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drug-induced nephrotoxicity

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https://www.readbyqxmd.com/read/29775647/exposure-to-imipenem-cilastatin-causes-nephrotoxicity-and-even-urolithiasis-in-wistar-rats
#1
Amal Tahri, Amina Lahyani, Rim Kallel, Fatma Ayadi, Tahia Boudawara, Zouheir Sahnoun
Imipenem/cilastatin is a broad-spectrum β-lactam antibiotic used to treat several bacterial infections. The present study was designed to validate the nephrotoxic effect of this drug in rats and to explore its potentional urolithiatic effect. Thirty two Wistar rats were randomly divided into four groups: three experimental groups treated with different imipenem/cilastatin dosages (30, 50 and 80 mg/kg/day) and a control group.The experimental groups were given intraperitoneal imipenem/cilastatin injections twice daily for 7 days, and the control group was given intraperitoneal vehicle NaCl 0...
May 15, 2018: Toxicology
https://www.readbyqxmd.com/read/29767558/molecular-basis-of-the-counteraction-by-calcium-channel-blockers-of-cyclosporine-nephrotoxicity
#2
Safaa Hicham Hammoud, Sahar Alkhansa, Neamah Mahjoub, Amal Galal Omar, Mahmoud M El-Mas, Assaad A Eid
Nephrotoxicity is a serious side effect for the immunosuppressant drug cyclosporine (CSA). In this study, we tested the hypothesis that administration of calcium channel blockers such as verapamil or nifedipine ameliorate renal CSA-induced renal dysfunction. Furthermore, our study investigates the roles of inflammatory, oxidative, and fibrotic pathways in CSA-induced renal dysfunction. Six groups of male rats (n=6/group) were used and received one of the following treatments for 7 consecutive days: vehicle (cremophor EL, i...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29767555/protective-effect-of-the-bet-protein-inhibitor-jq1-in-cisplatin-induced-nephrotoxicity
#3
Liping Sun, Jing Liu, Yanggang Yuan, Xinzhou Zhang, Zheng Dong
As a potent chemotherapy drug, cisplatin is also notorious for its side effects including nephrotoxicity in kidneys, presenting a pressing need to identify renoprotective agents. Cisplatin nephrotoxicity involves epigenetic regulations, including changes in histone acetylation. Bromodomain and extra-terminal (BET) proteins are "readers" of the epigenetic code of histone acetylation. Here, we investigated the potential renoprotective effects of JQ1, a small molecule inhibitor of BET proteins. We show that JQ1 significantly ameliorated cisplatin-induced nephrotoxicity in mice as indicated by the measurements of kidney function, histopathology, and renal tubular apoptosis...
May 16, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29761868/evaluating-the-use-of-kim-1-in-drug-development-and-research-following-fda-qualification
#4
Ru Chen, Sarmistha Sanyal, Aliza Thompson, Joachim H Ix, Kylie Haskins, Laurie Muldowney, Shashi Amur
The Biomarker Qualification Program was established at the Center for Drug Evaluation and Research (CDER), Food and Drug Administration (FDA) to expedite the integration of promising biomarkers across multiple drug development programs. The first set of biomarkers qualified in 2008 consisted of seven nonclinical safety biomarkers for the detection of acute drug-induced nephrotoxicity in rats, and included urinary kidney injury molecule-1 (KIM-1). This article discusses the use of KIM-1 in drug development and research before and after CDER's qualification of KIM-1...
May 15, 2018: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/29760126/experimental-amphotericin-b-deoxycholate-formulations-for-pulmonary-aspergillosis-efficacy-biodistribution-and-nephrotoxicity
#5
Alicia López-Sánchez, Alba Pérez-Cantero, Carlos Torrado-Salmerón, Adela Martin-Vicente, Víctor García-Herrero, María Ángeles González-Nicolás, Alberto Lázaro, Alberto Tejedor, Santiago Torrado-Santiago, Juan José García-Rodríguez, Javier Capilla, Susana Torrado
An experimental micellar formulation of amphotericin B (AMB) with sodium deoxycholate (DCH), AMB:DCH 1:1.5, was obtained and characterized to determine its aggregation state and particle size. Biodistribution, nephrotoxicity and efficacy against pulmonary aspergillosis in a murine model were studied and compared to the liposomal commercial amphotericin B after intravenous administration. The administration of 5 mg/kg AMB:DCH 1:1.5 presented 2.8-fold higher lung concentrations (18.125 ± 3.985 μg/g, after 6 daily doses) and lower kidney exposure (0...
