Author, year [reference] Study design/country Population (age, sex)/sample size Biological sample/other markers Main outcome Results Conclusion Németh I. 1994 [31 ] Prospective longitudinal/Hungary Infants (gestational age 26-34 weeks, both sexes)/25 newborn premature infants with IRDS Blood/none GSSG/GSH in the blood could be an index of O2 toxicity in pathological status of premature newborns. Premature infants with IRDS have GSSG/GSH ratio higher than control newborns. A negative correlation between the redox ratio and the arterio-alveolar oxygen ratio was found. It is recommended the use of the blood GSSG/GSH ratio as a noninvasive measure of in vivo OS. Papp A. et al., 1999 [32 ] Cross-sectional/Hungary Infants who had been born prematurely (6 weeks-6 y, both sexes)/12 infants with active ROP Erythrocyte/none Glutathione status of erythrocytes in patients with retinopathy of prematurity (ROP) Infants with active disease have the highest GSSG/GSH ratio. The GSSG/GSH ratio may be a screen for active ROP in premature infants. Annuk M. et al., 2001 [58 ] Cross-sectional/Sweden Adults ( Serum/CD, MDA, LOOH, TAA, LPF Relationship between OS and endothelial function in chronic renal failure (CRF) The GSSG/GSH ratio was lower in patients with CRF. Endothelium-dependent vasodilation was negatively correlatedGSSG/GSH. The authors did not conclude directly about the ratio, but they assume that this ratio is a marker of OS. Sáez GT. et al., 2004 [59 ] Observational prospective of antihypertensive treatment/Spain Adults (mean 46 y, both sexes)/36 subjects with β -blockers Blood, peripheral mononuclear cells/MDA Impact of antihypertensive treatments on OSOS After 3 months of antihypertensive treatment, the GSSG/GSH ratio was reduced; the beneficial effect of treatment increases over time. The authors did not conclude directly about the ratio. Antihypertensive treatment improved the increased OS. Skalicky J. et al., 2008 [60 ] Cross-sectional/Czech Republic Adults ( Blood/TAS, vit. E, MDA, allantoin, α 1 -AP OS in obesity with and without metabolic syndrome (MetS) The obese patients with MetS have the highest GSSG/GSH ratio. The authors did not conclude directly about the ratio, but they indicate that imbalance oxidative/antioxidative status is a risk in obese adults. Lind L. et al., 2008 [61 ] Prospective study/Sweden Older adults (70 y, both sexes)/1016 subjects Serum/CD, ox-LDL, TAC, homocysteine Relationship between OS and brachial artery intima-media thickness (IMT) and grey scale median of the intima-media complex (IM-GSM) The GSSG/GSH ratio was related to brachial artery IM-GSM after adjustment of traditional risk factors and inflammatory markers. The low levels of the ratio indicate a reduced antioxidant activity. Mercken EM. et al., 2009 [62 ] Experimental/Netherlands Adults ( Erythrocyte/MDA, uric acid OS is differentially triggered by contracting peripheral muscles in COPD patients compared with controls GSSG/GSH ratio tended to be increased in COPD patients and tended to be increased immediately after exercise. The authors did not conclude directly about the ratio, although they discuss that the ratio slightly increased in COPD patients after exercise. Real JT. et al., 2010 [63 ] Cross-sectional/Spain Adults ( Circulating mononuclear cells (CMC)/MDA, XO, SOD, CAT, GPx Analyze the OS levels in CMC from familiar hypercholesterolemia (HF) patients and controls GSSG/GSH ratio was significantly higher in FH patients compared with controls. The authors did not conclude directly about the ratio, but they affirm that there is an important alteration of OS regulation in FH. Rusanova I. et al., 2010 [64 ] Cross-sectional/Panama Children (6 months-15 y, both sexes)/95 patients with SCD Erythrocyte/MDA, 4-HNE, NOx, GPx, GR, SOD To correlate β -globin gene haplotypes with the OS in pediatric patients with sickle cell disease (SCD) GSSG/GSH ratio was higher in patients with SCD. Based on the ratio, the findings support the existence of oxidative damage in sickle cells. Petrillo S. et al., 2013 [65 ] Cross-sectional/Italy All (4-64 y, does not specify sex)/14 patients with X-ALD Lymphocyte Define the role of the glutathione in X-linked adrenoleuko-dystrophy (X-ALD) The GSSG/GSH ratio was increased in patients with adrenomyelo-neuropathy. The balance among glutathione forms is a hallmark and a potential biomarker of the X-ALD. De Tursi Ríspoli L. et al., 2013 [66 ] Observational prospective of bariatric surgery/Spain Adults ( Erythrocyte/MDA, 8-oxo-dG Assessment of OS variations and its relationship with the weight loss after a duodenal crossing surgical The GSSG/GSH ratio diminished across one year from 3 months after the surgery. The authors did not conclude directly about the ratio, but they infer that weight loss improves antioxidant status. Bagan J. et al., 2014 [56 ] Observational/Spain Adults ( Serum Changes of OS in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) The GSSG/GSH ratio was a prognostic factor for the development of BRONJ after adjusted by confounders. The GSSG/GSH was a significant factor predicting the development of BRONJ. Blasco H. et al., 2017 [67 ] Preliminary study/France Adults ( Blood/MDA, 8-OHdG, TAS Association of OS and amyotrophic lateral sclerosis (ALS) Higher GSSG/GSH ratio in ALS patients and correlations were found between the ratio and clinical markers. The systemic alteration of the redox status in ALS patients was confirmed. Arana C. et al., 2017 [57 ] Observational/Spain Adults (18-65 y, both sexes)/24 patients with T2DM and good metabolic control Saliva/GPx, GR Association between OS and periodontal disease in type 2 diabetes mellitus (T2DM) patients Both diabetic groups showed higher GSSG/GSH quotients, being higher ratio in diabetic patients with poor metabolic control. Poor metabolic control in T2DM patients is associated with higher levels of salivary OS. Bellanti F. et al., 2018 [68 ] Population-based cross-sectional study/Italy Older adults ( Blood/MDA, 4-HNE Association between OS and sarcopenic obesity in terms of glutathione balance Sarcopenic had GSSG/GSH ratio higher than nonsarcopenic patients. There is a strong association between the Framingham CVD risk and GSSG/GSH in the sarcopenic-obese patients. Redox balance analysis would be a useful part of a multidimensional evaluation in aging.
