• International Journal of Stem Cells
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• v.16 no.1
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• pp.52-65
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• 2023

Background and Objectives: Epithelial-Mesenchymal transition (EMT) is one of the origins of myofibroblasts in renal interstitial fibrosis. Mesenchymal stem cells (MSCs) alleviating EMT has been proved, but the concrete mechanism is unclear. To explore the mechanism, serum-free MSCs conditioned medium (SF-MSCs-CM) was used to treat rat renal tubular epithelial cells (NRK-52E) fibrosis induced by transforming growth factor-β1 (TGF-β1) which ameliorated EMT. Methods and Results: Galectin-3 knockdown (Gal-3 KD) and overexpression (Gal-3 OE) lentiviral vectors were established and transfected into NRK-52E. NRK-52E fibrosis model was induced by TGF-β1 and treated with the SF-MSCs-CM for 24 h after modelling. Fibrosis and autophagy related indexes were detected by western blot and immunocytochemistry. In model group, the expressions of α-smooth muscle actin (α-SMA), fibronectin (FN), Galectin-3, Snail, Kim-1, and the ratios of P-Akt/Akt, P-GSK3β/GSK3β, P-PI3K/PI3K, P-mTOR/mTOR, TIMP1/MMP9, and LC3B-II/I were obviously increased, and E-Cadherin (E-cad) and P62 decreased significantly compared with control group. SF-MSCs-CM showed an opposite trend after treatment compared with model group. Whether in Gal-3 KD or Gal-3 OE NRK-52E cells, SF-MSCs-CM also showed similar trends. However, the effects of anti-fibrosis and enhanced autophagy in Gal-3 KD cells were more obvious than those in Gal-3 OE cells. Conclusions: SF-MSCs-CM probably alleviated the EMT via inhibiting Galectin-3/Akt/GSK3β/Snail pathway. Meanwhile, Gal-3 KD possibly enhanced autophagy via inhibiting Galectin-3/Akt/mTOR pathway, which synergistically ameliorated renal fibrosis. Targeting galectin-3 may be a potential target for the treatment of renal fibrosis.

• Journal of the Korean Society of Food Culture
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• v.37 no.6
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• pp.503-509
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• 2022

Methylglyoxal is a highly reactive precursor which forms advanced glycation end products (AGEs). AGEs and methylglyoxal are known to induce various diseases such as diabetes, vascular disorders, Diabetes Mellitus (DM), and neuronal disorders. Juglans regia L is an important food commonly used worldwide, having nutritious components, including phenolic compounds. Since ancient times, Juglans regia L have been differently applied by various countries for health and in diverse diseases, including arthritis, asthma, skin disorders, cancer, and diabetes mellitus. However, the effect of diabetes-induced renal damage against AGEs remains unclear. This study evaluates the anti-glycation and renal protective effects of ethanol extract of Juglans regia L against methylglyoxal-induced renal tubular epithelial cell death. Exposure to methylglyoxal resulted in reduced cell viability in NRK-52E cells, but co-treatment with Juglans regia L extracts significantly increased the cell viability. In addition, we examined the anti-glycation effect of Juglans regia L extracts. Compared to the positive control aminoguanidine and Alagebrium, treatment with Juglans regia L extracts significantly inhibited the formation of AGEs, collagen cross-linking, and breaking collagen cross-linking. Taken together, our results indicate that Juglans regia L is a potential therapeutic agent for regulating diabetic complications by exerting anti-glycation and renal protective activities.

• Journal of Acupuncture Research
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• v.15 no.2
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• pp.331-348
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• 1998

Purpose: In order to study the therapeutic effect of TBR(Smilacis glabrae Rhizoma) aqua-acupuncture on the $HgCI_2$(mercury bichloride) intoxicated kidneys of rats. Methods: 10% TBR extract solution was aqua-punctured into the bilateral loci of Shin-su(BL23), every other day for 18 days, and the amount of leucocytes, erythrocytes, thrombocytes, hematocrit, hemoglobin, serum BUN and creatinine levels were measured and renal mercury level and histopathological findings were studied as well. The experimental groups were into nonmaI group, control group, sample I group, sample II group and sample III group. Results: 1. There were not any significant changes of leucocytes, erythrocytes and serum creatinine level in the TBR aqua-acupuncture group, saline aqua-acupuncture group and TBR aqua-acupuncture group respectively as compared with control group. 2. It showed a significant increase of hematocrit and hemoglobin level in the TBR aqua-acupuncture group on the 8th experimental day as compared with the control group. 3. It showed a significant increase of platelet in the TBR aqua-acupuncture group on the 8th experimental day, whereas significant decreases on the 18th experimental day as compared with the control group. 4. It showed a significant decrease of serum BUN level in the TBR aqua-acupuncture group on the 8th and 18th experimental day as compared with the control group. 5. It showed a significant decrease of renal mercury level in the TBR aqua-acupuncture group on compared with the control group. 6. In the histopathological findings, TBR aqua-acupuncture group showed slight atrophy of the renal tubules, mitosis and regeneration of tubular lining cells with visible nuclei, whereas the control group showed acute tubular necrosis, especially severe necrosis of tubular epithelial cells. Conclusions: Smilacis glabrae Rhizoma aqua-acupuncture on injured kidneys Induced by HgCl2 Intoxication in Rats increases hematocrit, hemoglobin and platelet level, and decreases BUN, renal mercury level. This suggests that Smilacis glabrae Rhizoma aqua-acupuncture helps to recover kidney from HgCl2 intoxication.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.599-610
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• 2023

