For years, there have been studies based on the use of natural compounds plant-derived as potential therapeutic agents for various diseases in humans. Curcumin is a phenolic compound extracted from ...Curcuma longa rhizome commonly used in Asia as a spice, pigment and additive. In traditional medicine of India and China, curcumin is considered as a therapeutic agent used in several foods. Numerous studies have shown that curcumin has broad biological functions particularly antioxidant and antiinflammatory. In fact, it has been established that curcumin is a bifunctional antioxidant; it exerts antioxidant activity in a direct and an indirect way by scavenging reactive oxygen species and inducing an antioxidant response, respectively. The renoprotective effect of curcumin has been evaluated in several experimental models including diabetic nephropathy, chronic renal failure, ischemia and reperfusion and nephrotoxicity induced by compounds such as gentamicin, adriamycin, chloroquine, iron nitrilotriacetate, sodium fluoride, hexavalent chromium and cisplatin. It has been shown recently in a model of chronic renal failure that curcumin exerts a therapeutic effect; in fact it reverts not only systemic alterations but also glomerular hemodynamic changes. Another recent finding shows that the renoprotective effect of curcumin is associated to preservation of function and redox balance of mitochondria. Taking together, these studies attribute the protective effect of curcumin in the kidney to the induction of the master regulator of antioxidant response nuclear factor erythroid-derived 2 (Nrf2), inhibition of mitochondrial dysfunction, attenuation of inflammatory response, preservation of antioxidant enzymes and prevention of oxidative stress. The information presented in this paper identifies curcumin as a promising renoprotective molecule against renal injury.
Cisplatin is widely used as chemotherapeutic agent for treatment of diverse types of cancer, however, acute kidney injury (AKI) is an important side effect of this treatment. Diverse mechanisms have ...been involved in cisplatin-induced AKI, such as oxidative stress, apoptosis and mitochondrial damage. On the other hand, curcumin is a polyphenol extracted from the rhizome of Curcuma longa L. Previous studies have shown that curcumin protects against the cisplatin-induced AKI; however, it is unknown whether curcumin can reduce alterations in mitochondrial bioenergetics and dynamic in this model. It was found that curcumin prevents cisplatin-induced: (a) AKI and (b) alterations in the following mitochondrial parameters: bioenergetics, ultrastructure, hydrogen peroxide production and dynamic. In fact, curcumin prevented the increase of mitochondrial fission 1 protein (FIS1), the decrease of optic atrophy 1 protein (OPA1) and the decrease of NAD+-dependent deacetylase sirtuin-3 (SIRT3), a mitochondrial dynamic regulator as well as the increase in the mitophagy associated proteins parkin and phosphatase and tensin homologue (PTEN)-induced putative kinase protein 1 (PINK1). In conclusion, the protective effect of curcumin in cisplatin-induced AKI was associated with the prevention of the alterations in mitochondrial bioenergetics, ultrastructure, redox balance, dynamic, and SIRT3 levels.
•Curcumin protects to mitochondrial bioenergetics alterations in cisplatin-induced AKI.•Curcumin decreases FIS1 protein levels and restore OPA1 protein levels in cisplatin-induced AKI.•Curcumin increases SIRT3 protein levels in cisplatin-induced AKI.
We previously reported that diabetes decreased the expression of renal tight junction (TJ) proteins claudin-5 in glomerulus, and claudin-2 and occludin in proximal tubule through an oxidative stress ...dependent way. Now we investigated whether all-trans retinoic acid (atRA), a compound that plays a relevant role in kidney maintenance and that possesses antioxidant properties, prevents loss of TJ proteins in streptozotocin (STZ)-treated rats. atRA was administered daily by gavage (1mg/kg) from Days 3–21 after STZ administration. atRA attenuated loss of body weight, proteinuria and natriuresis but it did not prevent hyperglucemia. Other metabolic alterations, such as: increased kidney injury molecule (KIM)-1, oxidative stress, protein kinase C (PKC) beta 2, NADPH oxidase subunits (p47phox and gp91phox) expressions and endothelial nitric oxide synthase (eNOS) uncoupling, and decreased nitric oxide synthesis, nuclear factor-erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions were also attenuated by atRA. In vitro scavenging capacity assays showed that atRA scavenged peroxyl radicals (ROO•), singlet oxygen (1O2) and hypochlorous acid (HOCl) in a concentration-dependent manner. Decreased expressions of occludin, claudins-2 and -5 induced by diabetes were ameliorated by atRA. We also found that diabetes induced tyrosine nitration (3-NT), SUMOylation and phosphorylation in serine residues of claudin-2 and atRA prevented these changes. In conclusion, atRA exerted nephroprotective effects by attenuating oxidative stress and preventing loss of renal TJ proteins.
