• Korean Journal of Fisheries and Aquatic Sciences
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• v.38 no.5
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• pp.304-308
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• 2005

The effects of diethylhexyl phthalate (DEHP) on various oxidative stress responses in liver, kidney and gill tissues of freshwater bagrid catfish Pseudobagrus fulvidraco were investigated under laboratory conditions. Bagrid catfish were intraperitoneally injected with sunflower seed oil containing nominal concentrations of 0, 300 or 900mg DEHP per kilogram of body weight for 3 days and the effects after last injection were assessed in liver, kidney and gill tissues of the exposed organisms. The oxidative stress responses of fish were evaluated by analyzing the level of glutathione (GSH), as well as the activities of antioxidant enzymes such as glutathione S-transferase (GST), glutathione peroxidase (GPx) and glutathione reductase (GR). After exposure to the DEHP, there were significant decrease in GR, GPx activity and GSH content in liver of fish exposed to 900 mg DEHP per kilogram of body weight compared to the control group. Compared with the control group, significant decreases in renal GPx and GR activity were observed in the DEHP treatment groups (900 mg $kg^{-1}$ bw). However, no significant difference was observed in any oxidative stress responses in gills between the DEHP-treated and the untreated group of fish. The findings of the present investigation show that DEHP induce oxidative stress and the liver was the most affected organ followed by the kidney and gills. Furthermore, the changes of GPx and GR activities may be important indicators of oxidative stress responses but additional study is required to confirm the oxidative stress of DEHP.

• Biomolecules & Therapeutics
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• v.28 no.1
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• pp.25-33
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• 2020

Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H₂O₂), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptor-mediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.

• Preventive Nutrition and Food Science
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• v.21 no.4
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• pp.378-383
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• 2016

Diabetic kidney disease is the most common and severe chronic complication of diabetes. The leaf of Diospyros kaki Thumb (persimmon) has been commonly used for herbal tea and medicinal purposes to treat a variety of conditions, including hypertension and atherosclerosis. However, the effect of persimmon leaf on kidney failure has not been investigated. This study aimed to examine the role of persimmon leaf in protecting the diabetes-associated kidney damage in a mouse model of type 2 diabetes. Mice were fed either a normal chow diet with or without powered persimmon leaf (5%, w/w) for 5 weeks. In addition to kidney morphology and blood markers of kidney function, we assessed levels of oxidative stress markers as well as antioxidant enzymes activities and mRNA expression in the kidney. Supplementation of the diet with powered persimmon leaf not only decreased the concentration of blood urea nitrogen in the plasma but also improved glomerular hypertrophy. Furthermore, the persimmon leaf significantly decreased the levels of hydrogen peroxide and lipid peroxide in the kidney. The activities of superoxide dismutase, catalase, and glutathione peroxidase and the mRNA expression of their respective genes were also increased in the kidney of persimmon leaf-supplemented db/db mice. Taken together, these results suggest that supplementation with the persimmon leaf may have protective effects against type 2 diabetes-induced kidney dysfunction and oxidative stress.

• Nutrition Research and Practice
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• v.8 no.1
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• pp.46-53
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• 2014

Inorganic arsenic (iAs) is a toxic metalloid found ubiquitously in the environment. In humans, exposure to iAs can result in toxicity and cause toxicological manifestations. Arsenic trioxide ($As_2O_3$) has been used in the treatment for acute promyelocytic leukemia. The kidney is the critical target organ of trivalent inorganic As ($iAs^{III}$) toxicity. We examine if oral administration of astaxanthin (AST) has protective effects on nephrotoxicity and oxidative stress induced by $As_2O_3$ exposure (via intraperitoneal injection) in rats. Markers of renal function, histopathological changes, $Na^+-K^+$ ATPase, sulfydryl, oxidative stress, and As accumulation in kidneys were evaluated as indicators of $As_2O_3$ exposure. AST showed a significant protective effect against $As_2O_3$-induced nephrotoxicity. These results suggest that the mechanisms of action, by which AST reduces nephrotoxicity, may include antioxidant protection against oxidative injury and reduction of As accumulation. These findings might be of therapeutic benefit in humans or animals suffering from exposure to $iAs^{III}$ from natural sources or cancer therapy.

• Preventive Nutrition and Food Science
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• v.13 no.2
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• pp.84-89
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• 2008

This study was designed to investigate the protective effect of a methanol extract of Chungkookjang (CKJ) on high glucose induced oxidative stress in LLC-$PK_1$ cells (renal tubular epithelial cells), which are susceptible to oxidative stress. Freeze dried CKJ powder was extracted with methanol, and the extract solution was concentrated, and then used in this study. To determine the protective effect of CKJ extract, oxidative stress was induced by exposing of LLC-$PK_1$ cells to high glucose (30 mM) or normal glucose (5 mM) for 24 hr. Exposure of LLC-$PK_1$ cells to high glucose for 24 hr resulted in a significant (p<0.05) decrease in cell viability, catalase, SOD and GSH-px activity and a significant (p<0.05) increase in intracellular ROS level and thiobarbituric acid reactive substances (TBARS) formation in comparison to the cells treated with 5 mM glucose. CKJ extract treatment decreased intracellular ROS level and TBARS formation, and increased cell viability and activities of antioxidant enzymes including catalase, SOD and GSH-px in high glucose pretreated LLC-$PK_1$ cells. These results suggest that CKJ extract may be able to protect LLC-$PK_1$ cells from high glucose-induced oxidative stress, partially through the antioxidative defense systems.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.95-102
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• 1995

