The Inflammatory and Oxidative Status of Newly Diagnosed Class III and Class IV Lupus Nephritis, with Six-Month Follow-Up.

Lupus nephritis (LN) is the most frequent and severe complication of systemic lupus erythematosus (SLE). A prospective cohort with a six-month follow-up was performed. Twelve SLE patients diagnosed with LN Class III, twelve NL Class IV patients, and twelve healthy control subjects (HC) were included. SLE data, renal function, oxidants, antioxidants, and inflammation were determined at baseline and six-month follow-up. During the six-month follow-up, the SLE Disease Activity Index (SLEDAI-2K) decreased in both LN Class III (20.08 ± 6.92 vs. 11.92 ± 5.87, p < 0.001) and LN Class IV (25.33 ± 6.01 vs. 13.83 ± 5.52, p < 0.001) patients. Furthermore, the values of the C4 component also increased during follow-up for LN Class III (25.36 ± 6.34 vs. 30.91 ± 9.22, p = 0.027) and LN Class IV (12.18 ± 3.90 vs. 20.33 ± 8.95, p = 0.008) groups. Regarding inflammation markers, both groups presented decreased C-reactive protein (CRP), but this was only significant for patients with LN class III (7.93 ± 1.77 vs. 4.72 ± 3.23, p = 0.006). Renal function remained stable in both groups, with no changes in eGFR. Patients with LN Class III and Class IV showed higher baseline levels for lipoperoxides (Class III p < 0.01, Class IV p < 0.1) and carbonyl groups in proteins (Class III p < 0.01, Class IV p < 0.1) compared to HC. Moreover, both groups presented lower baseline values of total antioxidant capacity (Class III p < 0.01, Class IV p < 0.1) and catalase (Class III p < 0.01, Class IV p < 0.1) compared to HCs. However, antioxidant and oxidant markers did not show significant differences between baseline values and at six months for either of the two study groups. In conclusion, patients show an imbalance in the oxidative state characterized by the increase in the oxidants LPO and protein carbonyl groups and the decrease in the activity of the antioxidant enzymes TAC and CAT compared to HC. However, the patients did not present an increase in disease activity and renal function improvement. The glomerular filtration rate did not change during the length of the study, and SLEDAI -2K, C3, and C4 improved. The early co-management between Rheumatologists and Nephrologists is essential to prevent the rapid progression of LN. It would be interesting to administer antioxidant supplements to patients with a recent diagnosis of LN and evaluate its effect in a follow-up study.

The Role of the Oxidative State and Innate Immunity Mediated by TLR7 and TLR9 in Lupus Nephritis.

Lupus nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) and is considered one of the leading causes of mortality. Multiple immunological pathways are involved in the pathogenesis of SLE, which makes it imperative to deepen our knowledge about this disease's immune-pathological complexity and explore new therapeutic targets. Since an altered redox state contributes to immune system dysregulation, this document briefly addresses the roles of oxidative stress (OS), oxidative DNA damage, antioxidant enzymes, mitochondrial function, and mitophagy in SLE and LN. Although adaptive immunity's participation in the development of autoimmunity is undeniable, increasing data emphasize the importance of innate immunity elements, particularly the Toll-like receptors (TLRs) that recognize nucleic acid ligands, in inflammatory and autoimmune diseases. Here, we discuss the intriguing roles of TLR7 and TLR9 in developing SLE and LN. Also included are the essential characteristics of conventional treatments and some other novel and little-explored alternatives that offer options to improve renal function in LN.

Oxidation State in Peritoneal Dialysis in Patients with Type 2 Diabetes Mellitus.

