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https://www.readbyqxmd.com/read/29686775/beneficial-effects-of-cynaroside-on-cisplatin-induced-kidney-injury-in-vitro-and-in-vivo
#1
Jong-Hyun Nho, Ho-Kyung Jung, Mu-Jin Lee, Ji-Hun Jang, Mi-Ok Sim, Da-Eun Jeong, Hyun-Woo Cho, Jong-Choon Kim
Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that 10 μM cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells...
April 2018: Toxicological Research
https://www.readbyqxmd.com/read/29682100/urinary-clusterin-is-upregulated-in-nephropathia-epidemica
#2
Ekaterina V Martynova, Adelya N Maksudova, Venera G Shakirova, Sayar R Abdulkhakov, Ilsiyar M Khaertynova, Vladimir A Anokhin, Vilena V Ivanova, Ilesanmi M Abiola, Ekaterina E Garanina, Leisan G Tazetdinova, Aigul H Valiullina, Svetlana F Khaiboullina
Kidney insufficiency is a hallmark of nephropathia epidemica (NE). Little is known about the mechanisms of the NE kidney pathology, with current knowledge mainly based on findings in postmortem tissue. We have analyzed kidney damage biomarkers in urine collected from early- and late-phase NE using Bio-Plex kidney toxicity panels 1 and 2. To determine the disease specificity, kidney damage biomarkers were also analyzed in urine samples from patients diagnosed with gout, type 2 diabetes, systemic lupus erythematosus, and chronic kidney insufficiency...
2018: Disease Markers
https://www.readbyqxmd.com/read/29679048/disruption-of-hox9-10-11-function-results-in-cellular-level-lineage-infidelity-in-the-kidney
#3
Keri A Drake, Mike Adam, Robert Mahoney, S Steven Potter
Hox genes are important regulators of development. The 39 mammalian Hox genes have considerable functional overlap, greatly confounding their study. In this report, we generated mice with multiple combinations of paralogous and flanking Abd-B Hox gene mutations to investigate functional redundancies in kidney development. The resulting mice developed a number of kidney abnormalities, including hypoplasia, agenesis, and severe cysts, with distinct Hox functions observed in early metanephric kidney formation and nephron progenitor maintenance...
April 20, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29678998/acid-stimulation-of-the-citrate-transporter-nadc-1-requires-pyk2-and-erk1-2-signaling-pathways
#4
Miriam Zacchia, Xuefei Tian, Enrica Zona, Robert J Alpern, Patricia A Preisig
Background Urine citrate is reabsorbed exclusively along the renal proximal tubule via the apical Na+ -dicarboxylate cotransporter NaDC-1. We previously showed that an acid load in vivo and media acidification in vitro increase NaDC-1 activity through endothelin-1 (ET-1)/endothelin B (ETB ) signaling. Here, we further examined the signaling pathway mediating acid-induced NaDC-1 activity. Methods We transiently transfected cultured opossum kidney cells, a model of the proximal tubule, with NaDC-1 and ETB and measured [14 C]-citrate uptake after media acidification under various experimental conditions, including inactivation of Pyk2 and c-Src, which were previously shown to be activated by media acidification...
April 20, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29674665/the-proximal-tubular-%C3%AE-7-nicotinic-acetylcholine-receptor-attenuates-ischemic-acute-kidney-injury-through-akt-pkc-signaling-mediated-ho-1-induction
#5
Hwajin Kim, So Ra Kim, Jihyun Je, Kyuho Jeong, Sooji Kim, Hye Jung Kim, Ki Churl Chang, Sang Won Park
Activation of the α7 nicotinic acetylcholine receptor (α7nAChR) has been shown to attenuate excessive inflammation by inhibiting proinflammatory cytokines during ischemia-reperfusion (IR) injury; however, the underlying kidney-specific molecular mechanisms remain unclear. The protective action of α7nAChR against renal IR injury was investigated using a selective α7nAChR agonist and antagonist. α7nAChR activation reduced plasma creatinine levels and tubular cell damage, whereas α7nAChR inhibition aggravated the IR-induced phenotype...