The pathogenesis of diabetic nephropathy is still not completely understood while renal disease is one of the most common disabling complications of diabetes. We, in the present study, investigated the possible involvement of oxidative stress in the development of diabetic nephropathy. To hasten the development of diabetic nephropathy, streptozotocin was injected to unilaterally nephrectomized rats (NEPH-STZ). Eight weeks later, NEPH-STZ rats developed severe hyperglycemia, proteinuria, and hypertension. The kidneys of these rats showed compensatory hypertrophy and mesangial expansion. In contrast, the rats with streptozotocin injection alone (STZ) did not increase urinary protein excretion. Nephrectomized non-diabetic rats (NEPH) developed increased urine protein excretion, but without prominent renal morphological changes. However, oxidation of renal cortical tissue protein significantly increased in all 3 groups of NEPH, STZ and NEPH-STZ in comparison to control rats (CONT). The result indicates the non-specificity of the oxidative tissue damage and suggests that the oxidative damage is hardly a sole mechanism leading to the development of the diabetic nephropathy. However, it would still be a contributing factor considering that the oxidative stress is a common final pathway mediating tissue damages in chronic diabetic complications and other serious illness.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.8
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• pp.303-312
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• 2019

Oxidative stress in kidneys can precede the development of chronic renal injury. We investigated the antioxidative effect of membrane-free stem cell extract (MFSCE) from adipose tissue in LLC-$PK_1$ renal proximal tubule cells. Treatment of LLC-$PK_1$ cells with MFSCE showed the up-regulation of heme-oxygenase-1, thioredoxin reductase 1, and NADPH quinine oxidoreductase-1 protein expressions, which are proteins related with antioxidative activities. When oxidative stress was induced by 3-morpholinosydnonimine (SIN-1), cell viability was decreased, indicating that LLC-$PK_1$ cells were damaged by SIN-1. However, MFSCE significantly elevated cell viability from 58.84% to 64.43% at the concentration of $2.5{\mu}g/mL$ in oxidative stress-induced LLC-$PK_1$ cells. Furthermore, MFSCE ameliorated inflammation and apoptosis in SIN-1-treated LLC-$PK_1$ cells by modulating protein expressions. Inducible nitric oxide synthase and cyclooxygenase-2 protein expressions were down-regulated when LLC-$PK_1$ cells were treated with MFSCE. Apoptosis-related proteins, including B-cell lymphoma-2-associated X protein/B-cell lymphoma-2 ratio, cleaved caspase-3, and cleaved-poly (ADP-ribose) polymerase, were also down-regulated. It indicated that MFSCE protected apoptosis against oxidative stress in LLC-$PK_1$ cells. Taken together, these results suggested that MFSCE had a protective effect against SIN-1-induced oxidative stress in LLC-$PK_1$ cells. Therefore, MFSCE could be a promising therapeutic agent for oxidative stress-induced renal injury.

• Journal of Marine Bioscience and Biotechnology
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• v.13 no.2
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• pp.94-103
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• 2021

Here, we evaluated the anti-glycation effects and renal protective properties of 70% (v/v) ethanolic extract of Colpomenia sinuosa (CSE) against AGEs -induced oxidative stress and apoptosis at different concentrations (1, 5, and 20 ㎍/mL). At 20 ㎍/mL, CSE showed that anti-glycation activities via the inhibition of AGE formation (51.1%), inhibition of AGEs-protein cross-linking (61.7%), and breaking of AGEs-protein cross-links (33.3%), were significantly (###p < 0.001 vs. non-treated group) lower than the nontreated group. Methylglyoxal (MGO) significantly (***p < 0.001) reduced cell viability (24.4%) and increased reactive oxygen species (ROS) level (642.3%), MGO accumulation (119.4 ㎍/mL), and apoptosis (55.0%) in mesangial cells compared to the nontreated group. Pretreatment with CSE significantly (###p < 0.001) increased cell viability (57.8%) and decreased intracellular ROS (96.5%), MGO accumulation (80.0 ㎍/mL), and apoptosis (22.6%) at 20 ㎍/mL. Additionally, we confirmed intracellular AGEs reduction by CSE pretreatment. Consequently, our results suggest that CSE is a good source of natural therapeutics for managing diabetic complications by the antiglycation effect and renal protective activity against MGO-induced oxidative stress.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.408-419
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• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• Kidney Research and Clinical Practice
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• v.35 no.2
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• pp.69-77
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• 2016

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and its pathogenesis is complex and has not yet been fully elucidated. Abnormal glucose and lipid metabolism is key to understanding the pathogenesis of DN, which can develop in both type 1 and type 2 diabetes. A hallmark of this disease is the accumulation of glucose and lipids in renal cells, resulting in oxidative and endoplasmic reticulum stress, intracellular hypoxia, and inflammation, eventually leading to glomerulosclerosis and interstitial fibrosis. There is a growing body of evidence demonstrating that dysregulation of 50 adenosine monophosphate-activated protein kinase (AMPK), an enzyme that plays a principal role in cell growth and cellular energy homeostasis, in relevant tissues is a key component of the development of metabolic syndrome and type 2 diabetes mellitus; thus, targeting this enzyme may ameliorate some pathologic features of this disease. AMPK regulates the coordination of anabolic processes, with its activation proven to improve glucose and lipid homeostasis in insulin-resistant animal models, as well as demonstrating mitochondrial biogenesis and antitumor activity. In this review, we discuss new findings regarding the role of AMPK in the pathogenesis of DN and offer suggestions for feasible clinical use and future studies of the role of AMPK activators in this disorder.