RESUMO
Nephrotoxicity is an important adverse effect of oxidative stress induced by hexavalent chromium [Cr(VI)]. The effect of ellagic acid, a dietary polyphenolic compound with potent antioxidant activity, was investigated in Cr(VI)-induced kidney injury. Six groups of male Wistar rats were treated intragastrically with vehicle or ellagic acid (15 and 30 mg/kg) for 10 days. On day 10, rats received saline or Cr(VI) (K2Cr2O7 15 mg/kg) subcutaneously. Cr(VI) significantly increased kidney weight, affected kidney function assessed by biomarkers in blood and urine (protein, creatinine and urea nitrogen), caused histological changes (tubular injury and glomerular capillary tuft damage), increased markers of oxidative stress and reduced the activity of antioxidant enzymes. In addition, Cr(VI) altered mitochondrial ultrastructure, impaired mitochondrial respiration, increased lipid peroxidation, and inhibited the function of mitochondrial enzymes. Pretreatment with ellagic acid (30 mg/kg) attenuated all the aforementioned alterations. Furthermore, we explored whether ellagic acid might regulate the tumor necrosis factor-alpha (TNF-α)/receptor-interacting protein kinase 3 (RIPK3) pathway, reducing Cr(VI)-induced tubular necrosis. Cr(VI) upregulated both TNF-α and RIPK3, but ellagic acid only decreased TNF-α levels, having no effect on RIPK3 content. Therefore, understanding the mechanisms through which Cr(VI) promotes necroptosis is crucial for future studies, in order to design strategies to mitigate kidney damage. In conclusion, ellagic acid attenuated Cr(VI)-induced renal alterations by preventing oxidative stress, supporting enzymatic activities, suppressing TNF-α, and preserving mitochondrial ultrastructure and function, most likely due to its antioxidant properties.
Assuntos
Antioxidantes , Fator de Necrose Tumoral alfa , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Biomarcadores/metabolismo , Cromo/metabolismo , Cromo/toxicidade , Creatinina , Ácido Elágico/metabolismo , Ácido Elágico/farmacologia , Rim , Masculino , Mitocôndrias/metabolismo , Nitrogênio/metabolismo , Estresse Oxidativo , Proteínas Quinases/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/metabolismo , Ureia/metabolismoRESUMO
Mitochondria are the central target of ischemic preconditioning and postconditioning cardioprotective strategies, which consist of either the application of brief intermittent ischemia/reperfusion (I/R) cycles or the administration of pharmacological agents. Such strategies reduce cardiac I/R injury by activating protective signaling pathways that prevent the exacerbated production of reactive oxygen/nitrogen species, inhibit opening of mitochondrial permeability transition pore and reduce apoptosis, maintaining normal mitochondrial function. Cardioprotection also involves the activation of mitochondrial quality control (MQC) processes, which replace defective mitochondria or eliminate mitochondrial debris, preserving the structure and function of the network of these organelles, and consequently ensuring homeostasis and survival of cardiomyocytes. Such processes include mitochondrial biogenesis, fission, fusion, mitophagy and mitochondrial-controlled cell death. This review updates recent advances in MQC mechanisms that are activated in the protection conferred by different cardiac conditioning interventions. Furthermore, the role of extracellular vesicles in mitochondrial protection and turnover of these organelles will be discussed. It is concluded that modulation of MQC mechanisms and recognition of mitochondrial targets could provide a potential and selective therapeutic approach for I/R-induced mitochondrial dysfunction.
RESUMO
The cellular damage caused by redox imbalance is involved in the pathogenesis of many cardiovascular diseases. Besides, redox imbalance is related to the alteration of protein acetylation processes, causing not only chromatin remodeling but also disturbances in so many processes where protein acetylation is involved, such as metabolism and signal transduction. The modulation of acetylases and deacetylases enzymes aids in maintaining the redox homeostasis, avoiding the deleterious cellular effects associated with the dysregulation of protein acetylation. Of note, regulation of protein acetylation has shown protective effects to ameliorate cardiovascular diseases. For instance, HDAC inhibition has been related to inducing cardiac protective effects and it is an interesting approach to the management of cardiovascular diseases. On the other hand, the upregulation of SIRT protein activity has also been implicated in the relief of cardiovascular diseases. This review focuses on the major protein acetylation modulators described, involving pharmacological and bioactive compounds targeting deacetylase and acetylase enzymes contributing to heart protection through redox homeostasis.