End-stage renal disease (ESRD) progression is closely related to oxidative stress (OS). The study objective was to determine the oxidant and antioxidant status in peritoneal dialysis (PD) patients with type 2 diabetes mellitus (DM). An analytical cross-sectional study from the PD program was carried out with 62 patients, 22 with and 40 without DM. Lipoperoxides (LPO) levels in patients with DM, 3.74 ± 1.09 mM/L, and without DM, 3.87 ± 0.84 mM/L were found to increase compared to healthy controls (HC) 3.05 ± 0.58 mM/L (p = 0.006). The levels of the oxidative DNA damage marker (8-OH-dG) were found to be significantly increased in patients with DM, 1.71 ng/mL (0.19-71.92) and without DM, 1.05 ng/mL (0.16-68.80) front to 0.15 ng/mL (0.15-0.1624) of HC (p = 0.001). The antioxidant enzyme superoxide dismutase (SOD) activity was found to be significantly increased in patients with DM, 0.37 ± 0.15 U/mL, and without DM, 0.37 ± 0.17 compared to HC, 0.23 ± 0.05 U/mL (p = 0.038). The activity of the enzyme glutathione peroxidase (GPx) showed a significant increase (p < 0.001) in patients with DM, 3.56 ± 2.18 nmol/min/mL, and without DM, 3.28 ± 1.46 nmol/min/mL, contrary to the activity obtained in HC, 1.55 ± 0.34 nmol/min/mL. In conclusion, we found an imbalance of oxidative status in patients undergoing PD with and without DM through the significant increase in LPO oxidants and the marker of oxidative damage in DNA. The activity of the antioxidant enzymes SOD and GPx were significantly increased in patients with and without DM undergoing PD, possibly in an attempt to compensate for the deregulation of oxidants. Antioxidant enzymes could be promising therapeutic strategies as a complement to the management of chronic kidney diseases.

Prevalence of Hypertension and Obesity: Profile of Mitochondrial Function and Markers of Inflammation and Oxidative Stress.

Obesity and hypertension are health problems of increasing prevalence in developed countries. The link between obesity and hypertension is not yet fully determined. Oxidative stress (OS) and mitochondrial function may play a role in obesity-associated hypertension. A cross-sectional study with 175 subjects with normal weight, overweight, or obese who attended a medical check-up was included. The subjects were divided according to the body mass index (BMI) into normal-weight (n-53), overweight (n-84), and obesity (n-38). Hypertension was also evaluated. To measure mitochondrial function, ATP hydrolysis and ATP synthesis in platelets and serum, respectively, were determined. Superoxide dismutase (SOD), catalase, lipohydroperoxides, 8-isoprostanes, carbonyl groups in proteins, nitric oxide (NO) metabolites, 8-hydroxy-2'-deoxyguanosine (8-OHG), 8-oxoguanine glycosylase (hOGG1), tumor necrosis factor-alpha (TNF-α) and interleukin 6 (IL-6) were measured by standard colorimetric or immunoassay methods. Obese subjects showed lower ATP hydrolysis activity than normal weight and overweight subjects (p < 0.01). No differences between those groups were found in ATP synthase and catalase activities, lipid hydroperoxides, carbonyl groups in proteins, 8-isoprostanes, and NO metabolites. In the obesity group, SOD activity (p < 0.01) was decreased while 8-OHG (p < 0.01) was increased. Subjects with hypertension showed increased 8-OHG (p < 0.01) and less reparative enzyme (hOGG1 p = 0.04) than subjects with normal weight. Moreover, we found a decrease of SOD (p < 0.01), catalase activities (p = 0.04), NO metabolites (p < 0.01), and increases of carbonyl groups in proteins (p = 0.01), TNF-α (p < 0.01) and IL-6 (p < 0.01 in hypertensive subjects. Obese subjects show a decrease in ATP hydrolysis. The decrease in ATP hydrolysis rate and ATP synthesis and an increase in OS and inflammation markers were associated with the hypertensive state.

The Influence of the Severity of Early Chronic Kidney Disease on Oxidative Stress in Patients with and without Type 2 Diabetes Mellitus.

