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drug-induced nephrotoxicity

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https://www.readbyqxmd.com/read/28421385/in-vitro-and-in-vivo-anti-tumor-effects-of-selected-platinum-iv-and-dinuclear-platinum-ii-complexes-against-lung-cancer-cells
#1
Milos Arsenijevic, Marija Milovanovic, Snezana Jovanovic, Natalija Arsenijevic, Bojana Simovic Markovic, Marina Gazdic, Vladislav Volarevic
In the present study, cytotoxic effects of cisplatin, the most usually used chemotherapeutic agent, were compared with new designed platinum(IV) ([PtCl4(en)] (en = ethylenediamine) and [PtCl4(dach)]) (dach = (±)-trans-1,2-diaminocyclohexane) and platinum(II) complexes ([{trans-Pt(NH3)2Cl}2(μ-pyrazine)](ClO4)2 (Pt1), [{trans-Pt(NH3)2Cl}2(μ-4,4'-bipyridyl)](ClO4)2DMF(Pt2),[{trans-Pt(NH3)2Cl}2(μ-1,2-bis(4pyridyl)ethane)](ClO4)2 (Pt3)), in vitro and in vivo against human and murine lung cancer cells, to determine anti-tumor potential of newly synthesized platinum-based drugs in the therapy of lung cancer...
April 18, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28414026/targeting-oct2-and-p53-formononetin-prevents-cisplatin-induced-acute-kidney-injury
#2
Di Huang, Chuangyuan Wang, Yingjie Duan, Qiang Meng, Zhihao Liu, Xiaokui Huo, Huijun Sun, Xiaodong Ma, Kexin Liu
Nephrotoxicity is one of major side effects of cisplatin in chemotherapy. Therefore, there is an urgent medical need to develop drugs that may protect kidney from toxicity. In previous study, we found that it showed the protective effects of formononetin against apoptosis by upregulating Nrf2. In this study, we investigated the renoprotective effect of formononetin against cisplatin-induced AKI and tried to elucidate the possible mechanisms. The amelioration of renal function, histopathological changes, and apoptosis in tubular cells was observed after formononetin treatment...
April 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28409500/tissue-protective-activity-of-selenomethionine-and-d-panthetine-in-b16-melanoma-bearing-mice-under-doxorubicin-treatment-is-not-connected-with-their-ros-scavenging-potential
#3
Rostyslav R Panchuk, Nadia R Skorokhyd, Yuliya S Kozak, Liliya V Lehka, Andrey G Moiseenok, Rostyslav S Stoika
AIM: To evaluate molecular mechanisms of tissue-protective effects of antioxidants selenomethionine (SeMet) and D-pantethine (D-Pt) applied in combination with doxorubicin (Dx) in B16 melanoma-bearing-mice. METHODS: Impact of the chemotherapy scheme on a survival of tumor-bearing animals, general nephro- and hepatotoxicity, blood cell profile in vivo, and ROS content in B16 melanoma cells in vitro was compared with the action of Dx applied alone. Nephrotoxicity of the drugs was evaluated by measuring creatinine indicator assay, hepatotoxicity was studied by measuring the activity of ALT/AST enzymes, and myelotoxicity was assessed by light microscopic analysis of blood smears...
April 14, 2017: Croatian Medical Journal
https://www.readbyqxmd.com/read/28403627/resolution-of-tenofovir-disoproxil-fumarate-induced-fanconi-syndrome-with-switch-to-tenofovir-alafenamide-fumarate-in-a-hiv-1-and-hepatitis-b-co-infected-patient
#4
Maile Karris
Fanconi syndrome is a rare adverse effect of tenfovir disoproxil fumarate (TDF) (1). Tenofovir alafenamide fumarate (TAF) is a novel pro-drug with less nephrotoxicity. We report resolution of Fanconi syndrome in a HIV and hepatitis B co-infected patient switched from TDF to TAF.
April 13, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28393561/hsp72-is-an-early-biomarker-to-detect-cisplatin-and-acetaminophen-nephrotoxicity
#5
Rosalba Pérez-Villalva, Jonatan Barrera-Chimal, Juan Carlos Aguilar-Carrasco, Ixchel Lima-Posada, Cristino Cruz, Victoria Ramirez, Yvett González-Bobadilla, Norma Uribe, Laura Trumper, Norma A Bobadilla
OBJECTIVE: To evaluate whether the urinary HSP72 levels (uHSP72) are a useful biomarker for early diagnosis of AKI induced by two widely used drugs: cisplatin and acetaminophen. MATERIALS AND METHODS: To analyze the time-course of nephrotoxic injury and uHSP72 levels, male Wistar rats were administered a single high dose of cisplatin (7-mg/kg) or acetaminophen (750- mg/kg) and were assessed at 6, 12, 24, 48, 72, 96 and 120-h. RESULTS: AKI induced by cisplatin was characterized by tubular injury that started at 6-h and was enhanced 48-h after...