Assuntos
Acetilação/efeitos dos fármacos , Doenças Cardiovasculares/enzimologia , Coração/fisiologia , Animais , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Histonas/metabolismo , Homeostase/efeitos dos fármacos , Humanos , Miocárdio/metabolismo , Oxirredução , Substâncias Protetoras/farmacologia , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ativação Transcricional/efeitos dos fármacosRESUMO
Lesions caused by high glucose (HG), hypoxia/reperfusion (H/R), and the coexistence of both conditions in cardiomyocytes are linked to an overproduction of reactive oxygen species (ROS), causing irreversible damage to macromolecules in the cardiomyocyte as well as its ultrastructure. Fenofibrate, a peroxisome proliferator-activated receptor alpha (PPARα) agonist, promotes beneficial activities counteracting cardiac injury. Therefore, the objective of this work was to determine the potential protective effect of fenofibrate in cardiomyocytes exposed to HG, H/R, and HG+H/R. Cardiomyocyte cultures were divided into four main groups: (1) control (CT), (2) HG (25 mM), (3) H/R, and (4) HG+H/R. Our results indicate that cell viability decreases in cardiomyocytes undergoing HG, H/R, and both conditions, while fenofibrate improves cell viability in every case. Fenofibrate also decreases ROS production as well as nicotinamide adenine dinucleotide phosphate oxidase (NADPH) subunit expression. Regarding the antioxidant defense, superoxide dismutase (SOD Cu2+/Zn2+ and SOD Mn2+), catalase, and the antioxidant capacity were decreased in HG, H/R, and HG+H/R-exposed cardiomyocytes, while fenofibrate increased those parameters. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) increased significantly in treated cells, while pathologies increased the expression of its inhibitor Keap1. Oxidative stress-induced mitochondrial damage was lower in fenofibrate-exposed cardiomyocytes. Endothelial nitric oxide synthase was also favored in cardiomyocytes treated with fenofibrate. Our results suggest that fenofibrate preserves the antioxidant status and the ultrastructure in cardiomyocytes undergoing HG, H/R, and HG+H/R preventing damage to essential macromolecules involved in the proper functioning of the cardiomyocyte.
RESUMO
[This corrects the article DOI: 10.1155/2016/7367641.].
RESUMO
The nuclear factor-erythroid 2- (NF-E2-) related factor 2 (Nrf2) is abated and its ability to reduce oxidative stress is impaired in type 2 diabetes and obesity. Thus, the aim of this study was to explore if polymorphisms in Nrf2 and target genes are associated with diabetes and obesity in Mexican mestizo subjects. The rs1800566 of NAD(P)H: quinone oxidoreductase 1 (NQO1) gene, rs7211 of thioredoxin interacting protein (TXNIP) gene, rs2071749 of heme oxygenase-1 (HMOX1) gene, and the rs6721961 and the rs2364723 from Nrf2 gene were genotyped in 627 diabetic subjects and 1020 controls. The results showed that the rs7211 polymorphism is a protective factor against obesity in nondiabetic subjects (CC + CT versus TT, OR = 0.40, P = 0.005) and in women (CC versus CT + TT, OR = 0.7, P = 0.016). TT carriers had lower high-density lipoprotein cholesterol levels and lower body mass index. The rs2071749 was positively associated with obesity (AA versus AG + GG, OR = 1.25, P = 0.026). Finally, the rs6721961 was negatively associated with diabetes in men (CC versus CA + AA, OR = 0.62, P = 0.003). AA carriers showed lower glucose concentrations. No association was found for rs1800566 and rs2364723 polymorphisms. In conclusion, the presence of Nrf2 and related genes polymorphisms are associated with diabetes and obesity in Mexican patients.
