RESUMO
Renal involvement is an important cause of morbidity and mortality in systemic lupus erythematosus (SLE). The present study included patients with recently diagnosed Class III and Class IV lupus nephritis (LN) treated by Rheumatology who, upon the detection of alterations in their kidney function, were referred to Nephrology for the joint management of both medical specialties. The purpose of this study was to compare the plasma expression of Toll-Like Receptor 7 (TLR7) and TLR9 in healthy control (HC) subjects and newly diagnosed Class III and Class IV LN patients with 12-month follow-ups. The plasma expression of TLR7 and TLR9 proteins was determined by the ELISA method. A significant increase in the expression of TLR7 protein was found in Class III LN in the basal determination compared to the expression in the HC (p = 0.002) and at 12 months of follow-up (p = 0.03) vs. HC. The expression of TLR9 showed a behavior opposite to that of TLR7. TLR9 showed decreased protein expression in LN Class III patients' baseline and final measurements. The result was similar in the basal and final determinations of LN Class IV compared to the expression in HC. A significant decrease in SLEDAI -2K was observed at 12 months of follow-up in patients in Class III (p = 0.01) and Class IV (p = 0.0001) of LN. Complement C3 levels improved significantly at 12-month follow-up in Class IV patients (p = 0.0001). Complement C4 levels decreased significantly at 12-month follow-up in LN Class III compared to baseline (p = 0.01). Anti-DNA antibodies decreased significantly at 12 months of follow-up in Class IV LN (p = 0.01). A significant increase in proteinuria was found at 12 months of follow-up in Class III LN, compared to the baseline determination (p = 0.02). In LN Class IV, proteinuria decreased at 12 months of follow-up compared to baseline (p = 0.0001). Albuminuria decreased at 12 months of follow-up in LN Class IV (p = 0.006). Class IV LN, albuminuria also decreased at 12 months of follow-up (p = 0.009). Hematuria persisted in all patients and the glomerular filtration rate did not change. Three Class IV patients died before 12 months of follow-up from various causes. In conclusion, although the rheumatologic data appeared to improve, the renal function data remained inconsistent. Decreased expression of TLR9 and increased expression of TLR7 could be useful in the early diagnosis of Class III and Class IV LN is correct.
Assuntos
Nefrite Lúpica , Receptor 7 Toll-Like , Receptor Toll-Like 9 , Humanos , Nefrite Lúpica/diagnóstico , Nefrite Lúpica/sangue , Nefrite Lúpica/metabolismo , Receptor 7 Toll-Like/metabolismo , Receptor 7 Toll-Like/genética , Receptor Toll-Like 9/metabolismo , Feminino , Adulto , Masculino , Seguimentos , Pessoa de Meia-Idade , Estudos de Casos e Controles , Adulto JovemRESUMO
Background: Cardiorenal syndrome (CRS) type 4 is prevalent among the chronic kidney disease (CKD) population, with many patients dying from cardiovascular complications. However, limited data regarding cardiac transcriptional changes induced early by CKD is available. Methods: We used a murine unilateral ureteral obstruction (UUO) model to evaluate renal damage, cardiac remodeling, and transcriptional regulation at 21 days post-surgery through histological analysis, RT-qPCR, RNA-seq, and bioinformatics. Results: UUO leads to significant kidney injury, low uremia, and pathological cardiac remodeling, evidenced by increased collagen deposition and smooth muscle alpha-actin 2 expression. RNA-seq analysis identified 76 differentially expressed genes (DEGs) in UUO hearts. Upregulated DEGs were significantly enriched in cell cycle and cell division pathways, immune responses, cardiac repair, inflammation, proliferation, oxidative stress, and apoptosis. Gene Set Enrichment Analysis further revealed mitochondrial oxidative bioenergetic pathways, autophagy, and peroxisomal pathways are downregulated in UUO hearts. Vimentin was also identified as an UUO-upregulated transcript. Conclusions: Our results emphasize the relevance of extensive transcriptional changes, mitochondrial dysfunction, homeostasis deregulation, fatty-acid metabolism alterations, and vimentin upregulation in CRS type 4 development.