April 20, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29673704/synergistic-action-of-the-nephrotoxic-mycotoxins-ochratoxin-a-and-citrinin-at-nanomolar-concentrations-in-human-proximal-tubule-derived-cells
#6
Marie-Christin Schulz, Luise Schumann, Ulrike Rottkord, Hans-Ulrich Humpf, Michael Gekle, Gerald Schwerdt
Increased ochratoxin A (OTA) or citrinin (CIT) concentrations in food correlate with increased prevalence of tubule-interstitial nephropathy. We tested the hypothesis that co-exposure of human proximal tubule-derived epithelial cells (HK-2) to OTA and CIT promotes synergistic events indicative for inflammation, epithelial-to-mesenchymal-transition (EMT) or fibrosis. We measured markers of inflammation, EMT and fibrosis and investigated the role of MAP-kinases. Only concurrent but not individual exposure to OTA and CIT at nanomolar concentrations led to (i) an increase of TNF protein and mRNA, (ii) a decrease of COX-2 protein and mRNA, (iii) a decrease of E-cadherin protein and (iv) an increase of vimentin and α-SMA protein...
April 16, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29670094/loss-of-deptor-in-renal-tubules-protects-against-cisplatin-induced-acute-kidney-injury
#7
Caixia Wang, Huaiqian Dai, Zhi Xiong, Qiancheng Song, Zhipeng Zou, Mangmang Li, Jing Nie, Xiaochun Bai, Zhenguo Chen
DEP domain containing mTOR-interacting protein (DEPTOR) was originally identified as an in vivo dual inhibitor of mechanistic target of rapamycin (mTOR). It was recently reported to be involved in renal physiology and pathology in vitro; however, its detailed roles and mechanisms in vivo are completely unknown. We observed that DEPTOR expression in the kidney was markedly increased on day 3 after cisplatin treatment, at which time cell apoptosis peaked, implicating DEPTOR in cisplatin-induced acute kidney injury (AKI)...
April 18, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29669465/superiority-of-rat-over-murine-model-for-studies-on-the-evolution-of-cancer-genome
#8
Shinya Akatsuka, Guang Hua Li, Shinya Toyokuni
Evolution of the species and carcinogenesis are similar in that genomic alterations are the key events. Oxidative stress derived from various etiologies is one of the major causes of carcinogenesis by inducing mutations in the genome. Persistent oxidative stress in the renal proximal tubules through Fenton reaction catalyzed by ferric nitrilotriacetate (Fe-NTA) generates renal cell carcinoma (RCC) in mice and rats. Here, in order to observe the species difference in oxidative stress-induced carcinogenesis and to obtain an insight regarding the characteristics of each species, we compared the genomic alterations using array-based comparative genome hybridization among RCCs in Mutyh knockout/wild-type mice (C57BL/6 background) induced by Fe-NTA, RCCs in F1 hybrids of Brown-Norway/Fischer-344 wild-type rats and clear cell renal cell carcinoma (CCRCC)/papillary renal cell carcinoma (PRCC) of humans...
April 18, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29667911/experimental-heat-stress-nephropathy-and-liver-injury-are-improved-by-allopurinol
#9
Carlos A Roncal-Jimenez, Yuka Sato, Tamara Milagres, Ana Andres-Hernando, Gabriela E Garcia, Petter Bjornstad, Jaime Butler-Dawson, Cecilia Sorensen, Lee Newman, Lyndsay Krisher, Magdalena Madero, Jason Glaser, Ramon Garcia-Trabannino, Emmanuel Jarquin-Romero, Zhilin Song, Thomas Jensen, Masanari Kuwabara, Bernardo Rodriguez-Iturbe, Laura-Gabriela Sanchez-Lozada, Miguel A Lanaspa, Richard J Johnson
BACKGROUND: An epidemic of chronic kidney disease (CKD) has been observed in Central America among workers in the sugarcane fields. One hypothesis is that the CKD may be caused by recurrent heat stress and dehydration, and potentially by hyperuricemia. Accordingly, we developed a murine model of kidney injury associated with recurrent heat stress. In the current experiment, we tested whether treatment with allopurinol (a xanthine oxidase inhibitor that reduces serum urate) provides renal protection against recurrent heat stress and dehydration...
April 18, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29666283/the-origin-dynamic-morphology-and-pi4p-independent-formation-of-encephalomyocarditis-virus-replication-organelles
#10
C E Melia, H M van der Schaar, A W M de Jong, H R Lyoo, E J Snijder, A J Koster, F J M van Kuppeveld, M Bárcena
Picornaviruses induce dramatic rearrangements of endomembranes in the cells that they infect to produce dedicated platforms for viral replication. These structures, termed replication organelles (ROs), have been well characterized for the Enterovirus genus of the Picornaviridae However, it is unknown whether the diverse RO morphologies associated with enterovirus infection are conserved among other picornaviruses. Here, we use serial electron tomography at different stages of infection to assess the three-dimensional architecture of ROs induced by encephalomyocarditis virus (EMCV), a member of the Cardiovirus genus of the family of picornaviruses that is distantly related...
