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drug-induced nephrotoxicity

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https://www.readbyqxmd.com/read/28714420/evaluation-of-temporal-changes-in-urine-based-metabolomic-and-kidney-injury-markers-to-detect-compound-induced-acute-kidney-tubular-toxicity-in-beagle-dogs
#1
M P Wagoner, Y Yang, J E McDuffie, M Klapczynski, W Buck, L Cheatham, D Eisinger, F Sace, K M Lynch, M Sonee, J-Y Ma, Y Chen, K Marshall, M Damour, L Stephen, Y P Dragan, J Fikes, S Snook, L B Kinter
Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute drug induced kidney injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin-induced kidney lesions in male dogs were characterized by moderate to severe tubular epithelial cell degeneration/necrosis, epithelial cell regeneration and dilation; and a unique urine-based metabolomic fingerprint...
July 13, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/28689766/acute-administration-of-tramadol-and-tapentadol-at-effective-analgesic-and-maximum-tolerated-doses-causes-hepato-and-nephrotoxic-effects-in-wistar-rats
#2
Joana Barbosa, Juliana Faria, Sandra Leal, Luís Pedro Afonso, João Lobo, Odília Queirós, Roxana Moreira, Félix Carvalho, Ricardo Jorge Dinis-Oliveira
Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids...
July 6, 2017: Toxicology
https://www.readbyqxmd.com/read/28689374/identification-of-oat1-oat3-as-contributors-to-cisplatin-toxicity
#3
S Hu, A F Leblanc, A A Gibson, K W Hong, J Y Kim, L J Janke, L Li, A Vasilyeva, D B Finkelstein, J A Sprowl, D H Sweet, E Schlatter, G Ciarimboli, Jhm Schellens, S D Baker, N Pabla, A Sparreboom
Cisplatin is among the most widely used anticancer drugs and known to cause a dose-limiting nephrotoxicity, which is partially dependent on the renal uptake carrier OCT2. We here report a previously unrecognized, OCT2-independent pathway of cisplatin-induced renal injury that is mediated by the organic anion transporters OAT1 and OAT3. Using transporter-deficient mouse models, we found that this mechanism regulates renal uptake of a mercapturic acid metabolite of cisplatin that acts as a precursor of a potent nephrotoxin...
July 8, 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28685136/bilateral-renal-cortical-necrosis-associated-with-smoking-synthetic-cannabinoids
#4
Kanaan Mansoor, Ashley Zawodniak, Tibor Nadasdy, Zeid J Khitan
Synthetic cannabinoids have become a common drug of abuse in recent years and their toxicities have come to light as well. They are known to be notorious for the kidneys, with acute tubular necrosis, acute interstitial nephritis and rhabdomyolysis induced renal injury being the frequent nephrotoxic outcomes in users. We report a case of bilateral renal cortical necrosis, leading to irreversible renal damage and lifelong dialysis dependency.
June 16, 2017: World Journal of Clinical Cases
https://www.readbyqxmd.com/read/28674842/clinical-relevance-and-predictive-value-of-damage-biomarkers-of-drug-induced-kidney-injury
#5
Sandra L Kane-Gill, Pamela L Smithburger, Kianoush Kashani, John A Kellum, Erin Frazee
Nephrotoxin exposure accounts for up to one-fourth of acute kidney injury episodes in hospitalized patients, and the associated consequences are as severe as acute kidney injury due to other etiologies. As the use of nephrotoxic agents represents one of the few modifiable risk factors for acute kidney injury, clinicians must be able to identify patients at high risk for drug-induced kidney injury rapidly. Recently, significant advancements have been made in the field of biomarker utilization for the prediction and detection of acute kidney injury...
July 3, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28670892/age-and-gender-related-renal-side-effects-of-cisplatin-in-animal-model
#6
Zahra Pezeshki, Maryam Maleki, Ardeshir Talebi, Mehdi Nematbakhsh
Backgrounds: Cisplatin (CDDP) is a choice of anti-cancer drug for cancer chemotherapy with serious side effects such as nephrotoxicity. It seems that age is an important factor influencing the side effects of CDDP. This study was designed to determine the role of age and gender simultaneously in CDDP induced renal toxicity. Methods: 40 Wistar male and female rats were assigned as 6 groups in 3 different age categories (10, 16, and 20 weeks old). The single dose of CDDP (7.5 mg/kg, ip) was administrated, and a week later measurements were performed...