Early Chronic Kidney Disease (CKD) is a condition that tends to progress to End-Stage Kidney Disease (ESKD). Early diagnosis of kidney disease in the early stages can reduce complications. Alterations in renal function represent a complication of diabetes mellitus (DM). The mechanisms underlying the progression of CKD in diabetes could be associated with oxidative and inflammatory processes. This study aimed to evaluate the state of inflammation and oxidative stress (OS) on the progression of CKD in the early stages in patients with and without type 2 diabetes mellitus (T2DM). An analytical cross-sectional study was carried out in patients with CKD in early stages (1, 2, 3) with and without T2DM. The ELISA method determined the expression of pro-inflammatory cytokines IL-6 and TNF-α as well as lipoperoxides (LPO), nitric oxide (NO), and superoxide dismutase activity (SOD). Colorimetric methods determined glutathione peroxidase (GPx) and total antioxidant capacity (TAC). Patients with CKD and T2DM had significantly decreased antioxidant defenses for SOD (p < 0.01), GPx (p < 0.01), and TAC (p < 0.01) compared to patients without T2DM. Consequently, patients with T2DM had higher concentrations of oxidant markers, NO (p < 0.01), inflammation markers, IL-6 (p < 0.01), and TNF-α than patients without T2DM. CKD stages were not related to oxidative, antioxidant, and inflammatory marker outcomes in T2DM patients. Patients without T2DM presented an increase in SOD (p = 0.04) and a decrease in NO (p < 0.01) when the stage of CKD increased. In conclusion, patients with T2DM present higher levels of oxidative and inflammatory markers accompanied by a decrease in antioxidant defense. However, these oxidative status markers were associated with CKD stage progression in patients without T2DM. Thus, NO and SOD markers could help detect the early stages of CKD in patients who have not yet developed metabolic comorbidities such as T2DM.

The Effect of Enalapril, Losartan, or Not Antihypertensive on the Oxidative Status in Renal Transplant Recipients.

The clinical and biochemical improvement observed in kidney transplant (RT) recipients is remarkable. The correct functioning of the allograft depends on various factors such as the donor's age, the alloimmune response, the ischemia-reperfusion injury, arterial hypertension, and the interstitial fibrosis of the allograft, among others. Antihypertensive drugs are necessary for arterial hypertension patients to avoid or reduce the probability of affecting graft function in RT recipients. Oxidative stress (OS) is another complex pathophysiological process with the ability to alter posttransplant kidney function. The study's objective was to determine the effect of the administration of Enalapril, Losartan, or not antihypertensive medication on the oxidative state in RT recipients at the beginning of the study and one year of follow-up. All patients included in the study found significant overexpression of the oxidative damage marker to DNA and the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx). In contrast, it was found that the determination of the total antioxidant capacity decreased significantly in the final determination at one year of follow-up in all the patients who ingested Enalapril and Losartan. We found dysregulation of the oxidative state characterized mainly by oxidative damage to DNA and a significant increase in antioxidant enzymes, which could suggest a compensatory effect against the imbalance of the oxidative state.

The Influence of Sevelamer Hydrochloride and Calcium Carbonate on Markers of Inflammation and Oxidative Stress in Hemodialysis at Six Months of Follow-Up.

