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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/28339935/nephrotoxicity-of-anticancer-treatment
#2
Jolanta Malyszko, Klaudia Kozlowska, Leszek Kozlowski, Jacek Malyszko
Severe adverse systemic drug events occur commonly as a result of treatment of cancer patients. Nephrotoxicity of chemotherapeutic agents remains a significant complication limiting the efficacy of the treatment. A variety of renal disease and electrolyte disorders can result from the drugs that are used to treat malignant disease. The kidneys are a major elimination pathway for many antineoplastic drugs and their metabolites. Tumour lysis syndrome, an emergency in haematooncology, occurs most often after the initiation of cytotoxic therapy in patients with high-grade lymphomas and acute lymphoblastic leukaemia...
October 6, 2016: Nephrology, Dialysis, Transplantation
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 the present 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/28314361/hepatotoxicity-and-drug-chemical-interaction-toxicity-of-nanoclay-particles-in-mice
#7
Katsuhiro Isoda, Ryutaro Nagata, Tomoya Hasegawa, Yuichiro Taira, Ikuko Taira, Yoshimi Shimizu, Kazuo Isama, Tetsuji Nishimura, Isao Ishida
Nanomaterials are relatively new and unconventional materials with many useful properties, but their effects on biological systems are poorly understood. Nanoclay is a general term for layered mineral silicate nanoparticles that are ideally suited for use in clay-based nanocomposites. The potential biological hazards of nanoclays have not been addressed, however. Therefore, we investigated the in vivo effects and drug interactions of nanoclays. In mice, administration of nanoclay particles via the tail vein led to acute liver injury...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28303105/caloric-restriction-is-more-efficient-than-physical-exercise-to-protect-from-cisplatin-nephrotoxicity-via-ppar-alpha-activation
#8
Gabriel R Estrela, Frederick Wasinski, Rogério O Batista, Meire I Hiyane, Raphael J F Felizardo, Flavia Cunha, Danilo C de Almeida, Denise M A C Malheiros, Niels O S Câmara, Carlos C Barros, Michael Bader, Ronaldo C Araujo
The antineoplastic drug cisplatin promotes renal injury, which limits its use. Protocols that reduce renal cisplatin toxicity will allow higher doses to be used in cisplatin treatment. Here, we compare physical exercise and caloric restriction (CR) as protocols to reduce cisplatin renal injury in mice. Male C57BL/6 were divided into four groups: Control, cisplatin, exercise + cisplatin, and 30% CR + cisplatin. Animals were injected with a single dose of cisplatin (20 mg/kg i.p.) and sacrificed 96 h after injection...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28292991/-management-of-kidney-disease-on-cancer-chemotherapy-with-other-drugs-than-platinum-agents
#9
Hideki Shimodaira
"Japanese clinical practice guidelines for the management of kidney disease in cancer survivors"have been published. This guideline recommended several managements for nephrotoxicity of other agents than platinum such as the urinary alkylation during methotrexate administration, suspending of anti-angiogenetic agent for the grade 2 or more proteinuria, dose modification of bisphosphonate based on the renal function. Understanding the background of these recommendations will contribute for safe cancer chemotherapy...
March 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28292990/-nephropathy-in-patients-undergoing-cancer-drug-therapy-platinum-derivatives-cisplatin-and-carboplatin
#10
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/28284383/tubulointerstitial-injury-and-drugs-of-abuse
#11
REVIEW
Arani Nanavati, Leal C Herlitz
Drug abuse is widespread in many populations, and patients abusing illicit substances are at a significantly increased risk of kidney injury. The tubulointerstitial compartment is a common target of these nephrotoxic agents. This review will cover some of the common illicit drugs and will focus on the tubulointerstitial injuries seen in the setting of drug abuse. Agents addressed in this review are synthetic cannabinoids, "bath salts," ecstasy, anabolic steroids, inhaled solvents, heroin, and cocaine. The most frequent biopsy findings are those of acute tubular necrosis and acute interstitial nephritis...
March 2017: Advances in Chronic Kidney Disease
https://www.readbyqxmd.com/read/28284381/mechanisms-of-drug-induced-interstitial-nephritis
#12
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/28280692/influence-of-tacrolimus-metabolism-rate-on-renal-function-after-solid-organ-transplantation
#13
REVIEW
Gerold Thölking, Hans Ulrich Gerth, Katharina Schuette-Nuetgen, Stefan Reuter
The calcineurin inhibitor (CNI) tacrolimus (TAC) is an integral part of the immunosuppressive regimen after solid organ transplantation. Although TAC is very effective in prevention of acute rejection episodes, its highly variable pharmacokinetic and narrow therapeutic window require frequent monitoring of drug levels and dose adjustments. TAC can cause CNI nephrotoxicity even at low blood trough levels (4-6 ng/mL). Thus, other factors besides the TAC trough level might contribute to CNI-related kidney injury...