Kidney is a target organ for heavy metals. They accumulate in several segments of the nephron and cause profound alterations in morphology and function. Acute intoxication frequently causes acute ...renal failure. The effects of chronic exposure have not been fully disclosed. In recent years increasing awareness of the consequences of their presence in the kidney has evolved. In this review we focus on the alterations induced by heavy metals on the intercellular junctions of the kidney. We describe that in addition to the proximal tubule, which has been recognized as the main site of accumulation and injury, other segments of the nephron, such as glomeruli, vessels, and distal nephron, show also deleterious effects. We also emphasize the participation of oxidative stress as a relevant component of the renal damage induced by heavy metals and the beneficial effect that some antioxidant drugs, such as vitamin A (all-trans-retinoic acid) and vitamin E (α-tocopherol), depict on the morphological and functional alterations induced by heavy metals.
We report the role of mitochondria in the protective effects of curcumin, a well-known direct and indirect antioxidant, against the renal oxidant damage induced by the hexavalent chromium Cr(VI) ...compound potassium dichromate (K2Cr2O7) in rats. Curcumin was given daily by gavage using three different schemes: (1) complete treatment (100, 200, and 400mg/kg bw 10days before and 2days after K2Cr2O7 injection), (2) pretreatment (400mg/kg bw for 10days before K2Cr2O7 injection), and (3) posttreatment (400mg/kg bw 2days after K2Cr2O7 injection). Rats were sacrificed 48h later after a single K2Cr2O7 injection (15mg/kg, sc) to evaluate renal and mitochondrial function and oxidant stress. Curcumin treatment (schemes 1 and 2) attenuated K2Cr2O7-induced renal dysfunction, histological damage, oxidant stress, and the decrease in antioxidant enzyme activity both in kidney tissue and in mitochondria. Curcumin pretreatment attenuated K2Cr2O7-induced mitochondrial dysfunction (alterations in oxygen consumption, ATP content, calcium retention, and mitochondrial membrane potential and decreased activity of complexes I, II, II–III, and V) but was unable to modify renal and mitochondrial Cr(VI) content or to chelate chromium. Curcumin posttreatment was unable to prevent K2Cr2O7-induced renal dysfunction. In further experiments performed in curcumin (400mg/kg)-pretreated rats it was found that this antioxidant accumulated in kidney and activated Nrf2 at the time when K2Cr2O7 was injected, suggesting that both direct and indirect antioxidant effects are involved in the protective effects of curcumin. These findings suggest that the preservation of mitochondrial function plays a key role in the protective effects of curcumin pretreatment against K2Cr2O7-induced renal oxidant damage.
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 (PKCβ2) and nicotinamide adenine dinucleotide phosphate oxidase subunits (p47phox and gp91phox) 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 PKCβ2, p47phox and gp91phox 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.
Renal complications in diabetes are severe and may lead to renal insufficiency. Early alterations in tight junction (TJ) proteins in diabetic nephropathy (DN) have not been explored and the role of ...oxidative stress in their disassembly has been poorly characterized. We investigated the expression and distribution of TJ proteins: claudin-5 in glomeruli (GL), occludin and claudin-2 in proximal tubules (PTs), and ZO-1 and claudin-1, -4, and -8 in distal tubules (DTs) of rats 21 days after streptozotocin injection. Redox status along the nephron segments was evaluated. Diabetes increased kidney injury molecule-1 expression. Expression of sodium glucose cotransporters (SGLT1 and SGLT2) and facilitative glucose transporter (GLUT2) was induced. Increased oxidative stress was present in GL and PTs and to a lesser extent in DTs (measured by superoxide production and PKCβ2 expression), owing to NADPH oxidase activation and uncoupling of the endothelial nitric oxide synthase-dependent pathway. Claudin-5, occludin, and claudin-2 expression was decreased, whereas claudin-4 and -8 expression increased. ZO-1 was redistributed from membrane to cytosol. Increased nitration of tyrosine residues in claudin-2 was found, which might contribute to decrement of this protein in proximal tubule. In contrast, occludin was not nitrated. We suggest that loss of claudin-2 is associated with increased natriuresis and that loss of glomerular claudin-5 might explain early presence of proteinuria. These findings suggest that oxidative stress is related to alterations in TJ proteins in the kidney that are relevant to the pathogenesis and progression of DN and for altered sodium regulation in diabetes.
•Superoxide anion production is increased in early development of diabetic nephropathy.•Diabetes causes disruption of renal tight junctions.•Renal claudin-2 nitration is present in the early stage of diabetes.•Glucose transporters are overexpressed in the initial establishment of diabetes.
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