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drug-induced nephrotoxicity

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https://www.readbyqxmd.com/read/28340076/cisplatin-induced-renal-inflammation-is-ameliorated-by-cilastatin-nephroprotection
#1
Blanca Humanes, Sonia Camaño, Jose Manuel Lara, Venkatta Sabbisetti, María Ángeles González-Nicolás, Joseph V Bonventre, Alberto Tejedor, Alberto Lázaro
Background.: Cisplatin is a potent chemotherapeutic drug whose nephrotoxic effect is a major complication and a dose-limiting factor for antitumoral therapy. There is much evidence that inflammation contributes to the pathogenesis of cisplatin-induced nephrotoxicity. We found that cilastatin, a renal dehydropeptidase-I inhibitor, has protective effects in vitro and in vivo against cisplatin-induced renal damage by inhibiting apoptosis and oxidation. Here, we investigated the potential use of cilastatin to protect against cisplatin-induced kidney injury and inflammation in rats...
March 11, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28337147/3d-proximal-tubule-tissues-recapitulate-key-aspects-of-renal-physiology-to-enable-nephrotoxicity-testing
#2
Shelby M King, J William Higgins, Celina R Nino, Timothy R Smith, Elizabeth H Paffenroth, Casey E Fairbairn, Abigail Docuyanan, Vishal D Shah, Alice E Chen, Sharon C Presnell, Deborah G Nguyen
Due to its exposure to high concentrations of xenobiotics, the kidney proximal tubule is a primary site of nephrotoxicity and resulting attrition in the drug development pipeline. Current pre-clinical methods using 2D cell cultures and animal models are unable to fully recapitulate clinical drug responses due to limited in vitro functional lifespan, or species-specific differences. Using Organovo's proprietary 3D bioprinting platform, we have developed a fully cellular human in vitro model of the proximal tubule interstitial interface comprising renal fibroblasts, endothelial cells, and primary human renal proximal tubule epithelial cells to enable more accurate prediction of tissue-level clinical outcomes...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28335481/genetic-variants-contributing-to-colistin-cytotoxicity-identification-of-tgif1-and-hoxd10-using-a-population-genomics-approach
#3
Michael T Eadon, Ronald J Hause, Amy L Stark, Ying-Hua Cheng, Heather E Wheeler, Kimberly S Burgess, Eric A Benson, Patrick N Cunningham, Robert L Bacallao, Pierre C Dagher, Todd C Skaar, M Eileen Dolan
Colistin sulfate (polymixin E) is an antibiotic prescribed with increasing frequency for severe Gram-negative bacterial infections. As nephrotoxicity is a common side effect, the discovery of pharmacogenomic markers associated with toxicity would benefit the utility of this drug. Our objective was to identify genetic markers of colistin cytotoxicity that were also associated with expression of key proteins using an unbiased, whole genome approach and further evaluate the functional significance in renal cell lines...
March 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28325303/inhibition-of-egf-uptake-by-nephrotoxic-antisense-drugs-in%C3%A2-vitro-and-implications-for-preclinical-safety-profiling
#4
Annie Moisan, Marcel Gubler, Jitao David Zhang, Yann Tessier, Kamille Dumong Erichsen, Sabine Sewing, Régine Gérard, Blandine Avignon, Sylwia Huber, Fethallah Benmansour, Xing Chen, Roberto Villaseñor, Annamaria Braendli-Baiocco, Matthias Festag, Andreas Maunz, Thomas Singer, Franz Schuler, Adrian B Roth
Antisense oligonucleotide (AON) therapeutics offer new avenues to pursue clinically relevant targets inaccessible with other technologies. Advances in improving AON affinity and stability by incorporation of high affinity nucleotides, such as locked nucleic acids (LNA), have sometimes been stifled by safety liabilities related to their accumulation in the kidney tubule. In an attempt to predict and understand the mechanisms of LNA-AON-induced renal tubular toxicity, we established human cell models that recapitulate in vivo behavior of pre-clinically and clinically unfavorable LNA-AON drug candidates...
