Both overt (OHT) and subclinical hypothyroid (SHT) disorders have been found to be associated with increased oxidative stress (OXS). Excess thyrotropin [thyroid stimulating hormone (TSH)] is known to directly produce OXS. Increased lipid peroxidation is known to facilitate protein carbonylation. However, the associations between lipid and protein oxidation and elevated TSH levels have not been studied. Thyroid profile, lipid peroxidation as malondialdehyde (MDA) levels and protein carbonylation as protein carbonyls (PCO) were estimated in OHT and SHT groups consisting of 36 patients each, in comparison to 39 euthyroid controls. We also determined the associations between TSH, MDA, and PCO levels in OHT and SHT groups. Increased oxidative damage was evidenced through significant elevations in the concentrations of MDA and PCO in OHT and SHT groups compared to controls (p < 0.01). Both TSH and MDA levels were positively associated with PCO in OHT group. Partial correlation analysis revealed that both excess TSH and increased MDA levels are mutually influencing elevated PCO. The results indicate that there is a simultaneous oxidative damage to lipids and proteins leading to increased MDA and PCO levels in both patient groups. Either of the excess TSH and increased MDA levels are combinably involved in the elevation of PCO in hypothyroidism.
Oxidative stress as a result of disequilibrium between free radical generation and antioxidant status has been implicated in several pathologies including thyroid diseases. Studies on antioxidant status in overt (OHT) and subclinical hypothyroidism (SHT) are controversial and limited. The aim of this study was to determine the effect of OHT and SHT on antioxidant status. Thirty-six patients with OHT, 36 patients with SHT, and 39 healthy euthyroid subjects as the control group were included in the study. Plasma levels of malondialdehyde (MDA), reduced glutathione (GSH) and total antioxidant capacity (TAC) as ferric reducing ability of plasma (FRAP), and erythrocyte antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), SOD/GPx ratios, catalase (CAT), and glutathione reductase (GR) were analyzed in all groups. MDA and GPx values were elevated, while GSH, FRAP, SOD, and SOD/GPx ratio were decreased in both patient groups compared with controls. No change in activities of CAT and GR were observed in both the patient groups. Significant differences were observed between OHT and SHT groups with high MDA, GPX and low GSH, FRAP, SOD, and SOD/GPx ratio in OHT group. Thus, hypothyroid patients have a deficient antioxidant defense in the form of decreased activity of SOD, decreased levels of FRAP and GSH along with an increase in GPx activity. The severity of the disease appears to decide the degree of deficiency and our findings also point to this, in the form of decrease in SOD, FRAP, and GSH observed being more in OHT than in SHT patients. Hormonal changes and increased lipid peroxidation, which also vary with severity of disease, appear to contribute to the antioxidant deficiency.
Increase of MDA and IMA levels with decreased antioxidant status indicate the presence of OS in hypothyroid patients, which was more pronounced in OHT patients. Elevated levels of IMA can be a clinically useful marker of protein oxidative damage and OS in hypothyroidism.
Inflammation is a common feature of end-stage renal disease. Although there is evidence for hemodialysis (HD)-induced inflammatory process, the effect of a dialysis session on changes in inflammatory markers is still unclear. Seventeen patients of end-stage renal disease on maintenance HD along with 20 age-matched and sex-matched healthy controls were recruited after informed consent. C-reactive protein (CRP) and lipoprotein-associated phospholipase A2 (LpPLA2) activity were measured in the study and control groups. Intradialytic in CRP and LpPLA2 were studied. Comparison of pre-HD vs. the control group and predialytic and postdialytic values was performed using the Mann-Whitney U test and Wilcoxon's test, respectively. Statistical evaluation of intradialytic changes in inflammatory markers was performed using Friedman's test. Hemodialysis patients had higher CRP levels compared with controls (P=0.001). Post-HD LpPLA2 activity (n=17) was higher (P=0.039) compared with the pre-HD activity. Intradialytic changes in inflammatory markers showed a significant increase (P=0.012) in LpPLA2 activity (n=7), while no change (P=0.133) was observed in CRP levels (n=17). Evidence on the pro-inflammatory state being initiated by dialysis is provided by increased LpPLA2 activity. This may add to the atherogenic mileu and cause endothelial dysfunction in this high-risk group. Drugs that inhibit the LpPLA2 pathway have been developed and may be effective in these patients.
Several cardiovascular disease (CVD) risk factors have been identified among patients with chronic kidney disease (CKD). Gut-derived uremic toxins (GDUT) are important modifiable contributors in this respect. There are very few Indian studies on GDUT changes in CKD. One hundred and twenty patients older than 18 years diagnosed with CKD were enrolled along with forty healthy subjects. The patients were classified into three groups of forty patients based on stage of CKD. Indoxyl sulfate (IS), para cresyl sulfate (p-CS), indole acetic acid (IAA), and phenol were estimated along with the assessment of oxidative stress (OS), inflammatory state, and bone mineral disturbance. All the GDUT increased across the three groups of CKD. All patients had higher levels of malondialdehyde (MDA), ferric reducing ability of plasma (FRAP), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) as compared to controls. IS and IAA showed positive association with MDA/FRAP corrected for uric acid, whereas IS and p-CS showed positive association with IL-6. IS, IAA, and phenol showed a positive association with calcium × phosphorus product. GDUT increase OS and inflammatory state in CKD and may contribute to CVD risk.
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