May 14, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29755347/honokiol-a-polyphenol-natural-compound-attenuates-cisplatin-induced-acute-cytotoxicity-in-renal-epithelial-cells-through-cellular-oxidative-stress-and-cytoskeleton-modulations
#6
Tse-En J Wang, Hung-Ting Liu, Yu-Hua Lai, Tong-Rong Jan, Naohiro Nomura, Hui-Wen Chang, Chi-Chung Chou, Ya-Jane Lee, Pei-Shiue J Tsai
Cisplatin is a potent anti-cancer drug that has been widely used in the treatment of various cancers; however, cisplatin administration results in severe nephrotoxicity and impedes its clinical applications. In this study, we showed that honokiol, a polyphenol constituent extracted from Magnolia officinalis exhibited a short-term protective effect against cisplatin-induced damages in renal epithelial cells in vitro . The protective effects of honokiol were resulted from the combination of (1) reduced cellular oxidative stress ranging from 53 to 32% reduction during a 24-h incubation, (2) the maintenance of cellular antioxidant capacity and (3) the stabilization of cytoskeletal structure of the kidney epithelial cells...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29753739/effect-of-cisplatin-on-the-clock-genes-expression-in-the-liver-heart-and-kidney
#7
Bei-Bei Cao, Dengfeng Li, Xiaoliang Xing, Yaguang Zhao, Kunyang Wu, Fang Jiang, Wei Yin, Jia-Da Li
Cisplatin is a platinum-based chemotherapy drug is widely used to treat various types of malignancies. Although the involvement of circadian clock in cisplatin metabolism and excretion has been reported, the effect of cisplatin on circadian rhythm remains unclear. In the present study, we investigated the effects of cisplatin on clock genes expression in mouse peripheral tissues. Cisplatin induced severe nephrotoxicity, as revealed by the significant increase of blood urea nitrogen and serum creatinine levels...
May 10, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29750317/mycophenolate-mofetil-for-sustained-remission-in-nephrotic-syndrome
#8
Uwe Querfeld, Lutz T Weber
The clinical application of mycophenolate mofetil (MMF) has significantly widened beyond the prophylaxis of acute and chronic rejections in solid organ transplantation. MMF has been recognized as an excellent treatment option in many immunologic glomerulopathies. For children with frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS) experiencing steroid toxicity, MMF has been recommended as a steroid-sparing drug. Uncontrolled studies in patients with FRNS and SDSN have shown that many patients can achieve sustained remission of proteinuria with MMF monotherapy...
May 11, 2018: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29749987/the-preventive-role-of-pioglitazone-in-glycerol-induced-acute-kidney-injury-in-rats-during-two-different-treatment-periods
#9
Rama Mousleh, Shaza Al Laham, Ahmad Al-Manadili
Background: Acute kidney injury is the most life-threatening complication of rhabdomyolysis. Glycerol is commonly used to induce this injury. The aim was to investigate the renoprotective effects of pioglitazone and the possible advantage of administering the drug for a longer period. Methods: Twenty-four male Albino Wistar rats were randomly divided into 4 groups (n=6/group): (A) control, (B) glycerol (50%, 10 mL/kg intramuscularly), (C) glycerol+pioglitazone (10 mg/kg orally for 3 days), and (D) glycerol+pioglitazone (for 6 days)...
March 2018: Iranian Journal of Medical Sciences
https://www.readbyqxmd.com/read/29738030/renal-oncocytoma-in-a-kidney-transplant-patient-the-imaging-features-on-contrast-enhanced-ultrasonography-ceus-a-case-report
#10
Lucia Alejandra Alfaro Villanueva, Maira Knust, Leonardo Quintella, José Hermógenes R Suassuna, Nordeval C Araújo
Renal oncocytoma is an infrequently reported renal neoplasm, often asymptomatic, which usually behaves as a benign entity and is identified accidentally on radiological imaging. Transplant patients under long-term immunosuppressive drugs have a high prevalence of cancers, such as skin cancers, lymphoproliferative disorders, and renal carcinomas. We present a case report of an asymptomatic renal oncocytoma in a kidney transplant recipient presenting persistent hematuria. The features of computed tomography and contrast-enhanced ultrasound (CEUS) are presented...
