Oxidative Stress In Renal Cells Research Articles

Abnormal Lipoproteins Trigger Oxidative Stress-Mediated Apoptosis of Renal Cells in LCAT Deficiency.

Familial lecithin:cholesterol acyltransferase (LCAT) deficiency (FLD) is a rare genetic disease caused by the loss of function mutations in the LCAT gene. LCAT deficiency is characterized by an abnormal lipoprotein profile with severe reduction in plasma levels of high-density lipoprotein (HDL) cholesterol and the accumulation of lipoprotein X (LpX). Renal failure is the major cause of morbidity and mortality in FLD patients; the pathogenesis of renal disease is only partly understood, but abnormalities in the lipoprotein profile could play a role in disease onset and progression. Serum and lipoprotein fractions from LCAT deficient carriers and controls were tested for renal toxicity on podocytes and tubular cells, and the underlying mechanisms were investigated at the cellular level. Both LpX and HDL from LCAT-deficient carriers triggered oxidative stress in renal cells, which culminated in cell apoptosis. These effects are partly explained by lipoprotein enrichment in unesterified cholesterol and ceramides, especially in the HDL fraction. Thus, alterations in lipoprotein composition could explain some of the nephrotoxic effects of LCAT deficient lipoproteins on podocytes and tubular cells.

Protective Effects of Total Flavonoids from Lysimachia christinae on Calcium Oxalate-Induced Oxidative Stress in a Renal Cell Line and Renal Tissue.

Oxidative stress (OS) in renal tubular epithelial cells (RTECs) is induced by calcium oxalate (CaOx) stones and plays an important role in the pathology of CaOx nephrolithiasis. The nuclear factor-E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important endogenous antioxidant pathway. Flavonoids are compounds with 2-phenylchromone as the basic mother nucleus and are natural antioxidant components of Lysimachia christinae. Our previous studies demonstrated that the total flavonoids from L. christinae (TFL) reduced calcium and oxalic acid concentrations in urine, thus inhibiting CaOx stone formation. We also showed that TFL can reduce OS in renal tissue. However, whether TFL inhibit the formation of CaOx stones through the Nrf2/ARE pathway requires further investigation. Here, we found that TFL protected against injury to a renal cell line and renal tissue, reduced CaOx-induced OS in renal tissue, and reduced CaOx crystal formation. In addition, TFL significantly increased nuclear Nrf2 and the expression of the downstream antioxidant genes heme oxygenase 1 (HO-1) and NAD(P)H quinone oxidoreductase 1 (NQO-1). Furthermore, TFL increased superoxide dismutase (SOD) activity and decreased the malondialdehyde (MDA) content, thereby alleviating OS in RTECs. Silencing Nrf2 expression blocked the protective effect of TFL on CaOx-induced OS. Taken together, our findings indicate that TFL reduce CaOx-induced OS in renal tissue by activating the Nrf2/ARE pathway.

In vitro toxicological evaluation of arsenic on superoxide dismutase mediated oxidative stress in renal cells of rat and its amelioration with supplementation of Pleurotus florida lectin (PFL)

Concomitant oral supplementation of Pleurotus florida lectin (PFL) (@50μg/ml) on arsenic (@ 5 μM) exposed renal cells was investigated to evaluate the protective value of PFL against arsenic toxicity in rats. Renal cells, exposed to arsenic(III), showed a significant inhibition of cell proliferation index (CPI) and superoxide dismutase (SOD) acid and catalase (CAT) activity with an increased level of lipid peroxidation (LPO). A marginally increased level of nitric oxide (NO) was found firstly and thereafter decreased due to long-term arsenic exposure in the cells. Concurrent application of PFL in arsenic exposed renal cells had remarkable protective effect on inhibited CPI, SOD, and CAT activity and restored LPO and NO level in renal cells. Arsenic caused down-regulation of mRNA expression of SOD2 gene that was reversed by administration of PFL. The results concluded that supplementation of PFL protected renal cells against arsenic-induced oxidative stress.

Metabolic syndrome during gestation and lactation: An important renal problem in dams. selenium renal clearance

BackgroundMetabolic syndrome (MS) in lactating dams leads to several cardiometabolic changes related to selenium (Se) status and selenoproteins expression which produce hypertension. However, little is known about the state of these dams’ kidney functions and their Se deposits. MethodsTwo experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65 % and Se: 0.1 ppm). At the end of lactation (21d postpartum) kidney weight and protein content, Se deposits, and the activity of the antioxidant selenoprotein glutathione peroxidase (GPx) were measured in dams. Kidney functional parameters: albuminuria, creatinine clearance, serum aldosterone and uric acid levels and water and electrolyte (Na+ and K+) balance were also evaluated. Systolic blood pressure (SBP) was measured. ResultsIn MS dams at the end of lactation Se deposits and GPx activity are higher in the kidney; however, lipid renal peroxidation appears, relative Se clearance increases, and the dams have lost Se by urine. MS dams have polyuria and polydipsia, high uric acid serum levels, albuminuria and high creatinine clearance, implying glomerular renal malfunction with protein loss. They also present hypernatremia, hypokalemia and hyperaldosteronemia, leading to high SBP; however, a natriuretic process is taking place. ConclusionSince these alterations appear, at least in part, to be related to oxidative stress in renal cells, Se supplementation could be beneficial to avoiding greater lipid renal oxidation during lactation.

Vitamin E (α‑tocopherol) ameliorates aristolochic acid‑induced renal tubular epithelial cell death by attenuating oxidative stress and caspase‑3 activation.