According to recent evidence, ferroptosis is a major cell death mechanism in the pathogenesis of kidney injury and fibrosis. Despite the renoprotective effects of classical ferroptosis inhibitors, therapeutic approaches targeting kidney ferroptosis remain limited. In this study, we assessed the renoprotective effects of melatonin and zileuton as a novel therapeutic strategy against ferroptosis-mediated kidney injury and fibrosis. First, we identified RSL3-induced ferroptosis in renal tubular epithelial HK-2 and HKC-8 cells. Lipid peroxidation and cell death induced by RSL3 were synergistically mitigated by the combination of melatonin and zileuton. Combination treatment significantly downregulated the expression of ferroptosis-associated proteins, 4-HNE and HO-1, and upregulated the expression of GPX4. The expression levels of p-AKT and p-mTOR also increased, in addition to that of NRF2 in renal tubular epithelial cells. When melatonin (20 mg/kg) and zileuton (20 mg/kg) were administered to a unilateral ureteral obstruction (UUO) mouse model, the combination significantly reduced tubular injury and fibrosis by decreasing the expression of profibrotic markers, such as α-SMA and fibronectin. More importantly, the combination ameliorated the increase in 4-HNE levels and decreased GPX4 expression in UUO mice. Overall, the combination of melatonin and zileuton was found to effectively ameliorate ferroptosis-related kidney injury by upregulating the AKT/mTOR/ NRF2 signaling pathway, suggesting a promising therapeutic strategy for protection against ferroptosis-mediated kidney injury and fibrosis.

• Korean Journal of Veterinary Research
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• v.37 no.1
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• pp.41-57
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• 1997

This study was carried out to investigate the effect of selenium on the adriamycininduced renal lesions in male Sprague Dawley rats. A total of 60 Sprague-Dawley male rats were divided into 2 control groups(C1: saline, C2: selenium) and 2 treatment groups(T1: adriamycin, T2: adriamycin+selenium). The rats of the C1 and T1 groups were given normal saline(0.15ml/rat), the rats of the C2 and T2 groups were given sodium selenite(0.5mg/kg) intraperitoneally three days a week for 4 weeks. The treatment groups were dosed intraperitoneally with adriamycin(2mg/kg/day) five days at the second week. Animals were sacrificed at the 1st week, 2nd week and 3rd week after dosing with adriamycin. The morphologic abnormalities of the glomeruli and tubules in the kidney of male rats were examined histopathologically and electron microscopically.The results obtained were as follows : The mean body weight of adriamycin dosed group was significantly decreased as compared with that of control group at 4th week(p<0.05). In adriamycin and selenium dosed group, the mean body weight was decreased until the end of 2nd week but gradually increased from 3rd to 4th week. The histopathological findings of the renal corpuscle in adriamycin dosed group were parietal epithelial cell proliferation, vacuolization of glomerulus, and thickened basement membrane of the parietal epithelium. Proximal convoluted tubules were significantly dilated and the lumens were filled with renal cast. These lesions were generally not very significant in the rats given adriamycin and selenium. The electron microscopical findings of the renal glomerulus in the adriamycin dosed group were focal loss and fusion of the pedicels of the podocyte, and some vacuoles in the cytoplasm of the podocytes. There were numerous cytoplasmic vacuoles in the proximal and distal convoluted tubular cells. However, these ultrastructural changes were not significantly observed in the renal tubules of the rats of adriamycin and selenium dosed group. These results suggest that selenium may act as an inhibitor of the renal lesions induced by adriamycin in male rats.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.567-575
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• 2018

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI.