April 19, 2018: Jornal Brasileiro de Nefrologia: ʹorgão Oficial de Sociedades Brasileira e Latino-Americana de Nefrologia
https://www.readbyqxmd.com/read/29737591/expression-profile-of-markers-of-oxidative-stress-injury-and-apoptosis-in-anti-tuberculosis-drugs-induced-nephrotoxicity
#11
Radhika Sharma, Priya Battu, Mandakini Singla, Neha Goyal, Vijay L Sharma
AIM: Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA) are part of first-line anti-tuberculosis therapy used against infection caused by Mycobacterium tuberculosis. However these drugs are known to be potentially harmful as these are associated with numerous side effects and when taken together their harmful outcomes are elevated in a synergistic manner. Identification of possible mechanism underlying RIF+INH+PZA induced nephrotoxicity may be advantageous in developing strategies to prevent their toxic implications...
May 8, 2018: Nephrology
https://www.readbyqxmd.com/read/29735908/protective-effect-of-artemisia-argyi-and-its-flavonoid-constituents-against-contrast-induced-cytotoxicity-by-iodixanol-in-llc-pk1-cells
#12
Dahae Lee, Chang-Eop Kim, Sa-Yoon Park, Kem Ok Kim, Nguyen Tuan Hiep, Dongho Lee, Hyuk-Jai Jang, Jae Wook Lee, Ki Sung Kang
Preventive effects and corresponding molecular mechanisms of mugwort ( Artemisia argyi ) extract and its flavonoid constituents on contrast-induced nephrotoxicity were explored in the present study. We treated cultured LLC-PK1 cells with iodixanol to induce contrast-induced nephrotoxicity, and found that A. argyi extracts ameliorated the reduction in cellular viability following iodixanol treatment. The anti-apoptotic effect of A. argyi extracts on contrast-induced nephrotoxicity was mediated by the inhibition of mitogen-activated protein kinase (MAPK) phosphorylation and the activation of caspases...
May 7, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29735688/cisplatin-dna-adduct-repair-of-transcribed-genes-is-controlled-by-two-circadian-programs-in-mouse-tissues
#13
Yanyan Yang, Ogun Adebali, Gang Wu, Christopher P Selby, Yi-Ying Chiou, Naim Rashid, Jinchuan Hu, John B Hogenesch, Aziz Sancar
Cisplatin is a major cancer chemotherapeutic drug. It kills cancer cells by damaging their DNA, mainly in the form of Pt-d(GpG) diadducts. However, it also has serious side effects, including nephrotoxicity and hepatotoxicity that limit its usefulness. Chronotherapy is taking circadian time into account during therapy to improve the therapeutic index, by improving efficacy and/or limiting toxicity. To this end, we tested the impact of clock time on excision repair of cisplatin-induced DNA damage at single-nucleotide resolution across the genome in mouse kidney and liver...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29725494/the-encapsulation-of-lycopene-in-nanoliposomes-enhances-its-protective-potential-in-methotrexate-induced-kidney-injury-model
#14
Nenad Stojiljkovic, Sonja Ilic, Vladimir Jakovljevic, Nikola Stojanovic, Slavica Stojnev, Hristina Kocic, Marko Stojanovic, Gordana Kocic
Methotrexate is an antimetabolic drug with a myriad of serious side effects including nephrotoxicity, which presumably occurs due to oxidative tissue damage. Here, we evaluated the potential protective effect of lycopene, a potent antioxidant carotenoid, given in two different pharmaceutical forms in methotrexate-induced kidney damage in rats. Serum biochemical (urea and creatinine) and tissue oxidative damage markers and histopathological kidney changes were evaluated after systemic administration of both lycopene dissolved in corn oil and lycopene encapsulated in nanoliposomes...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29725301/necrostatin-1-attenuates-cisplatin-induced-nephrotoxicity-through-suppression-of-apoptosis-and-oxidative-stress-and-retains-klotho-expression
#15
Yichun Ning, Yiqin Shi, Jing Chen, Nana Song, Jieru Cai, Yi Fang, Xiaofang Yu, Jun Ji, Xiaoqiang Ding
Aim: Cisplatin is an effective chemotherapeutic drug, but the application in clinical is greatly limited by its nephrotoxicity. Necrostatin-1 (Nec-1), an inhibitor of RIP1 kinase, has been reported to inhibit RIP-mediated necroptosis. The aim of this study is to detect the protective effects of Nec-1 on the nephrotoxicity of cisplatin and to investigate its renoprotection mechanism. Methods: 8-week-old male C57BL/6 mice were randomly assigned into four groups: Control, Nec-1, Cisplatin, and Cisplatin+Nec-1...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29716853/fermentation-of-aristolochia-debilis-by-six-different-medicinal-fungi-and-identification-of-aristolochic-acid-derivates-in-their-products-by-hplc-esi-tof-ms
#16
Xuexiang Liu, Jing Cao, Yang Pan, Xian Zhang
To analyze the content change of the nephrotoxic substances, aristolochic acid derivates (AAs) in the roots of Aristolochia debilis and the products generated from the solid-state fermentation of six different medicinal fungi by HPLC-ESI-TOF-MS, the chromatographic separation was carried out on C18 column at 30°C with the DAD detector. The elution was performed using the mobile phase of acetonitrile (A) and 0.2% acetic acid (B). Several new peaks were found in the scale of 0-20 min elution of HPLC diagram in the fermentation products...