RESUMO
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.
RESUMO
Evidence supporting a starting dose of 2 g/day of mycophenolate mofetil (MMF) in combination with tacrolimus (TAC) for renal transplantation (RT) is still limited, but maintaining a dose of <2 g could result in worse clinical outcomes in terms of acute rejection (AR). This study aimed to determine the association between AR and infectious and noninfectious complications after RT with a dose of 1.5 g vs 2 g of MMF. A prospective cohort study was performed with a 12-month follow-up of recipients of RT from living donors with low (1.5 g/day) or standard (2 g/day) doses of MMF. The association between adverse effects and complications and doses of MMF was examined using Cox proportional hazard models, and survival free of AR, infectious diseases, and noninfectious complications was evaluated using the Kaplan-Meier test. At the end of the follow-up, the incidence of infectious diseases was 52% versus 50% (P = .71) and AR was 5% versus 5% (P = .86), respectively. The survival rate free of gastrointestinal (GI) complications requiring medical attention was higher in the low-dose group than in the standard-dose dose (88% vs 45%, respectively; P < .001). The use of 1.5 g/day of MMF confers a reduction in GI complications without an increase in infectious diseases or the risk of AR.
Assuntos
Doenças Transmissíveis , Transplante de Rim , Humanos , Tacrolimo/efeitos adversos , Ácido Micofenólico/efeitos adversos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , México/epidemiologia , Estudos Prospectivos , Quimioterapia Combinada , Doenças Transmissíveis/etiologia , Hospitais , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/epidemiologia , Sobrevivência de EnxertoRESUMO
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.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Nefrite Lúpica/metabolismo , Receptor Toll-Like 9/metabolismo , Receptor 7 Toll-Like/genética , Imunidade Inata , OxirreduçãoRESUMO
Cardiovascular and renal diseases are among the leading causes of death worldwide, and regardless of current efforts, there is a demanding need for therapeutic alternatives to reduce their progression to advanced stages. The stress caused by diseases leads to the activation of protective mechanisms in the cell, including chaperone proteins. The Sigma-1 receptor (Sig-1R) is a ligand-operated chaperone protein that modulates signal transduction during cellular stress processes. Sig-1R interacts with various ligands and proteins to elicit distinct cellular responses, thus, making it a potential target for pharmacological modulation. Furthermore, Sig-1R ligands activate signaling pathways that promote cardioprotection, ameliorate ischemic injury, and drive myofibroblast activation and fibrosis. The role of Sig-1R in diseases has also made it a point of interest in developing clinical trials for pain, neurodegeneration, ischemic stroke, depression in patients with heart failure, and COVID-19. Sig-1R ligands in preclinical models have significantly beneficial effects associated with improved cardiac function, ventricular remodeling, hypertrophy reduction, and, in the kidney, reduced ischemic damage. These basic discoveries could inform clinical trials for heart failure (HF), myocardial hypertrophy, acute kidney injury (AKI), and chronic kidney disease (CKD). Here, we review Sig-1R signaling pathways and the evidence of Sig-1R modulation in preclinical cardiac and renal injury models to support the potential therapeutic use of Sig-1R agonists and antagonists in these diseases.
Assuntos
Doenças Cardiovasculares , Nefropatias , Receptores sigma , Humanos , Cardiomegalia , COVID-19/complicações , Insuficiência Cardíaca/complicações , Ligantes , Receptores sigma/agonistas , Receptores sigma/antagonistas & inibidores , Receptores sigma/genética , Receptores sigma/metabolismo , Transdução de Sinais/fisiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/metabolismo , Nefropatias/complicações , Nefropatias/genética , Nefropatias/metabolismo , Receptor Sigma-1RESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2 , Diálise Peritoneal , Humanos , Antioxidantes/metabolismo , Estudos Transversais , Superóxido Dismutase/metabolismo , Estresse Oxidativo , Peróxidos Lipídicos , Glutationa Peroxidase/metabolismo , OxidantesRESUMO
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.
RESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Glutationa Peroxidase/metabolismo , Humanos , Inflamação/metabolismo , Interleucina-6/metabolismo , Peróxidos Lipídicos , Óxido Nítrico , Oxidantes , Estresse Oxidativo , Insuficiência Renal Crônica/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
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.
Assuntos
Transplante de Rim , Losartan , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Enalapril/metabolismo , Enalapril/farmacologia , Enalapril/uso terapêutico , Humanos , Rim , Losartan/farmacologia , Losartan/uso terapêutico , Estresse OxidativoRESUMO
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.
RESUMO
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.
RESUMO
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.
Assuntos
Antioxidantes/uso terapêutico , Doença Crônica/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/farmacologia , HumanosRESUMO
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.
Assuntos
Antioxidantes/uso terapêutico , Microbiologia de Alimentos/métodos , Doença de Parkinson/dietoterapia , Espécies Reativas de Oxigênio/efeitos adversos , Antioxidantes/farmacologia , Dieta , HumanosRESUMO
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.
RESUMO
Chronic kidney disease (CKD) is highly incident and prevalent in the world. The death of patients with CKD is primarily due to cardiovascular disease. Renal transplantation (RT) emerges as the best management alternative for patients with CKD. However, the incidence of acute renal graft dysfunction is 11.8% of the related living donor and 17.4% of the cadaveric donor. Anticardiolipin antibodies (ACAs) or antiphospholipid antibodies (APAs) are important risk factors for acute renal graft dysfunction. The determination of ACA or APA to candidates for RT could serve as prognostic markers of early graft failure and would indicate which patients could benefit from anticoagulant therapy. Cardiolipin is a fundamental molecule that plays an important role in the adequate conformation of the mitochondrial cristae and the correct assembly of the mitochondrial respiratory supercomplexes and other proteins essential for proper mitochondrial function. Cardiolipin undergoes a nonrandom oxidation process by having pronounced specificity unrelated to the polyunsaturation pattern of its acyl groups. Accumulation of hydroxyl derivatives and cardiolipin hydroperoxides has been observed in the affected tissues, and recent studies showed that oxidation of cardiolipin is carried out by a cardiolipin-specific peroxidase activity of cardiolipin-bound cytochrome c. Cardiolipin could be responsible for the proapoptotic production of death signals. Cardiolipin modulates the production of energy and participates in inflammation, mitophagy, and cellular apoptosis. The determination of cardiolipin or its antibodies is an attractive therapeutic, diagnostic target in RT and kidney diseases.
Assuntos
Cardiolipinas/imunologia , Transplante de Rim , Mitocôndrias/metabolismo , Anticorpos/sangue , Cardiolipinas/metabolismo , Rejeição de Enxerto/etiologia , Humanos , Mitofagia , Estresse Oxidativo , Insuficiência Renal Crônica/terapia , Fatores de RiscoRESUMO
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.
RESUMO
Aminoguanidine (AG) inhibits advanced glycation end products (AGEs) and advanced oxidation protein products (AOPP) accumulated as a result of excessive oxidative stress in diabetes. However, the molecular mechanism by which AG reduces AGE-associated damage in diabetes is not well understood. Thus, we investigated whether AG supplementation mitigates oxidative-associated cardiac fibrosis in rats with type 2 diabetes mellitus (T2DM). Forty-five male Wistar rats were divided into three groups: Control, T2DM and T2DM+AG. Rats were fed with a high-fat, high-carbohydrate diet (HFCD) for 2 weeks and rendered diabetic using low-dose streptozotocin (STZ) (20 mg/kg), and one group was treated with AG (20 mg/kg) up to 25 weeks. In vitro experiments were performed in primary rat myofibroblasts to confirm the antioxidant and antifibrotic effects of AG and to determine if blocking the receptor for AGEs (RAGE) prevents the fibrogenic response in myofibroblasts. Diabetic rats exhibited an increase in cardiac fibrosis resulting from HFCD and STZ injections. By contrast, AG treatment significantly reduced cardiac fibrosis, α-smooth muscle actin (αSMA) and oxidative-associated Nox4 and Nos2 mRNA expression. In vitro challenge of myofibroblasts with AG under T2DM conditions reduced intra- and extracellular collagen type I expression and Pdgfb, Tgfß1 and Col1a1 mRNAs, albeit with similar expression of Tnfα and Il6 mRNAs. This was accompanied by reduced phosphorylation of ERK1/2 and SMAD2/3 but not of AKT1/2/3 and STAT pathways. RAGE blockade further attenuated collagen type I expression in AG-treated myofibroblasts. Thus, AG reduces oxidative stress-associated cardiac fibrosis by reducing pERK1/2, pSMAD2/3 and collagen type I expression via AGE/RAGE signaling in T2DM.
