Antioxidant Defense Expressed as Glutathione Status and Keap1-Nrf2 System Action in Relation to Anthropometric Parameters and Body Composition in Young Women with Polycystic Ovary Syndrome

Abstract

Metabolic disorders present in women with polycystic ovary syndrome (PCOS) and the associated risk of obesity may result in increased oxidative stress and reproductive failure. Therefore, we evaluated the concentrations of reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione peroxidase (GPx), and reductase (GR), as well as nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associating protein1 (Keap1) in the serum of 56 women with PCOS divided according to the visceral to subcutaneous fat surface ratio (VAT/SAT) and waist-to-hip ratio (WHR) values. Antioxidant parameter levels were measured by competitive inhibition enzyme immunoassay technique. As the VAT/SAT ratio and WHR increased, we observed significantly higher concentrations of GSSG and Keap1 protein and a lower value of the GSSG/GSH ratio (R-index), which is considered an index of cellular redox (p < 0.05). Negative correlations were found between the R-index and body weight, BMI, WHR, subcutaneous and visceral fat surface and the VAT/SAT ratio, and total body fat; positive links were found with fat free mass and total body water. Opposite associations were noted between GSSG level and the aforementioned body composition parameters. Oxidative stress characterized by a depleted reduced-to-oxidized glutathione index is associated with anthropometric and body composition parameters in women with PCOS. In particular, abdominal obesity expressed by the VAT/SAT ratio and/or WHR seems to have a negative impact on glutathione status, which may lead to a disruption of many biological cell processes. The observed negative association of Keap1 with R-index suggests that the elevated oxidative changes dependent on the VAT/SAT ratio may lead to Nrf2 activation to promote antioxidant enzyme expression. Although the GSH/GSSG index as well as the VAT/SAT ratio appear to be good indicators of oxidative status, studies on a larger group of patients should continue to confirm these links among women with PCOS.

Keywords

• polycystic ovary syndrome
• glutathione
• glutathione peroxidase
• glutathione reductase
• obesity
• oxidative stress