Assuntos
Proteínas de Transporte/genética , Diabetes Mellitus/genética , Heme Oxigenase-1/genética , Fator 2 Relacionado a NF-E2/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adulto , Biomarcadores/sangue , Glicemia/análise , Índice de Massa Corporal , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/enzimologia , Diabetes Mellitus/etnologia , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Hemoglobinas Glicadas/análise , Humanos , Lipídeos/sangue , Modelos Logísticos , Masculino , México , Pessoa de Meia-Idade , Análise Multivariada , NAD(P)H Desidrogenase (Quinona)/genética , Obesidade/diagnóstico , Obesidade/enzimologia , Obesidade/etnologia , Razão de Chances , Estresse Oxidativo/genética , Fenótipo , Fatores de Proteção , Fatores de Risco , Fatores SexuaisRESUMO
OBJECTIVE: Chronic kidney disease (CKD) is a worldwide public health problem, and proteinuria may accelerate the progression of CKD, being oxidative stress a common mechanism in nondiabetic or diabetic proteinuric kidney disease. This study was designed to evaluate the effect of the dietary supplementation with curcumin (CUR) on the redox status and the nuclear factor erythroid 2-related factor 2 (Nrf2) activation in patients with nondiabetic or diabetic proteinuric CKD. DESIGN: Randomized double-blind placebo-controlled clinical trial. SUBJECTS: A total of 101 Mexican patients from the National Institute of Cardiology "Ignacio Chavez", with nondiabetic or diabetic proteinuric CKD (proteinuria ≥ 1 g protein/24 hours), aged 20 to 70 years; 60% were male, and 51% were diabetic. INTERVENTION: Patients with nondiabetic proteinuric CKD received placebo (n = 26) or CUR 320 mg/day (n = 24) for 8 weeks, and patients with diabetic proteinuric CKD were intervened with placebo (n = 23) or CUR 320 mg/day (n = 28) for the same period. MAIN OUTCOME MEASURE: Anthropometrical, clinical, and biochemical characteristics, as well as oxidative stress markers, antioxidant enzyme activities and Nrf2 activation were evaluated at baseline and after intervention. RESULTS: The intervention with CUR did not improve proteinuria, estimated glomerular filtration rate, or lipid profile. However, in plasma, CUR attenuated lipid peroxidation in individuals with nondiabetic proteinuric CKD (P<.05) and enhanced the antioxidant capacity in subjects with diabetic proteinuric CKD (P<.05). No effect of CUR was observed on the antioxidant enzymes activities or Nrf2 activation. CONCLUSIONS: Dietary supplementation with CUR has the potential to reduce oxidative stress in Mexican patients with nondiabetic or diabetic proteinuric CKD. Studies with higher doses of CUR and longer follow-up are granted to confirm our findings.
Assuntos
Curcumina/administração & dosagem , Nefropatias Diabéticas/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Oxirredução/efeitos dos fármacos , Proteinúria/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Idoso , Índice de Massa Corporal , Curcuma/química , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , México , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Adulto JovemRESUMO
It has been shown that curcumin (CUR), a polyphenol derived from Curcuma longa, exerts a protective effect against gentamicin- (GM-) induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2)-related factor 2 (Nrf2) nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) cell expression attenuating GM-induced losses in these proteins. In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h) during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day) was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.
RESUMO
Hexavalent chromium [Cr(VI)] compounds are extremely toxic and carcinogenic. Despite the vast quantity of reports about Cr(VI) toxicity, the information regarding its effects when it is intraperitoneally (i.p.) administered is still limited. In contrast, it has been shown that curcumin prevents hepatotoxicity induced by a single intraperitoneal injection of 15 mg/kg body weight (b.w.) of potassium dichromate (K2Cr2O7). This study aims to evaluate oxidative stress markers, the activity of antioxidant enzymes, and the potential histological injury in brain, heart, lung, kidney, spleen, pancreas, stomach, and intestine from rats treated with a hepatotoxic dose of K2Cr2O7 (15 mg/kg b.w.), and the effect of curcumin pretreatment. Rats were divided into four groups: control, curcumin, K2Cr2O7, and curcumin+K2Cr2O7. At the end of the treatment, plasma and ascites fluid were collected and target organs were dissected out for biochemical and histological analysis. K2Cr2O7 induced hepatotoxicity but failed to induce in all the other studied organs either oxidative or histological injury, since levels of malondialdehyde (MDA), glutathione (GSH), and the activity of superoxide dismutase (SOD), catalase (CAT), and related GSH enzymes were unchanged. As expected, curcumin was safe. Lack of K2Cr2O7-induced toxicity in those target organs could be due to the following: (1) route of administration, (2) absorption through the portal circulation, (3) lower dose than needed, (4) short time of exposure, or (5) repeated doses are required to produce damage. Thus, the intraperitoneal injection of 15 mg/kg of K2Cr2O7, that is able to induce hepatotoxicity, was unable to induce histological and oxidative damage in other target organs.