Patients with end-stage renal disease (ESRD) present alterations in mineral and bone metabolism. Hyperphosphatemia in ESRD is considered an independent risk factor for cardiovascular disease (CVD), increasing morbidity, and mortality. Sevelamer hydrochloride is a calcium-free, non-absorbable phosphate-chelating polymer. Calcium carbonate chelator is helpful in controlling serum phosphate levels. There is insufficient information on the influence of sevelamer hydrochloride and calcium carbonate on the behavior of oxidative stress (OS) markers and inflammation in patients on hemodialysis (HD). A randomized open clinical trial was carried out on patients to evaluate sevelamer hydrochloride and calcium carbonate influence at 6 months of study follow-up. Levels of oxidants (LPO, NO, and 8-isoprostanes), antioxidants (SOD and TAC), oxidative DNA damage (8-OHdG and hOGG1), pro-inflammatory cytokines (IL-6 and TNF-α), and inflammation markers (ferritin and C-reactive protein) were measured with colorimetric and ELISA methods. We found a significant increase in oxidants LPO and NO, and antioxidants SOD and TAC, and downregulation of IL-6 and TNF-α. Ferritin decrease at 6 months follow-up in the sevelamer hydrochloride group. Increase in C-reactive protein was found in the group of patients treated with calcium carbonate. In conclusion, we found an oxidative state imbalance with increase in LPO and NO oxidants. The activity of the antioxidant enzymes (SOD and TAC) was also found to increase, suggesting a compensatory effect in the face of increase in oxidants. The same phenomenon was observed with increase in the oxidative damage marker to DNA and the increase in the DNA repair enzyme, suggesting a compensatory effect. Pro-inflammatory cytokines were predominantly downregulated by TNF-α in the group that ingested sevelamer hydrochloride in the final determination at 6 months of follow-up. Serum ferritin levels decreased significantly at the end of follow-up in patients on HD in the sevelamer hydrochloride group. The management of hyperphosphatemia with sevelamer hydrochloride appears to have obvious anti-inflammatory and antioxidant benefits.

Green Tea Extract Increases Soluble RAGE and Improves Renal Function in Patients with Diabetic Nephropathy.

One of the proposed mechanisms for the development of diabetic nephropathy (DN) is the increase of end products of advanced glycosylation (AGEs), which bind to its receptor (RAGE), favoring nephron cellular damage. An isoform of this receptor is soluble RAGE (sRAGE), which can antagonize AGE-altered intracellular signaling. It has known that green tea extract (GTE) increases the expression of sRAGE, but it is unknown whether this could improve kidney function. The objective of this study was to evaluate the effect of the administration of GTE on the concentrations of sRAGE, renal function, and metabolic profile in patients with type 2 diabetes mellitus (T2DM) and DN. A randomized, double-blinded, placebo-controlled clinical trial was carried out in 39 patients who received GTE (400 mg every 12 h) or placebo for 3 months. sRAGE levels, renal function, and metabolic parameters were determined before and after the intervention. In the GTE group, there were statistically significant increase on sRAGE (320.55 ± 157.63 pg/mL vs. 357.59 ± 144.99 pg/mL; P = .04) and glomerular filtration rate (GFR; 66.44 ± 15.17 mL/min/1.73 m2 vs. 71.70 ± 19.33 mL/min/1.73 m2; P = .04), and a statistically significant decrease in fasting serum glucose (7.62 ± 3.00 mmol/L vs. 5.86 ± 1.36 mmol/L; P ≤ .01) and triacylglycerols (1.91 ± 0.76 mmol/L vs. 1.58 ± 0.69; P = .02). Administration of GTE increases the serum concentration of sRAGE and the GFR and decreases the concentration of fasting serum glucose and triacylglycerols. The study was registered in ClinicalTrials.gov with the identifier NCT03622762.

The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases.

Oxidative stress (OS) has the ability to damage different molecules and cellular structures, altering the correct function of organs and systems. OS accumulates in the body by endogenous and exogenous mechanisms. Increasing evidence points to the involvement of OS in the physiopathology of various chronic diseases that require prolonged periods of pharmacological treatment. Long-term treatments may contribute to changes in systemic OS. In this review, we discuss the involvement of OS in the pathological mechanisms of some chronic diseases, the pro- or antioxidant effects of their pharmacological treatments, and possible adjuvant antioxidant alternatives. Diseases such as high blood pressure, arteriosclerosis, and diabetes mellitus contribute to the increased risk of cardiovascular disease. Antihypertensive, lipid-lowering, and hypoglycemic treatments help reduce the risk with an additional antioxidant benefit. Treatment with methotrexate in autoimmune systemic inflammatory diseases, such as rheumatoid arthritis, has a dual role in stimulating the production of OS and producing mitochondrial dysfunction. However, it can also help indirectly decrease the systemic OS induced by inflammation. Medicaments used to treat neurodegenerative diseases tend to decrease the mechanisms related to the production of reactive oxygen species (ROS) and balance OS. On the other hand, immunosuppressive treatments used in cancer or human immunodeficiency virus infection increase the production of ROS, causing significant oxidative damage in different organs and systems without widely documented exogenous antioxidant administration alternatives.