Aristolochic acid (AA) is a component identified in traditional Chinese remedies for the treatment of arthritic pain, coughs and gastrointestinal symptoms. However, previous studies have indicated that AA can induce oxidative stress in renal cells leading to nephropathy. α-tocopherol exists in numerous types of food, such as nuts, and belongs to the vitamin E isoform family. It possesses antioxidant activities and has been used previously for clinical applications. Therefore, the aim of the present study was to determine whether α-tocopherol could reduce AA-induced oxidative stress and renal cell cytotoxicity, determined by cell survival rate, reactive oxygen species detection and apoptotic features. The results indicated that AA markedly induced H2O2 levels and caspase-3 activity in renal tubular epithelial cells. Notably, the presence of α-tocopherol inhibited AA-induced H2O2 and caspase-3 activity. The present study demonstrated that antioxidant mechanisms of α-tocopherol may be involved in the increased survival rates from AA-induced cell injury.

Renoprotective Effects of 4‐Phenylbutyrate Against Palmitate‐Induced Renal Cell Injury

BackgroundIncreased dietary intake of fats rich in saturated fatty acids and dyslipidemia have been shown to significantly aggravate the risk of cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Although multiple mechanisms including endoplasmic reticulum (ER) stress and oxidative stress are implicated in the pathophysiology of CKD, the effects of elevated free fatty acid (FFA) levels per se on renal cells is still unclear. Hence, we investigated the effects of palmitic acid (a saturated fatty acid) on rat renal proximal tubular cells in vitro, and tested the renoprotective effects of 4‐phenylbutyrate (4‐PBA), a chemical chaperone shown to inhibit ER stress in vitro and in vivo, in our model.MethodsSubconfluent rat renal proximal tubular (NRK‐52E) cells were exposed to 100 mM palmitic acid in presence and absence of 5 mM 4‐PBA for 24 hours. Cells were then assessed for alterations in cell viability (using MTT assay), oxidative stress (via Dichlorofluorescein (DCF) staining) and the expression of ER stress markers (i.e., glucose‐regulated protein, GRP78 and C/EBP homologous protein, CHOP) and apoptosis (caspase‐3 and ‐12) using western blotting. Flow cytometry for cell cycle analysis and immunoblotting for p27 (an inhibitor of cell cycle) were performed to determine the effects of palmitate and 4‐PBA on the cell cycle in renal cells.ResultsRenal cells exposed to palmitate for 24 hours showed decreased viability (76.9% to that of control), increased DCF staining (1.3‐fold increase over control), and marked upregulation of GRP78 and CHOP. Similarly, the expression of active forms of caspase‐3 (1.8‐fold increase over control) and caspase‐12 (3‐fold increase over control) were also increased in renal cells treated with palmitate. These changes were significantly attenuated in cells co‐treated with 4‐PBA. Intriguingly, exposure to palmitate did not alter the cell cycle in renal cells, whereas treatment with 4‐PBA caused downregulation of p27 (54% to that of control) and increased the transition of cells from G1 to S‐phase and G2/M phase.ConclusionsOur findings indicate that exposure to palmitate induces ER stress as well as oxidative stress in renal cells, and results in renal cell apoptosis. Co‐treatment with 4‐PBA protects renal cells against the perturbations induced by palmitate and improves renal cell viability, which underscores the renoprotective effects of 4‐PBA against fatty acid‐induced renal cell injury. Further studies are required to understand the mechanisms by which 4‐PBA prevents oxidative stress and alters cell cycle in renal cells.Support or Funding InformationSupported by student research grants # QUST‐CPH‐FALL‐12/13‐6 and QUST‐CPH‐SPR‐12/13‐3 from the Office of Academic Research, Qatar University.

Effects of PACAP on Oxidative Stress-Induced Cell Death in Rat Kidney and Human Hepatocyte Cells

Oxidative stress plays an important role in various renal and hepatic pathologies, and reduction of oxidative stress-induced processes is an important protective strategy in tissues of diverse origins against harmful stimuli. Pituitary adenylate cyclase activating polypeptide (PACAP) is a well-known cytotrophic and cytoprotective peptide. PACAP promotes cell survival in numerous cells and tissues exposed to various stimuli. Protective effects of PACAP have been shown in the kidney, but it is not known whether PACAP is protective against oxidative stress in renal cells. Little is known about the effects of PACAP in the liver. The aim of the present study was to investigate whether PACAP is protective against oxidative stress in primary rat kidney cell culture and whether PACAP has any effect on cell survival in human WRL-68 hepatocytes and HEP-G2 hepatocellular carcinoma cells subjected to oxidative stress. Cells were exposed to various concentrations of H(2)O(2) with or without PACAP co-treatment and cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide test (MTT). We found that oxidative stress induced a significant decrease in cell viability in both cell lines. PACAP could dose-dependently increase the percentage of living cells in kidney cells, but it failed to do so in hepatocytes. Given the survival-promoting effects of PACAP against oxidative stress in rat kidney, we conducted a further experiment to determine whether PACAP influences the markers of oxidative stress in vivo. We have proven earlier that PACAP was effective in kidney ischemia/reperfusion injury in vivo. In the present study, we determined the levels of the oxidative stress marker malondialdehyde and the activity of the scavenger molecules glutathione (GSH) and superoxide dismutase (SOD) following kidney ischemia/reperfusion in rats. We found that PACAP significantly increased the level of GSH and counteracted the marked reduction of SOD activity after ischemia/reperfusion in vivo. In summary, the present study showed that while PACAP was able to significantly increase the cell survival in primary kidney cell cultures exposed to oxidative stress, possibly involving interaction with the endogenous scavenger system, it failed to influence the viability of normal or cancerous hepatocytes.