June 25, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28670881/ameliorative-effect-of-coenzyme-q10-and-or-candesartan-on-carboplatin-induced-nephrotoxicity-roles-of-apoptosis-transforming-growth-factor-%C3%AE-1-nuclear-factor-kappa-b-and-the-nrf2-ho-1-pathway
#7
Ahmed M Kabel, Abeer A Elkhoely
Background: Carboplatin is a drug that is used for treatment of many types of cancer. However, it may produce serious nephrotoxicity. Candesartan is angiotensin II receptor antagonist employed mainly for control of hypertension. Coenzyme Q10 (CoQ10) is a fat-soluble substance which was proven to have potent antioxidant and anti-inflammatory properties. Aim: Our aim was to study the effects of candesartan and/or CoQ10 on carboplatin-induced nephrotoxicity in mice. Methods: Sixty mice were divided into 6 equal groups: Control untreated; carboplatin; carboplatin + candesartan; carboplatin + CoQ10; carboplatin + carboxymethyl cellulose; and carboplatin + candesartan + CoQ10 group...
June 25, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28670523/evaluation-of-the-protective-effect-of-hydro-alcoholic-extract-of-raspberry-fruit-on-aquaporin1-expression-in-rats-kidney-treated-by-methotrexate
#8
Saeideh Khoshnoud, Homa Mohseni Kouchesfahani, Mohammad Nabiuni
OBJECTIVE: Methotrexate (MTX) is an antimetabolite drug commonly prescribed for the various cancers and autoimmune diseases. Despite its considerable therapeutic effects, nephrotoxicity is the most important side-effect of treatment with MTX. Aquaporin1 (AQP1) is a water channel proteins which is present in mammalian kidney. Raspberry fruit with antioxidant properties is able to protect biological systems from the harmful effects of free radicals. The purpose of this study was to investigate the effect of raspberry extract on expression of AQP1 and the MTX-induced nephrotoxicity in rats...
July 2017: Cell Journal
https://www.readbyqxmd.com/read/28669851/differential-effect-of-quercetin-on-cisplatin-induced-toxicity-in-kidney-and-tumor-tissues
#9
Penélope D Sánchez-González, Francisco J López-Hernández, Montserrat Dueñas, Marta Prieto, Elsa Sánchez-López, Jürgen Thomale, Marta Ruiz-Ortega, José M López-Novoa, Ana I Morales
Strategies to minimize the nephrotoxicity of platinated antineoplastics without affecting its antitumour efficacy are strongly necessary to improve the pharmacotoxicological profile of these drugs. The natural flavonoid quercetin has been shown to afford nephroprotection without affecting cisplatin antitumour effect. The purpose of the present study has been to assess the differential mechanisms of action of cisplatin and quercetin on kidney and tumour tissues that could explain these effects. Wistar rats bearing subcutaneous tumours were treated with cisplatin and quercetin (and the appropriate controls)...
June 30, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28668652/an-integrative-investigation-of-the-toxicity-of-aconiti-kusnezoffii-radix-and-the-attenuation-effect-of-its-processed-drug-using-a-uhplc-q-tof-based-rat-serum-and-urine-metabolomics-strategy
#10
Zhenyu Sui, Qing Li, Lin Zhu, Zhenru Wang, Chunxiao Lv, Ran Liu, Huarong Xu, Bosai He, Zuojing Li, Kaishun Bi
Aconiti kusnezoffii radix (AKR), the root of Aconitum kusnezoffii Reichb., is commonly used in the treatment of the rheumatoid arthritis. However, the clinical application is limited due to its potential toxicity. Therefore, to investigate the mechanism of its potential neurotoxicity and nephrotoxicity, a comprehensive metabolomics study combined with serum biochemistry and histopathology measurements was carried out. A UHPLC-Q-TOF mass spectrometry based metabolomics approach was applied to characterize the AKR toxicity, while the toxicity attenuation effects of Aconiti kusnezoffii radix cocta (AKRC) on Wistar rats were also investigated...