April 10, 2017: Biomarkers: Biochemical Indicators of Exposure, Response, and Susceptibility to Chemicals
https://www.readbyqxmd.com/read/28386348/inhibition-of-cox-2-pge2-cascade-ameliorates-cisplatin-induced-mesangial-cell-apoptosis
#6
Xiaowen Yu, Yunwen Yang, Hui Yuan, Meng Wu, Shuzhen Li, Wei Gong, Jing Yu, Weiwei Xia, Yue Zhang, Guixia Ding, Songming Huang, Zhanjun Jia, Aihua Zhang
Cisplatin is one of the most potent cytotoxic drug for the treatment of many types of cancer. However, the side effects on normal tissues, particularly on the kidney, greatly limited its use in clinic. Emerging evidence demonstrated that cisplatin could directly cause mesangial cell apoptosis, while the potential mechanism is still elusive. Here we examined the contribution of COX-2 in cisplatin-induced mesangial cell apoptosis. Firstly, we found cisplatin induced cell apoptosis in mesangial cells shown by increased number of apoptotic cells in parallel with the upregulation of Bax and the downregulation of Bcl-2...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28384101/novel-therapeutic-approaches-of-natural-oil-from-black-seeds-and-its-underlying-mechanisms-against-kidney-dysfunctions-in-haloperidol-induced-male-rats
#7
Jacob K Akintunde, Opeyemi K Abubakar
BACKGROUND: Antipsychotic drugs could be nephrotoxic in schizophrenia patients. METHODS: The present study investigated the protective effect of oil from black seed on kidney dysfunctions using several biological approaches in adult rats. The animals were divided into six groups (n=10): normal control rats; haloperidol (HAL)-induced rats: induced rats were pre-, co- and post-treated with black seed oil (BSO), respectively, and the last group was treated with the oil only...
April 6, 2017: Drug Metabolism and Personalized Therapy
https://www.readbyqxmd.com/read/28372552/the-6r-s-of-drug-induced-nephrotoxicity
#8
REVIEW
Linda Awdishu, Ravindra L Mehta
Drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. Our current knowledge of drug induced kidney disease is limited due to varying definitions of kidney injury, incomplete assessment of concurrent risk factors and lack of long term outcome reporting. Electronic surveillance presents a powerful tool to identify susceptible populations, improve recognition of events and provide decision support on preventative strategies or early intervention in the case of injury...
April 3, 2017: BMC Nephrology
https://www.readbyqxmd.com/read/28372472/in-vitro-study-of-putative-genomic-biomarkers-of-nephrotoxicity-through-differential-gene-expression-using-gentamicin
#9
Sarah Cristina Teixeira Silva, Leonardo Augusto de Almeida, Stellamaris Soares, Marina Felipe Grossi, Anete Maria Santana Valente, Carlos Alberto Tagliati
Drug-induced nephrotoxicity is one of the most frequently observed effects in long-term pharmacotherapy. The effects of nephrotoxicity are commonly discovered later due to a lack of sensitivity in in vivo methods. Therefore, researchers have tried to develop in vitro alternative methods for early identification of toxicity. In this study, LLC-PK1 cells were exposed to gentamicin through MTT and trypan blue assay. Concentrations of 4 (low), 8 (medium), and 12 (high) mM, were used to evaluate differential gene expression...
April 3, 2017: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/28356716/synergistic-protective-effect-of-n-acetylcysteine-and-taurine-against-cisplatin-induced-nephrotoxicity-in-rats
#10
Wessam M Abdel-Wahab, Farouzia I Moussa, Najwa A Saad
Cisplatin (cis-diaminedichloroplatinum II; CDDP) is an effective anticancer drug, but it has limitations because of its nephrotoxicity. This study investigates the protective effect of N-acetylcysteine (NAC) and taurine (TAU), both individually and in combination, against CDDP nephrotoxicity in rats. For this purpose, 48 male rats were assigned into eight groups (n=6) as follows: 1) control group, 2) NAC group, 3) TAU group, 4) NAC-TAU group, 5) CDDP group, 6) CDDP-NAC group, 7) CDDP-TAU group, and 8) CDDP-NAC-TAU group...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28348914/brincidofovir-use-after-foscarnet-crystal-nephropathy-in-a-kidney-transplant-recipient-with-multiresistant-cytomegalovirus-infection
#11
Romain Vial, Christine Zandotti, Sophie Alain, Alexandre Decourt, Noémie Jourde-Chiche, Raj Purgus, Charleric Bornet, Laurent Daniel, Valérie Moal, Tristan Legris
Background. Cytomegalovirus (CMV) antiviral drug resistance constitutes an increasing challenge in transplantation. Foscarnet is usually proposed when resistance for ganciclovir is suspected, but its use is limited by its nephrotoxicity. Case Presentation. We report a case of multiresistant CMV disease in a kidney transplant recipient. Foscarnet was prescribed after ganciclovir treatment failure in a patient with two mutations in the UL97 viral gene. Foscarnet induced biopsy-proven kidney crystal precipitation that resulted in severe acute transplant failure and nephrotic syndrome...
2017: Case Reports in Transplantation
https://www.readbyqxmd.com/read/28340076/cisplatin-induced-renal-inflammation-is-ameliorated-by-cilastatin-nephroprotection
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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