April 17, 2018: MBio
https://www.readbyqxmd.com/read/29663893/sglt-2-inhibition-novel-therapeutics-for-reno-and-cardioprotection-in-diabetes-mellitus
#11
Angus Gill, Stephen P Gray, Karin A Jandeleit-Dahm, Anna M D Watson
BACKGROUND: The sodium glucose co-transporter 2 (SGLT2) is primarily located within S1 of the renal proximal tubule being responsible for approximately 90% of glucose re-uptake in the kidney. Inhibition of SGLT2 is an exciting new pharmacological approach for the reduction of blood glucose in type 2 diabetic patients via inhibition of tubular glucose reabsorption. In addition to lowering glucose, this group of drugs has shown significant cardiovascular and renal protective effects. CONCLUSION: This review aims to outline the current state of preclinical research and clinical trials for different SGLT2 inhibitors and outline some of the proposed mechanisms of action, including possible effects on sympathetic nerve activity, which may contribute to the unexpected beneficial cardiovascular and reno-protective effects of this class of compounds...
April 17, 2018: Current Diabetes Reviews
https://www.readbyqxmd.com/read/29663292/the-potential-role-of-sglt2-inhibitors-in-the-treatment-of-type-1-diabetes-mellitus
#12
Hadi Fattah, Volker Vallon
Type 1 diabetes mellitus is a difficult disease to treat due to the relative paucity of therapeutic options other than injectable insulin. The latter, however, can induce hypoglycemia, which has been linked to enhanced cardiovascular risk. Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-hyperglycemic medications that do not increase the hypoglycemia risk and are US Food and Drug Administration (FDA) approved in type 2 diabetes mellitus. SGLT2 inhibitors may also be of benefit in type 1 diabetic patients, in addition to insulin, although they have not yet been approved for this indication...
April 16, 2018: Drugs
https://www.readbyqxmd.com/read/29660027/the-6-hydroxychromanol-derivative-sul-109-ameliorates-renal-injury-after-deep-hypothermia-and-rewarming-in-rats
#13
Pieter C Vogelaar, Maurits Roorda, Edwin L de Vrij, Martin C Houwertjes, Maaike Goris, Hjalmar Bouma, Adrianus C van der Graaf, Guido Krenning, Robert H Henning
Background: Mitochondrial dysfunction plays an important role in kidney damage in various pathologies, including acute and chronic kidney injury and diabetic nephropathy. In addition to the well-studied ischaemia/reperfusion (I/R) injury, hypothermia/rewarming (H/R) also inflicts acute kidney injury. Substituted 6-hydroxychromanols are a novel class of mitochondrial medicines that ameliorate mitochondrial oxidative stress and protect the mitochondrial network. To identify a novel 6-hydroxychromanol that protects mitochondrial structure and function in the kidney during H/R, we screened multiple compounds in vitro and subsequently assessed the efficacy of the 6-hydroxychromanol derivatives SUL-109 and SUL-121 in vivo to protect against kidney injury after H/R in rats...
April 11, 2018: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/29655784/aristolochic-acid-i-interferes-with-the-expression-of-blcap-tumor-suppressor-gene-in-human-cells
#14
Ying-Tzu Huang, Ting-Shuan Wu, Chuan-Chen Lu, Feng-Yih Yu, Biing-Hui Liu
Aristolochic acid I (AAI) is a phytocompound that is linked to the progressive renal disease and development of human urothelial carcinoma. The bladder cancer-associated protein (BLCAP) gene exhibits a tumor suppressor function in various tumors, including bladder carcinoma. This study evaluated the effect of AAI on BLCAP expression and its associated mechanism in human cells. Administering AAI to human embryonic kidney cells (HEK293), human proximal tubule epithelial cells (HK-2) and urinary bladder cancer cells (HT-1376) significantly reduced the expression of BLCAP mRNA and protein...
April 12, 2018: Toxicology Letters
https://www.readbyqxmd.com/read/29629958/guanylyl-cyclase-a-in-both-renal-proximal-tubular-and-vascular-endothelial-cells-protects-the-kidney-against-acute-injury-in-rodent-experimental-endotoxemia-models
#15
Hiroaki Kitamura, Daisuke Nakano, Yoshiharu Sawanobori, Takehiko Asaga, Hideki Yokoi, Motoko Yanagita, Masashi Mukoyama, Takeshi Tokudome, Kenji Kangawa, Gotaro Shirakami, Akira Nishiyama
BACKGROUND: Natriuretic peptides are used, based on empirical observations, in intensive care units as antioliguric treatments. We hypothesized that natriuretic peptides prevent lipopolysaccharide-induced oliguria by activating guanylyl cyclase A, a receptor for natriuretic peptides, in proximal tubules and endothelial cells. METHODS: Normal Sprague-Dawley rats and mice lacking guanylyl cyclase A in either endothelial cells or proximal tubular cells were challenged with lipopolysaccharide and assessed for oliguria and intratubular flow rate by intravital imaging with multiphoton microscopy...
