor lesion. The glutathione S transferases (GSTs) are a family of enzymes that are important to protect against alkylating agents. Nitric oxide, contributes to the regulation of tumor angiogenesis. A substantial body of experimental evidence supports the hypothesis that tumor angiogenesis is fundamental for the growth and metastasis of solid tumors. We measured the activities of GST, MGMT, and levels of NO 3 - /NO 2 - in the leukocytes from patients with bladder carcinoma and healthy controls and activities of MGMT in the tissue from patients with bladder carcinoma and adjacent normal tissue in bladder. Both GST and tissue MGMT activites were significantly increased in the patient group. There was no significant difference between controls and patients for MGMT activity in peripheral blood leukocytes (PBL). Nitrate/nitrite levels in PBL, there was no significant difference between controls and patients. Nitrate/nitrite levels were increased in G2-G3 tumors. In conclusion, we determined high concentrations of nitrite in leukocytes are suspected alkylation damage by induction nitrosamine. Increased DNA alkylation damage may lead the stimulation of MGMT and GST

Glutathione peroxidase 1 (GPX1) genetic polymorphism, erythrocyte GPX activity, and prostate cancer risk

Glutathione peroxidase 1 (GPX1) is a ubiquitously expressed selenium-dependent enzyme that protects cells against oxidative damage by reducing hydrogen peroxide and a wide range of organic peroxides. Some epidemiological studies have correlated low GPX activity or particular GPX1polymorphisms with enhanced risk of cancer, although these correlations have not been consistently observed in all populations. Therefore, we conducted the present study to evaluate the possible association of GPX1 Pro198Leu polymorphism and erythrocyte GPX activity with the risk of developing prostate cancer and to clarify whether erythrocyte GPX activity levels were correlated with the GPX1 Pro198Leu genotype in the Macedonian population. The GPX1 Pro198Leu genotype was determined in 82 prostate cancer cases and 123 control individuals. We found an overall protective effect of the variant Leu allele of the GPX1 polymorphism on the prostate cancer risk. Heterozygous carriers of the variant Leu allele had a significantly lower risk of prostate cancer compared with homozygous wild-type individuals (OR, 0.38; 95% CI, 0.20–0.75; P = 0.004). Erythrocyte GPX activity was analyzed in 73 cases and 91 controls. The erythrocyte GPX activity in the cancer group was lower than in the healthy controls. Additionally, we compared the erythrocyte GPX activity in the control group of 90 subjects and found no significant differences by genotype. These findings suggest that individual susceptibility of prostate cancer may be modulated by GPX1 polymorphism and that the combination of genetic factors involved in oxidative response with environmental carcinogens may play an important role in prostate carcinogenesis