RESUMO
The therapeutic effects of telmisartan, an angiotensin II receptor antagonist and a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, have been demonstrated in several disorders. It has antioxidant and immune response modulator properties and has shown promising results in the treatment of an ischemia/reperfusion (I/R) lesion. In this study, a skeletal muscle (right gastrocnemius muscle) I/R lesion was induced in rats and different reperfusion times (1 h, 24 h, 72 h, 7-day, and 14-day subgroups) were assessed. Furthermore, levels of oxidative markers such as enzymatic scavengers (catalase (CAT) and superoxide dismutase (SOD)) and metabolites (nitrates and 8-oxo-deoxyguanosine) were determined. The degree of tissue injury (total lesioned fibers and inflammatory cell count) was also evaluated. We observed an increase in CAT and SOD expression levels under telmisartan treatment, with a decrease in injury and oxidative biomarker levels in the 72 h, 7-day, and 14-day subgroups. Telmisartan reduced oxidative stress and decreased the damage of the I/R lesion.
Assuntos
Anti-Hipertensivos/uso terapêutico , Isquemia/tratamento farmacológico , Telmisartan/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Humanos , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Traumatismo por Reperfusão , Telmisartan/farmacologiaRESUMO
Oxidative stress induces nerve damage in type 2 diabetes mellitus and leads to diabetic polyneuropathy (DPN) and can affect the DNA and antioxidant status. Statins have pleiotropic, protective effects on the peripheral nerves of patients with diabetes. The aim of this study was to determine the effects of ezetimibe/simvastatin and rosuvastatin on DNA damage in patients with DPN. This randomized, double-blind, placebo-controlled, clinical trial comprised outpatients from Guadalajara, Mexico. The inclusion criteria were either gender, age 35-80 years, type 2 diabetes, glycated hemoglobin ≤10%, diabetic polyneuropathy stage 1/2, and signed informed consent. Patients who were taking antioxidant therapy or statins, had hypersensitivity to drugs, experienced organ failure, were pregnant or breastfeeding, or had other types of neuropathy were excluded. We assigned patients to placebo, ezetimibe/simvastatin 10/20 mg, or rosuvastatin 20 mg, and the primary outcomes were 8-hydroxy-2'-deoxyguanosine (8-OHdG) for DNA damage, 8-oxoguanine-DNA-N-glycosilase (hOGG1) for DNA repair, and superoxide dismutase (SOD). Seventy-four patients were recruited. Nine patients were included as negative controls. There were no differences in 8-OHdG between the healthy subjects (4.68 [3.53-6.38] ng/mL) and the DPN patients (4.51 [1.22-9.84] ng/mL), whereas the hOGG1 level was 0.39 (0.37-0.42) ng/mL in the healthy subjects and 0.41 (0.38-0.54) ng/mL in patients with DPN at baseline (p = 0.01). SOD decreased significantly in patients with DPN (5.35 [0.01-17.90] U/mL) compared with the healthy subjects (9.81 [8.66-12.61] U/mL) at baseline (p < 0.001). No significant changes in DNA biomarkers were observed in any group between baseline and final levels. We noted a rise in hOGG1 in patients with DPN, without modifications after treatment. There was a slight, albeit insignificant, increase in SOD in patients who were on statins.