The Alteration of Pro-inflammatory Cytokines and Oxidative Stress Markers at Six-Month Post-living Kidney Donation.

Donors have a higher risk of developing chronic kidney disease than the general population. Some mechanisms mediated by pro-inflammatory cytokines and oxidative stress may be involved as risk factors. The objective of the study was to evaluate the behavior of pro-inflammatory cytokines and oxidative stress markers in living renal donors with a 6-month follow-up. A single prospective cohort was performed in 88 renal donors. At the end of the follow-up, the levels of lipoperoxides, 6.52 ± 1.12 mM, and 8-isoprostanes, 63.75 ± 13.28 pg/mL, were lower than before donation, 10.20 ± 3.95 mM (p < 0.001) and 67.54 ± 9.64 pg/mL (p = 0.026), respectively. Initial levels of nitric oxide (NO), 356.09 ± 59.38 µM increased at the end of the follow-up, 467.08 ± 38.74 µM (p < 0.001). It was observed in the final determination of donors decreased activity of antioxidant enzymes superoxide dismutase (SOD), 0.74 ± 0.57 U/L and glutathione peroxidase (GPx), 556.41 ± 80.37 nmol, in comparison with the levels obtained in the initial determination, 1.05 ± 0.57 U/L (p < 0.001) and 827.93 ± 162.78 nmol (p < 0.001), respectively. The pro-inflammatory cytokines, Tumor necrosis factor alpha and interleukin-6 showed no differences at 6 months after donation. The enzyme oxoguanine glycosylase (hOGG1) responsible for repairing oxidative damage to DNA, showed a decrease in its concentration at the end of the study in donor men, 0.40 ± 0.21 ng/mL compared to the initial levels, 0.55 ± 0.32 ng/mL (p = 0.025). The marker, 8-hydroxy-2-deoxyguanosine (8-OHdG) exhibited an increase in donor men at the final determination 2.28 ± 1.99 ng/mL, compared to the concentration before donation, 1.72 ± 1.96 ng/mL (p < 0.001). We found significant changes in the markers of the oxidative state with increased NO and 8-OHdG, as well as a significant decrease in the antioxidant defenses SOD, GPx, and in the DNA repair enzyme in living renal donors after 6 months of follow-up.

Foods with Potential Prooxidant and Antioxidant Effects Involved in Parkinson's Disease.

Oxidative stress plays a fundamental role in the pathogenesis of Parkinson's disease (PD). Oxidative stress appears to be responsible for the gradual dysfunction that manifests via numerous cellular pathways throughout PD progression. This review will describe the prooxidant effect of excessive consumption of processed food. Processed meat can affect health due to its high sodium content, advanced lipid oxidation end-products, cholesterol, and free fatty acids. During cooking, lipids can react with proteins to form advanced end-products of lipid oxidation. Excessive consumption of different types of carbohydrates is a risk factor for PD. The antioxidant effects of some foods in the regular diet provide an inconclusive interpretation of the environment's mechanisms with the modulation of oxidation stress-induced PD. Some antioxidant molecules are known whose primary mechanism is the neuroprotective effect. The melatonin mechanism consists of neutralizing reactive oxygen species (ROS) and inducing antioxidant enzyme's expression and activity. N-acetylcysteine protects against the development of PD by restoring levels of brain glutathione. The balanced administration of vitamin B3, ascorbic acid, vitamin D and the intake of caffeine every day seem beneficial for brain health in PD. Excessive chocolate intake could have adverse effects in PD patients. The findings reported to date do not provide clear benefits for a possible efficient therapeutic intervention by consuming the nutrients that are consumed regularly.