Assuntos
Biomarcadores/metabolismo , Curcumina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Dicromato de Potássio/toxicidade , Análise de Variância , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Catalase/metabolismo , Relação Dose-Resposta a Droga , Mucosa Gástrica/metabolismo , Injeções Intraperitoneais , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Malondialdeído/sangue , Malondialdeído/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , Tamanho do Órgão/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Pâncreas/metabolismo , Pâncreas/patologia , Dicromato de Potássio/administração & dosagem , Ratos Wistar , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Estômago/efeitos dos fármacos , Estômago/patologia , Superóxido Dismutase/metabolismoRESUMO
Occupational and environmental exposure to potassium dichromate (K2Cr2O7), a hexavalent chromium compound, can result in liver damage associated with oxidative stress and mitochondrial dysfunction. The purpose of this study was to evaluate the effect of the antioxidant curcumin (400 mg/kg b.w.) on the K2Cr2O7-induced injury, with special emphasis on ascitic fluid accumulation and oxidative phosphorylation mitochondrial enzymes and the adenosine triphosphate (ATP) levels in isolated mitochondria from livers of rats treated with K2Cr2O7 (15 mg/kg b.w.). Thus, curcumin attenuated the ascites generation, prevented the decrease in the activities of aconitase and F1F0 ATPase, and maintained the ATP levels. The activity of complex II was not completely reestablished by curcumin, whereas complexes III and IV activities were unchanged.
Assuntos
Ascite/prevenção & controle , Curcumina/uso terapêutico , Mitocôndrias Hepáticas/efeitos dos fármacos , Dicromato de Potássio/toxicidade , Aconitato Hidratase/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Ascite/induzido quimicamente , Ascite/metabolismo , Líquido Ascítico/fisiologia , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Mitocôndrias Hepáticas/enzimologia , Mitocôndrias Hepáticas/metabolismo , Estresse Oxidativo/fisiologia , ATPases Translocadoras de Prótons/metabolismo , Ratos , Ratos WistarRESUMO
OBJECTIVES: Cisplatin (CP) is an antineoplastic agent that induces nephrotoxicity and oxidative stress. S-allylcysteine (SAC) is a garlic-derived antioxidant. This study aims to explore whether SAC protects against CP-induced nephrotoxicity in rats. METHODS: In the first stage, the SAC protective dose was determined by measuring renal damage and the oxidative stress markers malondialdehyde, oxidized proteins and glutathione in rats injected with CP. In the second stage, the effect of a single dose of SAC on the expression of nuclear factor-erythroid 2-related factor-2 (Nrf2), protein kinase C beta 2 (PKCß2) and nicotinamide adenine dinucleotide phosphate oxidase subunits (p47(phox) and gp91(phox) ) was studied. In addition, the effect of SAC on oxidative stress markers and on the activity of catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) in isolated proximal and distal tubules were evaluated. KEY FINDINGS: SAC (25 mg/kg) prevented the CP-induced renal damage and attenuated CP-induced decrease in Nrf2 levels and increase in PKCß2, p47(phox) and gp91(phox) expression in renal cortex and oxidative stress and decrease in the activity of CAT, GPx and GR in proximal and distal tubules. CONCLUSIONS: These data suggest that SAC provides renoprotection by attenuating CP-induced oxidative stress and decrease in the activity of CAT, GPx and GR.