• Journal of Acupuncture Research
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• v.21 no.3
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• pp.1-12
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• 2004

Objective: This study was undertaken to evaluate the role of lipid peroxidation in oxidant-induced apoptosis and effect of JS on the apoptosis in opossum kidney (OK) cells, an established renal proximal tubular cells. Methods : Exposure of cells to 0.1mM tBHP for 2hr did not induce apoptosis, but subsequent incubation in normal culture medium for 18hr after tBHP treatment induced apoptotic cell death which is dependent of tBHP concentration. Results : JS decreased tBHP-induced apoptotic cell death in a dose-dependent fashion and at concentrations higher than 0.01 mg/ml completely prevented the apoptosis. tBHP-induced apoptosis was prevented by the lipid soluble antioxidant N,N'-diphenyl-p-phenylenediamine (DPPD) and water-soluble antioxidant Trolox. tBHP increased lipid peroxidation, which was inhibited by JS and DPPD. tBHP-induced DNA damage was prevented by JS and DPPD. Conclusion : These results indicate that tBHP induces apoptosis through a lipid peroxidation-dependent mechanism and JS exerts the protective effect against the apoptosis by preventing peroxidation of membrane lipids.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.5
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• pp.529-538
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• 1999

This study was undertaken to examine the effect of ethanol on $Na^+ -dependent$ phosphate $(Na^+-P_i)$ uptake in opossum kidney (OK) cells, an established renal proximal tubular cell line. Ethanol inhibited ^Na^+-dependent$ component of phosphate uptake in a dose-dependent manner with $I_{50}$ of 8.4%, but it did not affect $Na^+-independent$ component. Similarly, ethanol inhibited $Na^+-dependent$ uptakes of glucose and amino acids (AIB, glycine, alanine, and leucine). Microsomal $Na^+-K^+-ATPase$ activity was not significantly altered when cells were treated with 8% ethanol. Kinetic analysis showed that ethanol increased $K_m$ without a change in $V_{max}$ of $Na^+-P_i$ uptake. Inhibitory effect of n-alcohols on $Na^+-P_i$ uptake was dependent on the length of the hydrocarbon chain, and it resulted from the binding of one molecule of alcohol, as indicated by the Hill coefficient (n) of 0.8-1.04. Catalase significantly prevented the inhibition, but superoxide dismutase and hydroxyl radical scavengers did not alter the ethanol effect. A potent antioxidant DPPD and iron chelators did not prevent the inhibition. Pyrazole, an inhibitor of alcohol dehydrogenase, did not attenuate ethanol-induced inhibition of $Na^+-P_i$ uptake, but it prevented ethanol-induced cell death. These results suggest that ethanol may inhibit $Na^+-P_i$ uptake through a direct action on the carrier protein, although the transport system is affected by alterations in the lipid environment of the membrane.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.54 no.5
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• pp.660-667
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• 2021

In recent years, myxosporean infection from the cultured olive flounders Paralichthys olivaceus, have been frequently observed in Jeju island, South Korea. This study aimed to compare histopathological and molecular-biological methods of examining myxosporean infection from these flounders. Samples were obtained from affected individuals exhibiting emaciation or abdominal distention and a polymerase chain reaction (PCR) indicative of Parvicapsular anisocaudata, Enteromyxum leei and Kudoa septempunctata were initiated. Histopathological examination were conducted with H&E stained tissue sections, and then in-situ hybridization (ISH) reaction were processed with selected sections using P. anisocaudata, E. leei, K. septempunctata and Scuticociliate probes. Renal and intestinal tissue degeneration were common symptoms associated with all samples. Sever glomerular and renal tubular degeneration were evident, as were intestinal epithelial desquamation and spore formation in the epithelial cells. The results of conventional PCR analysis and ISH reactions revealed differences, and we suspect that various microparasites may have been associated with the symptoms manifested.

• Biomedical Science Letters
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• v.14 no.4
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• pp.211-218
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• 2008

The purpose of this study was to investigate the effects of dietary Chungkookjang (Korean fermented soybean) powder on blood glucose level, lipid profiles, antioxidant enzymes activities and histological changes in kidney of streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats of three groups including nondiabetic group fed normal diet (NC), diabetic group fed normal diet (DC) and diabetic group fed Chungkookjang diet (DCH; 100 g/kg diet) were reared for 8 weeks. The serum glucose, triglycelide and total lipid levels in the DCH group were significantly lower (P<0.05) than the DC group. The renal xanthine oxidase, catalase and glutathione S-transferase activities in the DC group were significantly higher than the NC group. The xanthine oxidase, superoxide dismutase and glutathione S-transferase activities in the DCH group were significantly lower than the DC group (P<0.05). Tubular epithelial change, such as Armanni-Ebstein cells, was significantly reduced in the DCH group compared to the DC group. In conclusion, these results indicated that Chungkookjang supplement seems to be beneficial to correct the hyperglycemia and hyperlipidemia as well as to protect kidney against diabetic changes.