Oxidative stress parameters of Gaucher disease type I patients

Abstract

Enzymatic deficiency in Gaucher disease (GD) patients may induce a cascade of events, culminating in secondary effects such as the production of reactive oxygen species (ROS). Detoxification through biological systems which remove or repair the damage may cause the production of peroxides and free radicals that damage all cell components, including proteins, lipids and ADN. The study's aim was the test, using the analysis of plasma samples' the use of lipid peroxidation by thiobarbituric acid reactive substances (TBARS), protein damage by carbonyl assay, non-enzymatic antioxidant defenses by sulfhydryl (SH) content, antioxidant enzymatic defenses by catalase (CAT) and superoxide dismutase (SOD), from patients with GD type I patients who received no prior treatment. Blood samples were collected from 10 patients previously diagnosed with GD type I and from 11 healthy subjects. Chitotriosidase (CT) activity was measured in plasma and the activity of β-glucosidase (GBA) was measured in leukocytes. The results showed a significant increased (p < 0.005) in GD samples when compared to healthy controls in CAT, SOD and SH, but there was no change in TBARS and carbonyl in the comparison between the two groups. In conclusion, the present data indicates the increased levels of enzymatic and non-enzymatic defenses without any effect on lipid peroxidation and damage to proteins. We believe that the results of this study are relevant to understanding the cellular changes involved in this important LSDs.

Α-Glucosidase Deficiency Promotes Increasing Protein Oxidative Damage in Pompe Disease Patients

“…The data found in TBARS, corroborated by the literature, shows the difference in the values between the groups studied [26]. These results confirm the findings obtained by this group in a previous study [31], which also showed no significant difference in the parameter between patients with Gaucher's Disease and healthy controls, showing that the cells seem to use another form of stress management in patients with enzyme deficiency.…”

Redox regulation of autophagy in skeletal muscle

“…While a certain level of ROS is essential for the regulation of cell growth and various biological functions, a disrupted ROS balance has negative implications. For example, oxidative stress has been associated with a number of pathological conditions, including neurodegenerative disorders (13–18), skeletal muscle disorders (19–23), lysosomal storage disorders (24, 25), cardiomyopathy (26, 27), carcinogenesis (28, 29), atherosclerosis (30, 31), diabetes (32, 33), and aging (34, 35). While the involvement of oxidative stress is firmly demonstrated in these pathological conditions, the specific source of ROS generation and the mechanisms by which each disease is regulated by ROS has yet to be elucidated.…”

Patients with Gaucher disease display systemic oxidative stress dependent on therapy status

“…However, alterations in other markers were less conclusive and untreated individuals were not evaluated. Mello et al reported that, on average, SOD and catalase activities were higher in ten treatment naïve GD1 patients (age range 3–46 years) when compared to healthy controls [ 19 ]. However, they did not observe any differences in MDA and protein carbonyl levels.…”

“…It is generally believed that these chronic complaints may reflect unabated inflammation associated with release of pro-inflammatory cytokines and other mediators either directly from Gaucher macrophages or indirectly by crosstalk between Gaucher cells and immunomodulatory lymphocytes [ 12 , 24 , 25 ]. However, it has also been hypothesized that accumulation of toxic glycosphingolipids within cells leads to the production of reactive oxygen species (ROS) and an imbalance between the pro-oxidants and the antioxidant reserve, resulting in oxidative stress and inflammation [ 19 ].…”

“…Inhibition of GCase activity also led to mitochondrial dysfunction and free radical damage in a human dopaminergic cell line [ 6 ]. There is also emerging evidence of systemic oxidative stress in patients with GD1 [ 19 , 29 ]. We designed a study to systematically evaluate oxidative stress biomarkers in participants with GD1 at three independent time points.…”