February 24, 2017: World Journal of Transplantation
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
#14
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/28271897/branched-chain-amino-acids-as-predictors-for-individual-differences-of-cisplatin-nephrotoxicity-in-rats-a-pharmacometabonomics-study
#15
Pei Zhang, Wei Li, Jiaqing Chen, Ruiting Li, Zunjian Zhang, Yin Huang, Fengguo Xu
Nephrotoxicity is the dose-limiting adverse effect of cisplatin with large individual differences. Up to now, little has been done on how to recognize and predict the individual differences in either preclinical or clinical research. In the present study, important postdose indicators were screened out first and integrated into a grouping factor, according to which rats were recognized as lowly or highly sensitive individuals. Then, mass-spectrometry-based untargeted metabolomics approach was performed to dissect the metabolic differences in predose serum of the two groups...
March 17, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28270931/design-and-methods-of-the-pan-canadian-applying-biomarkers-to-minimize-long-term-effects-of-childhood-adolescent-cancer-treatment-able-nephrotoxicity-study-a-prospective-observational-cohort-study
#16
Kelly R McMahon, Shahrad Rod Rassekh, Kirk R Schultz, Maury Pinsk, Tom Blydt-Hansen, Cherry Mammen, Ross T Tsuyuki, Prasad Devarajan, Geoff D E Cuvelier, Lesley G Mitchell, Sylvain Baruchel, Ana Palijan, Bruce C Carleton, Colin J D Ross, Michael Zappitelli
BACKGROUND: Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity...
2017: Canadian Journal of Kidney Health and Disease
https://www.readbyqxmd.com/read/28257038/establishment-of-hk-2-cells-as-a-relevant-model-to-study-tenofovir-induced-cytotoxicity
#17
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/28248714/nebulization-of-antiinfective-agents-in-invasively-mechanically-ventilated-adults-a-systematic-review-and-meta-analysis
#18
Candela Solé-Lleonart, Jean-Jacques Rouby, Stijn Blot, Garyfallia Poulakou, Jean Chastre, Lucy B Palmer, Matteo Bassetti, Charles-Edouard Luyt, Jose M Pereira, Jordi Riera, Tim Felton, Jayesh Dhanani, Tobias Welte, Jose M Garcia-Alamino, Jason A Roberts, Jordi Rello
BACKGROUND: Nebulization of antiinfective agents is a common but unstandardized practice in critically ill patients. METHODS: A systematic review of 1,435 studies was performed in adults receiving invasive mechanical ventilation. Two different administration strategies (adjunctive and substitute) were considered clinically relevant. Inclusion was restricted to studies using jet, ultrasonic, and vibrating-mesh nebulizers. Studies involving children, colonized-but-not-infected adults, and cystic fibrosis patients were excluded...
March 1, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28247443/acute-kidney-injury-in-patients-treated-with-iv-beta-lactam-beta-lactamase-inhibitor-combinations
#19
W Cliff Rutter, David S Burgess
STUDY OBJECTIVE: Increased acute kidney injury (AKI) incidence has been reported in patients receiving piperacillin-tazobactam (PTZ) therapy compared to other beta-lactams. This study sought to determine if the addition of beta-lactamase inhibitors impact AKI incidence by comparing patients treated with PTZ or ampicillin-sulbactam (SAM). DESIGN: Retrospective cohort study. SETTING: Large academic tertiary care hospital. PATIENTS: Overall, 2,448 patients received PTZ (n=1,836) or SAM (n=612) for at least 48 hours between September 1, 2007 and September 30, 2015...
March 1, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28242136/braf-signaling-pathway-inhibition-podocyte-injury-and-nephrotic-syndrome
#20
Luca Perico, Mario Mandalà, Arrigo Schieppati, Camillo Carrara, Paola Rizzo, Sara Conti, Lorena Longaretti, Ariela Benigni, Giuseppe Remuzzi
Dabrafenib and trametinib, BRAF and MEK inhibitors, respectively, are effective targeted metastatic melanoma therapies, but little is known about their nephrotoxicity. Although tubulointerstitial injury has been the most widely reported renal side effect of targeted melanoma therapy, nephrotic syndrome has not been reported before. We report on a patient with metastatic melanoma who developed nephrotic syndrome during dabrafenib and trametinib treatment. Kidney biopsy showed diffuse loss of podocyte cytoarchitecture, extensive foot-process effacement, and glomerular endothelial injury...
February 24, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
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