Glutathione cycle in stable chronic obstructive pulmonary disease

Abstract

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.

Andrographolide protects against cigarette smoke‐induced oxidative lung injury via augmentation of Nrf2 activity

“…Alternatively, andrographolide has also demonstrated potent antioxidant activity by enhancing both GPx and GR activities in lung tissues from cigarette smoke‐exposed mice. GPx and GR play a critical role in generating GSH, an endogenous non‐protein thiol with potent free radical scavenging capacity (Biljak et al ., ; Cantin, ; Gould et al ., ).…”

“…GCL is the rate‐limiting enzyme in the GSH biosynthesis pathway. This enzyme is a heterodimer comprising of the catalytic subunit GCLC and the regulatory subunit GCLM (Biljak et al ., ; Gould et al ., ). Overexpression of GCL in human granulosa tumour cells has been shown to increase total GSH levels and protect against H 2 O 2 ‐induced cell death (Cortes‐Wanstreet et al ., ).…”

Neutrophils and emerging targets for treatment in chronic obstructive pulmonary disease

“…There is evidence that the increase of ROS in COPD is further enhanced by a dysfunction of some of the protective mechanisms for oxidative stress, such as the glutathione cycle [107]. Current studies are trying to investigate if additional antioxidants, either via medication or via changes in the diet are able to delay the progression of COPD, as reviewed by Biswas et al and Barnes (TABLE 2) [21,108,109].…”

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

“…This program enhances the capacity of protein folding, attenuates the rate of de novo protein synthesis and increases the ability to degrade proteins localized in the ER. If homeostasis is not restored, a prolonged ER stress and the use of UPR entirely overtake the mechanisms of cellular protection, ultimately inducing apoptosis .…”