The Effect of Visceral Abdominal Fat Volume on Oxidative Stress and Proinflammatory Cytokines in Subjects with Normal Weight, Overweight and Obesity.

PURPOSE: The increase of visceral abdominal fat (VAF) and oxidative stress (OS) are independent predictors for cardiovascular risk. This study aimed to determine the association of VAF with proinflammatory cytokines, oxidants, antioxidants, and oxidative damage to DNA in subjects with normal weight, overweight, and obesity. PATIENTS AND METHODS: A cross-sectional study that included 21 men and 71 women who attended for a medical check-up was conducted. Dual-energy X-ray absorptiometry (DXA) was used to measure the VAF volume. ELISA and colorimetric techniques were used for chemical analysis. RESULTS: Low activity of superoxide dismutase (SOD) was found in overweight and obese subjects compared to the normal weight group (p=0.005). In contrast, the activity of glutathione peroxidase (GPx) was higher in the overweight and obesity groups compared to the normal weight subjects (p=0.017). The total antioxidant capacity (TAC) was also increased in the overweight group compared to the normal weight group (p=0.04). According to the volume of VAF, the levels of tumor necrosis factor alfa and interleukin 6 showed no differences between subjects with normal and high VAF. Subjects with high VAF show higher levels of 8-isoprostans compared to normal VAF group (p=0.039). Less concentration of 8-oxoguanine-DNA-N-glycosylase-1 (hOGG1) was found in the high VAF group (p=0.032) compared to the normal VAF subjects. VAF was positively correlated with lipoperoxides (LPO) (r=0.27, p<0.05) and 8-isoprostanes (r=0.25, p<0.05). We also found correlations between oxidative stress markers and anthropometric ratios for intra-abdominal fat. The waist-hip ratio was positively correlated with LPO (r=0.30, p<0.05) and TAC (r=0.24, p<0.05). CONCLUSION: These findings suggest that the predominantly oxidative damage associated with VAF in overweight or obesity is lipoperoxidation and oxidative DNA damage. Alterations in endogenous antioxidant defenses may not be linked to the amount of VAF.

The Behavior of the Type of Peritoneal Transport in the Inflammatory and Oxidative Status in Adults Under Peritoneal Dialysis.

Peritoneal dialysis (PD) is an alternative for managing the end-stage renal disease (ESRD). The peritoneal membrane (PM) is not just a membrane that passively responds to diffusion and convection. The characteristics of PM result in the peritoneal equilibrium test (PET) and with this test is possible to obtain the type of peritoneal transport (PT). The patient on PD can be classified in different types of PT as; Low, Low Average, High Average, and High. The aim of the study was to compare the inflammatory cytokines, oxidants, antioxidants, and oxidative DNA damage markers in the different types of PT. A cross-sectional analytical study of 77 adult PD patients was performed. Levels of lipoperoxides (LPO) were higher in all types of PT vs. healthy volunteer controls (HC) (p < 0.0001). Nitric oxide (NO) levels were found significantly down-regulated in all types of PT (p < 0.0001). The activity of the superoxide dismutase enzyme (SOD) was found to be significantly increased in all types of PT vs. the HC (p < 0.0001). The levels of the DNA repair enzyme were found to be decreased in all types of PT. The levels of the pro-inflammatory cytokines TNF-α, IL-6, the marker of oxidative DNA damage, 8-IP and the total antioxidant capacity (TAC) were all significantly decreased, contrary to the levels in HC, possibly by the clearance in the dialysis fluid in all types of PT or due to down-regulation of their expression. In conclusion, we found significant changes in markers of inflammation, oxidative stress, and oxidative damage to DNA in all types of PT; Low, low average, high average, and high PT in the values of D/P creatinine at 4 h compared to HC.