Assuntos
Antioxidantes/uso terapêutico , Cisplatino/efeitos adversos , Cisteína/análogos & derivados , Alho/química , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Antineoplásicos/efeitos adversos , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Catalase/metabolismo , Cisplatino/uso terapêutico , Cisteína/farmacologia , Cisteína/uso terapêutico , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Rim/metabolismo , Nefropatias/metabolismo , Masculino , Malondialdeído/metabolismo , Glicoproteínas de Membrana/metabolismo , NADPH Oxidase 2 , NADPH Oxidases/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Proteína Quinase C beta/metabolismo , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Occupational or environmental exposures to heavy metals produce several adverse health effects. The common mechanism determining their toxicity and carcinogenicity is the generation of oxidative stress that leads to hepatic damage. In addition, oxidative stress induced by metal exposure leads to the activation of the nuclear factor (erythroid-derived 2)-like 2/Kelch-like ECH-associated protein 1/antioxidant response elements (Nrf2/Keap1/ARE) pathway. Since antioxidant and chelating agents are generally used for the treatment of heavy metals poisoning, this review is focused on the protective role of curcumin against liver injury induced by heavy metals. Curcumin has shown, in clinical and preclinical studies, numerous biological activities including therapeutic efficacy against various human diseases and anti-hepatotoxic effects against environmental or occupational toxins. Curcumin reduces the hepatotoxicity induced by arsenic, cadmium, chromium, copper, lead and mercury, prevents histological injury, lipid peroxidation and glutathione (GSH) depletion, maintains the liver antioxidant enzyme status and protects against mitochondrial dysfunction. The preventive effect of curcumin on the noxious effects induced by heavy metals has been attributed to its scavenging and chelating properties, and/or to the ability to induce the Nrf2/Keap1/ARE pathway. However, additional research is needed in order to propose curcumin as a potential protective agent against liver damage induced by heavy metals.
Assuntos
Curcumina/farmacologia , Fígado/efeitos dos fármacos , Metais Pesados/toxicidade , Substâncias Protetoras/farmacologia , Animais , Arsênio/toxicidade , Cádmio/toxicidade , Cobre/toxicidade , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch , Chumbo/toxicidade , Fígado/metabolismo , Fígado/patologia , Mercúrio/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
Curcumin is a polyphenol derived from turmeric with recognized antioxidant properties. Hexavalent chromium is an environmental toxic and carcinogen compound that induces oxidative stress. The objective of this study was to evaluate the potential protective effect of curcumin on the hepatic damage generated by potassium dichromate (K2Cr2O7) in rats. Animals were pretreated daily by 9-10 days with curcumin (400 mg/kg b.w.) before the injection of a single intraperitoneal of K2Cr2O7 (15 mg/kg b.w.). Groups of animals were sacrificed 24 and 48 h later. K2Cr2O7-induced damage to the liver was evident by histological alterations and increase in the liver weight and in the activity of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and alkaline phosphatase in plasma. In addition, K2Cr2O7 induced oxidative damage in liver and isolated mitochondria, which was evident by the increase in the content of malondialdehyde and protein carbonyl and decrease in the glutathione content and in the activity of several antioxidant enzymes. Moreover, K2Cr2O7 induced decrease in mitochondrial oxygen consumption, in the activity of respiratory complex I, and permeability transition pore opening. All the above-mentioned alterations were prevented by curcumin pretreatment. The beneficial effects of curcumin against K2Cr2O7-induced liver oxidative damage were associated with prevention of mitochondrial dysfunction.
RESUMO
Renal injury resulting from renal ablation induced by 5/6 nephrectomy (5/6NX) is associated with oxidant stress, glomerular hypertension, hyperfiltration, and impaired Nrf2-Keap1 pathway. The purpose of this work was to know if the bifunctional antioxidant curcumin may induce nuclear translocation of Nrf2 and prevents 5/6NX-induced oxidant stress, renal injury, decrease in antioxidant enzymes, and glomerular hypertension and hyperfiltration. Four groups of rats were studied: (1) control, (2) 5/6NX, (3) 5/6NX +CUR, and (4) CUR (n = 8-10). Curcumin was given by gavage to NX5/6 +CUR and CUR groups (60 mg/kg/day) starting seven days before surgery. Rats were studied 30 days after NX5/6 or sham surgery. Curcumin attenuated 5/6NX-induced proteinuria, systemic and glomerular hypertension, hyperfiltration, glomerular sclerosis, interstitial fibrosis, interstitial inflammation, and increase in plasma creatinine and blood urea nitrogen. This protective effect was associated with enhanced nuclear translocation of Nrf2 and with prevention of 5/6NX-induced oxidant stress and decrease in the activity of antioxidant enzymes. It is concluded that the protective effect of curcumin against 5/6NX-induced glomerular and systemic hypertension, hyperfiltration, renal dysfunction, and renal injury was associated with the nuclear translocation of Nrf2 and the prevention of both oxidant stress and the decrease of antioxidant enzymes.