April 9, 2018: Anesthesiology
https://www.readbyqxmd.com/read/29629275/human-cd36-overexpression-in-renal-tubules-accelerates-the-progression-of-renal-diseases-in-a-mouse-model-of-folic-acid-induced-acute-kidney-injury
#16
Jong Hwan Jung, Jee Eun Choi, Ju Hung Song, Seon-Ho Ahn
Background: Acute kidney injury (AKI) is a risk factor for progression to chronic kidney disease, with even subclinical AKI episodes progressing to chronic kidney disease. Several risk factors such as preexisting kidney disease, hyperglycemia, and hypertension may aggravate renal disease after AKI. However, mechanisms underlying the progression of AKI are still unclear. This study identified the effect of human cluster of differentiation 36 (CD36) overexpression on the progression of folic acid-induced AKI...
March 2018: Kidney Research and Clinical Practice
https://www.readbyqxmd.com/read/29626002/evaluating-off-label-uses-of-acetazolamide
#17
REVIEW
Megan A Van Berkel, Jessica L Elefritz
PURPOSE: Current off-label uses of acetazolamide in hospitalized patients are reviewed. SUMMARY: Acetazolamide is a carbonic anhydrase inhibitor typically used for indications including epilepsy, glaucoma, edema, and altitude sickness but it may be prescribed in hospitalized patients for off-label indications. It inhibits carbonic anhydrase, which leads to reduced hydrogen ion secretion in the proximal renal tubule, resulting in increased bicarbonate and cation excretion and causing urinary alkalization and diuresis...
April 15, 2018: American Journal of Health-system Pharmacy: AJHP
https://www.readbyqxmd.com/read/29620262/dynamic-expression-and-roles-of-sequestome%C3%A2-1-p62-in-lps%C3%A2-induced-acute-kidney-injury-in-mice
#18
Ting Li, Jie Zhao, Shuying Miao, Yunfei Xu, Xianzhong Xiao, Ying Liu
Acute kidney injury (AKI) is one of the most common complications of sepsis. The roles of autophagy in AKI have been demonstrated in previous studies. Sequestosome‑1 (p62) has been demonstrated to serve essential roles in autophagy. The dysregulation of autophagy causes p62 accumulation, which is associated with increased inflammation and tumorigenesis. However, the expression patterns and role of p62 in septic AKI remain unknown. The present study detected the renal autophagy level, and the expression and localization of p62, in a lipopolysaccharide (LPS)‑induced AKI mouse model...
March 28, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29619879/cisplatin-induced-oxidative-stress-stimulates-renal-fas-ligand-shedding
#19
Hitesh Soni, Damian Kaminski, Rajashekhar Gangaraju, Adebowale Adebiyi
Acute kidney injury (AKI), a significant complication of cisplatin chemotherapy is associated with reactive oxygen species (ROS)-dependent renal cell death, but the cellular targets of ROS in cisplatin nephrotoxicity are not fully resolved. Here, we investigated cisplatin-induced oxidative renal damage and tested the hypothesis that ROS-dependent shedding of death activator Fas ligand (FasL) occurs in cisplatin nephropathy. We show that intraperitoneal injection of sulfobutyl ether-β-cyclodextrin (Captisol™)-solubilized cisplatin elevated the level of lipid peroxidation product malondialdehyde in mouse kidneys and urinary concentration of oxidative DNA damage biomarker 8-hydroxy-2'-deoxyguanosine...
November 2018: Renal Failure
https://www.readbyqxmd.com/read/29618297/influence-of-a-single-point-mutation-in-the-constant-domain-of-the-bence-jones-protein-bif-on-its-aggregation-properties
#20
M A Timchenko, A A Timchenko
Multiple myeloma nephropathy occurs due to the aggregate formation by monoclonal immunoglobulin light chains (Bence-Jones proteins) in kidneys of patients with multiple myeloma. The mechanism of amyloid deposit formation is still unclear. Earlier, the key role in the fibril formation has been assigned to the variable domains that acquired amyloidogenic properties as a result of somatic mutations. However, fibril formation by the Bence-Jones protein BIF was found to be the function of its constant domain. The substitution of Ser177 by Asn in the constant domain of the BIF protein is most likely an inherited than a somatic mutation...
February 2018: Biochemistry. Biokhimii︠a︡
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