March 17, 2017: Molecular Therapy. Nucleic Acids
https://www.readbyqxmd.com/read/28321043/immunolocalization-of-novel-corticomedullary-tubule-injury-markers-in-cynomolgus-monkeys-treated-with-amphotericin-b
#5
J Eric McDuffie, Jing Ying Ma, Yunhai Zhang, Frederic S Almy, Xiaoyun Wu, Ke Li, Manisha Sonee, Ryan Meng, Michele Rizzolio, Sandra S Snook
Amphotericin B (AmpB) nephrotoxicity was used to assess the utility of drug‑induced kidney injury (DIKI) biomarkers in an exploratory study in male cynomolgus monkeys. All animals had quantifiable levels of AmpB in plasma on days 1 and 4. There were no clinical signs of AmpB‑induced toxicity in this study. The gold standard method used to confirm AmpB‑induced DIKI was anatomic pathology which revealed microscopic lesions with varying grades of severity. Immunolocalization of alpha‑1 microglobulin (α‑1M), kidney injury molecule 1 (KIM‑1), osteopontin (OPN) and neutrophil gelatinase‑associated lipocalin (NGAL) proteins was evaluated in formalin‑fixed, paraffin‑embedded monkey kidney tissue sections...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28315429/vinpocetine-reduces-diclofenac-induced-acute-kidney-injury-through-inhibition-of-oxidative-stress-apoptosis-cytokine-production-and-nf-%C3%AE%C2%BAb-activation-in-mice
#6
Victor Fattori, Sergio M Borghi, Carla F S Guazelli, Andressa C Giroldo, Jefferson Crespigio, Allan J C Bussmann, Letícia Coelho-Silva, Natasha G Ludwig, Tânia L Mazzuco, Rubia Casagrande, Waldiceu A Verri
Acute kidney injury (AKI) represents a complex clinical condition associated with significant morbidity and mortality. Approximately, 19-33% AKI episodes in hospitalized patients are related to drug-induced nephrotoxicity. Although, considered safe, non-steroidal anti-inflammatory drugs such as diclofenac have received special attention in the past years due to the potential risk of renal damage. Vinpocetine is a nootropic drug known to have anti-inflammatory properties. In this study, we investigated the effect and mechanisms of vinpocetine in a model of diclofenac-induced AKI...
March 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28292990/-nephropathy-in-patients-undergoing-cancer-drug-therapy-platinum-derivatives-cisplatin-and-carboplatin
#7
Ayumu Matsuoka, Yuichi Ando
Cisplatin, a first-generation platinum derivative, is one of the most widely used anticancer agents and can treat a broad spectrum of malignancies. Cisplatin-induced nephrotoxicity is a major dose-limiting side effect resulting from damage to the proximal tubules of the kidney. This nephrotoxicity can be prevented by lowering the concentration of cisplatin and shortening the period of cisplatin exposure to the proximal tubules. In clinical practice, high-volume hydration(>3 L intravenous isotonic saline), forced diuresis(mannitol and/or furosemide), and magnesium supplementation have been generally used to lower the risk of cisplatin-induced nephrotoxicity...
March 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28284381/mechanisms-of-drug-induced-interstitial-nephritis
#8
REVIEW
Rajeev Raghavan, Saed Shawar
Drug-induced acute interstitial nephritis (DI-AIN) is a drug hypersensitivity reaction (DHR) that manifests 7 to 10 days after exposure to the culprit drug. DHRs account for fewer than 15% of reported adverse drug reactions. The kidneys are susceptible to DHR because: (1) the high renal blood flow whereby antigens are filtered, secreted, or concentrated, and (2) it is a major site of excretion for drugs and drug metabolites. More than 250 different drugs from various classes have been incriminated as causative agents of DI-AIN, the third most common cause of acute kidney injury in the hospital...
March 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28272459/enoblock-a-unique-small-molecule-inhibitor-of-the-non-glycolytic-functions-of-enolase-alleviates-the-symptoms-of-type-2-diabetes
#9
Haaglim Cho, JungIn Um, Ji-Hyung Lee, Woong-Hee Kim, Wan Seok Kang, So Hun Kim, Hyung-Ho Ha, Yong-Chul Kim, Young-Keun Ahn, Da-Woon Jung, Darren R Williams
Type 2 diabetes mellitus (T2DM) significantly impacts on human health and patient numbers are predicted to rise. Discovering novel drugs and targets for treating T2DM is a research priority. In this study, we investigated targeting of the glycolysis enzyme, enolase, using the small molecule ENOblock, which binds enolase and modulates its non-glycolytic 'moonlighting' functions. In insulin-responsive cells ENOblock induced enolase nuclear translocation, where this enzyme acts as a transcriptional repressor. In a mammalian model of T2DM, ENOblock treatment reduced hyperglycemia and hyperlipidemia...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28257038/establishment-of-hk-2-cells-as-a-relevant-model-to-study-tenofovir-induced-cytotoxicity
#10
Rachel A Murphy, Reagan M Stafford, Brooke A Petrasovits, Megann A Boone, Monica A Valentovic
Tenofovir (TFV) is an antiviral drug approved for treating Human Immunodeficiency Virus (HIV) and Hepatitis B. TFV is administered orally as the prodrug tenofovir disoproxil fumarate (TDF) which then is deesterified to the active drug TFV. TFV induces nephrotoxicity characterized by renal failure and Fanconi Syndrome. The mechanism of this toxicity remains unknown due to limited experimental models. This study investigated the cellular mechanism of cytotoxicity using a human renal proximal tubular epithelial cell line (HK-2)...
