Glutathione redox cycle in small intestinal mucosa and peripheral blood of pediatric celiac disease patients

Abstract

The celiac disease is an autoimmune gastrointestinal disorder caused by gluten from wheat, rye or barley. In genetically predisposed persons, gluten induces the immune-mediated inflammation of small intestinal mucosa. Histological lesions include intraepithelial lymphocytosis, crypt hypertrophy and villous atrophy, resulting in malabsorption of micro-and macronutrients. The only treatment for celiac patients is a permanent gluten-free diet (GFD). Reactive oxygen species (ROS) and oxidative stress are strongly associated with the celiac disease. Glutathione (GSH) is a main detoxifier of endogenous and exogenous ROS in the intestine. In order to explain the role of glutathione redox cycle in celiac patients, we examined the activities of GSHrelated antioxidant (AO) enzymes glutathione peroxidase (GPx) and glutathione reductase (GR), as well as the concentration of GSH in small intestinal biopsies and peripheral blood of children affected by the celiac disease. The concentration of lipid hydroperoxides (LOOH) as markers of oxidative damage was measured in the same samples. The results clearly demonstrate a significant malfunction of GSH redox cycle with a concomitant decrease in the capacity to regenerate GSH and detoxify LOOH in celiac patients, even after several years of GFD. The oral administration of GSH and a diet rich in natural antioxidants, as well as appropriate dietary supplements, could be of great benefit to the patients.

Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences

“…Consistently, brain GSH levels are also reported to be decreased in autism (9) and schizophrenia (10), strongly supporting the proposal that a deficit in this specific antioxidant, namely GSH, might contribute to neurodevelopmental and neuropsychiatric disorders. Notably, intestinal mucosa and plasma levels of GSH are also reduced in pediatric celiac disease patients (11). Moreover, in few cases, patients with neurological conditions (12) like autism (13) and schizophrenia (14) also report a co-morbid problem of celiac disease and/or gut inflammation.…”

Alterations in serum levels of selected markers of oxidative imbalance in adult celiac patients with extraintestinal manifestations - pilot study

“…In subsequent papers, the same authors reported that GPx activity in the small intestine was also significantly lower in children with untreated and silent CD than in controls, and they showed a positive correlation between GPx activity and both GR and GSH concentrations. 13,27 To the best of our knowledge, no previous research has investigated serum GPx3 levels in adult celiac patients. In agreement with the above data, our results demonstrated a decreased activity of this antioxidant enzyme in the celiac group when compared with controls.…”

“…The activity of GPx depends on the availability of GSH and selenium, the depletion of which was reported in celiac patients. 13,26,27 It appears that a reduction in GSH and selenium levels is followed by a decrease in GPx activity.…”

“…Earlier studies also showed that the activity of SOD is markedly increased in pediatric patients with CD, while the activity of GPx is significantly decreased. 13 Interestingly, studies concerning the activity of GPx, as most studies on the role of OS in CD, have been conducted Serum UA concentrations were elevated only in celiac patients: in 4 patients (7.5%) with active CD and in 4 patients (4.3%) on GFD. UA levels were higher in the celiac groups than in controls (P <0.001), while bilirubin levels were lower in patients with active CD than in controls (P <0.05).…”

Evaluation of glutathione peroxidase and superoxide dismutase enzyme polymorphisms in celiac disease patients

“…Furthermore, the impairement of redox equilibrium was shown to cause severe damage in proteins and lipids (Preedy et al, 1998). Earlier studies have also noted that the activity of superoxide dismutase (SOD), an antioxidant enzyme, markedly increases in CD, whereas the activity of glutathione peroxidase (GSH-Px), another antioxidant enzyme, decreases significantly (Stojiljković et al, 2012). Improvements in technology have enabled genome studies to correlate oxidative stress with the development of genetic diseases.…”