May 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29706358/the-role-of-cannabinoid-signaling-in-acute-and-chronic-kidney-diseases
#17
REVIEW
Federica Barutta, Graziella Bruno, Raffaella Mastrocola, Stefania Bellini, Gabriella Gruden
The endogenous cannabinoids anandamide and 2-arachidonoylglycerol bind to the cannabinoid receptors of type 1 and 2. These receptors are also the binding sites for exogenous, both natural and synthetic, cannabinoids that are used for recreation purposes. Until recently, cannabinoids and cannabinoid receptors have attracted little interest among nephrologists; however, a full endocannabinoid system (ECS) is present in the kidney and it has recently emerged as an important player in the pathogenesis of diabetic nephropathy, drug nephrotoxicity, and progressive chronic kidney disease...
April 26, 2018: Kidney International
https://www.readbyqxmd.com/read/29695796/mitochondrial-nadp-dependent-isocitrate-dehydrogenase-deficiency-increases-cisplatin-induced-oxidative-damage-in-the-kidney-tubule-cells
#18
Min Jung Kong, Sang Jun Han, Jee In Kim, Jeen-Woo Park, Kwon Moo Park
Mitochondrial NADP+ -dependent isocitrate dehydrogenase (IDH2) plays an important role in the formation of NADPH, which is critical for the maintenance of mitochondrial redox balance. Cis-diamminedichloroplatinum II (cisplatin), an effective anticancer drug, induces oxidative stress-related nephrotoxicity, limiting its use. Therefore, we investigated whether IDH2, which is a critical enzyme in the NADPH-associated mitochondrial antioxidant system, is involved in cisplatin nephrotoxicity. Idh2 gene-deleted (Idh2-/- ) mice and wild-type (Idh2 +/+ ) littermates were treated with cisplatin, with or without 2-(2,2,6,6-tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (Mito-T), a mitochondria-specific antioxidant...
April 25, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29686775/beneficial-effects-of-cynaroside-on-cisplatin-induced-kidney-injury-in-vitro-and-in-vivo
#19
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/29679655/n-acetylcysteine-transforms-necrosis-into-apoptosis-and-affords-tailored-protection-from-cisplatin-cytotoxicity
#20
Sandra M Sancho-Martínez, Laura Prieto-García, Marta Prieto, Isabel Fuentes-Calvo, José M López-Novoa, Ana I Morales, Carlos Martínez-Salgado, Francisco J López-Hernández
Nephrotoxicity is the main limitation to the dosage and anticancer efficacy of cisplatin. Cisplatin produces tubular epithelial cell apoptosis and necrosis depending on the concentration of the drug. Protection from cisplatin nephrotoxicity must therefore tackle both cell death modes. For its ability to reduce cisplatin reactivity, in addition to its antioxidant effect, we tested and found that N-acetylcysteine (NAC) was most effective at inhibiting cisplatin cytotoxicity. NAC has no significant effect on cell death induced by either cycloheximide or Fas activation, indicating a rather selective action...
April 18, 2018: Toxicology and Applied Pharmacology
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