March 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28238158/acute-kidney-injury-during-a-pediatric-sickle-cell-vaso-occlusive-pain-crisis
#11
Sujatha Baddam, Inmaculada Aban, Lee Hilliard, Thomas Howard, David Askenazi, Jeffrey D Lebensburger
BACKGROUND: Patients who develop sickle cell disease (SCD) nephropathy are at a high risk for mortality. The pathophysiology of vaso-occlusive pain crisis may contribute to acute kidney injury (AKI). Non-steroidal anti-inflammatory drugs, known inducers of AKI, are used to treat pain crises. Multiple gaps exist in the knowledge about the impact of AKI in SCD. METHODS: We conducted a 2-year retrospective review of AKI events in patients admitted for vaso-occlusive crisis...
February 25, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/28208010/circulating-plasma-and-exosomal-micrornas-as-indicators-of-drug-induced-organ-injury-in-rodent-models
#12
Young-Eun Cho, Sang-Hyun Kim, Byung-Heon Lee, Moon-Chang Baek
This study was performed to evaluate whether microRNAs (miRNAs) in circulating exosomes may serve as biomarkers of drug-induced liver, kidney, or muscle-injury. Quantitative PCR analyses were performed to measure the amounts of liver-specific miRNAs (miR-122, miR-192, and miR-155), kidney-specific miR-146a, or muscle-specific miR-206 in plasma and exosomes from mice treated with liver, kidney or muscle toxicants. The levels of liver-specific miRNAs in circulating plasma and exosomes were elevated in acetaminophen-induced liver injury and returned to basal levels by treatment with antioxidant N-acetyl-cysteine...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28202365/optimising-the-use-of-medicines-to-reduce-acute-kidney-injury-in-children-and-babies
#13
REVIEW
L Oni, D B Hawcutt, M A Turner, M W Beresford, S McWilliam, C Barton, B K Park, P Murray, B Wilm, I Copple, R Floyd, M Peak, A Sharma, D J Antoine
The majority of medications in children are administered in an unlicensed or off-label manner. Paediatricians are obliged to prescribe using the limited evidence available. The 2007 EU regulation on the use of paediatric drugs means pharmaceutical companies are now obliged to (and receive incentives for) contributing to paediatric drug data and carrying out paediatric clinical trials. This is important, as the efficacy and adverse effect profiles of medicines vary across childhood. Additionally, there are significant age-related changes in the pharmacodynamic and pharmacokinetic activity of many drugs...
February 12, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28177660/carvacrol-attenuates-cyclophosphamide-induced-oxidative-stress-in-rat-kidney
#14
Sibel Gunes, Adnan Ayhanci, Varol Sahinturk, Diler Us Altay, Ruhi Uyar
Cyclophosphamide (CP) is an antineoplastic drug inducing kidney damage via producing oxidative stress. Carvacrol (CAR) has antioxidative effect and we postulated that it can be protective against CP-induced nephrotoxicity. Six groups (n=7) of rats (control, 100 mg/kg CP, CP+5 and CP+10 mg/kg CAR and 5 and 10 mg/kg CAR) were injected intraperitoneally. Serum malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), creatinine (CRE), total antioxidant capacity (TAC) and total oxidant state (TOS) were measured, and oxidative stress indexes (OSI) were calculated...
February 3, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28158949/methionine-sulfoxide-reductase-a-deficiency-exacerbates-cisplatin-induced-nephrotoxicity-via-increased-mitochondrial-damage-and-renal-cell-death
#15
Mi Ra Noh, Ki Young Kim, Sang Jun Han, Jee In Kim, Hwa-Young Kim, Kwon Moo Park
AIMS: Methionine sulfoxide reductase A (MsrA), which is abundantly localized in the mitochondria, reduces methionine-S-sulfoxide, scavenging reactive oxygen species (ROS). Cisplatin, an anticancer drug, accumulates at high levels in the mitochondria of renal cells, causing mitochondrial impairment that ultimately leads to nephrotoxicity. Here, we investigated the role of MsrA in cisplatin-induced mitochondrial damage and kidney cell death using MsrA gene-deleted (MsrA(-/-)) mice. RESULTS: Cisplatin injection resulted in increases of ROS production, methionine oxidation, and oxidative damage in the kidneys...
March 20, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28149008/transforming-growth-factor-%C3%AE-1-smad3-signaling-and-redox-status-in-experimentally-induced-nephrotoxicity-impact-of-carnosine
#16
Walaa Arafa Keshk, Mohamed Alaa Katary
Exposure to various organic compounds including drugs and environmental toxins causes cellular damage through generation of free radicals. Carnosine a dipeptide was used in this study to evaluate its effect against CCl4-induced nephrotoxicity. Sixty male albino rats were involved in this study and were equally divided into four groups. CCl4 (3 ml/kg body weight; biweekly for 4 weeks) was given to group II and III. Carnosine (10 mg/kg body weight; once daily for 4 weeks) was given to group III and VI. Transforming growth factor-β1 (TGF-β1) level by immunoassay and Smad3 mRNA level by real-time PCR were estimated in addition to cytochrome P450 2E1 (CYP2E1) activity, renal functions, redox status assessment and histopathological examination of the kidney...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28144968/adverse-event-due-to-a-likely-interaction-between-sodium-aescinate-and-ginkgo-biloba-extract-a-case-report
#17
H Ji, G Zhang, F Yue, X Zhou
WHAT IS KNOWN AND OBJECTIVE: Drug-induced nephrotoxicity is potentially lethal. When sodium aescinate is given to surgical inpatients to treat postoperative inflammation and oedema, adverse drug reactions and drug-drug interactions must be closely monitored. CASE DESCRIPTION: We report a case of a 58-year-old man with phalangeal fractures who suffered from acute kidney injury that was most likely induced by the drug interaction between sodium aescinate and ginkgo biloba extract due to the protein-binding and metabolic characteristics of these drugs...
February 1, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28141945/drug-induced-renal-injury-in-neonates-challenges-in-clinical-practice-and-perspectives-in-drug-development
#18
Anna Girardi, Emanuel Raschi, Silvia Galletti, Karel Allegaert, Elisabetta Poluzzi, Fabrizio De Ponti
Acute kidney injury (AKI) is frequently diagnosed in the neonatal population, especially in those admitted to intensive care units, and poses several challenges for clinicians mainly because of difficulties in timely identification of renal impairment and the need to administer drugs with potential nephrotoxicity. In this context, research on biomarkers is growing for their implication in the early detection of renal damage and their higher sensitivity in monitoring renal activity, but also as an important tool for drug development...
January 31, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28134775/chrysin-protects-rat-kidney-from-paracetamol-induced-oxidative-stress-inflammation-apoptosis-and-autophagy-a-multi-biomarker-approach
#19
Fatih Mehmet Kandemir, Sefa Kucukler, Eyup Eldutar, Cuneyt Caglayan, İlhami Gülçin
Paracetamol (PC) is a safe analgesic and antipyretic drug at therapeutic doses, and it is widely used in clinics. However, at high doses, it can induce hepatotoxicity and nephrotoxicity. Chrysin (CR) is a natural flavonoid that has biological activities that include being an antioxidant, an anti-inflammatory, and an anti-cancer agent. The main objective of this study was to investigate the efficacy of CR against PC-induced nephrotoxicity in rats. CR was given orally via feeding needle to male Sprague Dawley rats as a single daily dose of 25 or 50 mg/kg for six days...
January 26, 2017: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/28129885/renoprotective-chemical-constituents-from-an-edible-mushroom-pleurotus-cornucopiae-in-cisplatin-induced-nephrotoxicity
#20
Seoung Rak Lee, Dahae Lee, Hae-Jeung Lee, Hyung Jun Noh, Kiwon Jung, Ki Sung Kang, Ki Hyun Kim
Pleurotus cornucopiae (Pleurotaceae) is an edible and medicinal mushroom widely distributed in Korea, China, and Japan. The MeOH extract of the fruiting bodies of P. cornucopiae showed renoprotective effects against cisplatin-induced kidney cell damage. Chemical investigation of the MeOH extract led to the isolation and identification of 12 compounds including noransine (1), uridine (2), uracil (3), (3β, 5α, 6β, 22E, 24S) -ergosta-7, 22-diene-3, 5, 6, 9-tetrol (4), (22E,24S)-ergosta-7,22-diene-3β,5α,6β-triol (5), (22E,24R)-ergosta-8(14),22-diene-3β,5α,6β,7α-tetrol (6), cerebroside B (7), (2R) -N- [(1S, 2R, 3E, 7E) -1- [(β-d-glucopyranosyloxy) methyl] -2-hydroxy-8-methyl-3, 7-heptadecadien-1-yl] -2-hydroxy-heptadecanamide (8), cerebroside D (9), nicotinamide (10), 1,2-bis(hydroxymethyl)-4,5-dimethoxybenzene (11), and benzoic acid (12)...
January 19, 2017: Bioorganic Chemistry
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