June 21, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28668297/conductive-polymer-based-bioelectrochemical-assembly-for-in-vitro-cytotoxicity-evaluation-renoprotective-assessment-of-salvia-officinalis-against-carbon-tetrachloride-induced-nephrotoxicity
#11
Evangelia Flampouri, Νefeli-Sofia D Sotiropoulou, Sofia Mavrikou, Akrivi-Chara Mouzaki-Paxinou, Petros A Tarantilis, Spyridon Kintzios
BACKGROUND: The rise of organic electronics represents one of the most prominent technological developments of the last two decades, with its interface with biological systems highlighting new directions of research. The "soft" nature of conducting polymers renders them unique platforms for cell-based microdevices, allowing their implementation in drug discovery, pharmaceutical effect analysis, environmental pollutant testing etc. METHODS: Cellular adhesion, proliferation and viability experiments were carried out to verify the biocompatibility of a PEDOT conductive polymer surface...
June 28, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28658959/vitamin-c-attenuates-methotrexate-induced-oxidative-stress-in-kidney-and-liver-of-rats
#12
M Savran, E Cicek, D K Doguc, H Asci, S Yesilot, I A Candan, B Dagdeviren, F N Cankara, M Oncu, A C Uğuz, M K Ozer
Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups...
June 29, 2017: Physiology International
https://www.readbyqxmd.com/read/28653934/evaluation-of-nephroprotective-activity-of-musa-paradisiaca-l-in-gentamicin-induced-nephrotoxicity
#13
Khizar Abbas, Ghazala H Rizwani, Hina Zahid, M Imran Qadir
The objective of the study was to investigate the nephroprotective activity of methanolic extract of different morphological parts (bract, flower, trachea and tracheal fluid) of Musa paradisiaca L. (Family: Musaceae) against gentamicin-induced nephrotoxicity in mice. Gentamicin produced significant changes in biochemical (increased levels of blood urea nitrogen level, blood urea, and serum creatinine), and histological parameters in mice. Treatment with methanolic extract of bract (100 and 250mg/kg, b.w) and flowering stalk (trachea) (250 and 500mg/kg, b...
May 2017: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28652884/drug-absorption-related-nephrotoxicity-assessment-on-an-intestine-kidney-chip
#14
Zhongyu Li, Wentao Su, Yujuan Zhu, Tingting Tao, Dong Li, Xiaojun Peng, Jianhua Qin
Drug absorption in the intestine is tightly related to drug-induced nephrotoxicity, which is a relatively common side effect in clinical practice. It highlights a great need to develop predictive models with high accuracy in the early stage during new drug discovery and development. Herein, we presented a novel intestine-kidney chip, which recapitulated drug absorption in the intestine and its resultant drug toxicity on the kidney. This work aims to provide an integrated tool for accurate assessment of drug absorption-related nephrotoxicity in vitro...
May 2017: Biomicrofluidics
https://www.readbyqxmd.com/read/28650422/the-effects-of-valsartan-on-renal-klotho-expression-and-oxidative-stress-in-alleviation-of-cyclosporine-nephrotoxicity
#15
Sina Raeisi, Amir Ghorbanihaghjo, Hassan Argani, Siavoush Dastmalchi, Babollah Ghasemi, Teimour Ghazizadeh, Nadereh Rashtchizadeh, Mahboob Nemati, Mehran Mesgari Abbasi, Nasrin Bargahi, Hossein Samadi Kafil, Amir Mansour Vatankhah
BACKGROUND: Nephrotoxicity side effect of the immunosuppressive drug, cyclosporine A (CsA), can be a major issue in transplantation medicine. Cyclosporine A-induced nephrotoxicity is multifactorial but oxidative stress has a critical role in this process. It has been demonstrated that Valsartan (Val) as an angiotensin receptor blocker has renoprotective effects, but the molecular mechanisms responsible for the renal protection, independent from its blood pressure lowering effect, have not yet been fully understood...
June 23, 2017: Transplantation
https://www.readbyqxmd.com/read/28640195/pharmacogenomic-variants-may-influence-the-urinary-excretion-of-novel-kidney-injury-biomarkers-in-patients-receiving-cisplatin
#16
Cara Chang, Yichun Hu, Susan L Hogan, Nickie Mercke, Madeleine Gomez, Cindy O'Bryant, Daniel W Bowles, Blessy George, Xia Wen, Lauren M Aleksunes, Melanie S Joy
Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1)...
June 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28636017/effect-of-cisplatin-on-the-transport-activity-of-pii-type-atpases
#17
Francesco Tadini-Buoninsegni, Giacomo Sordi, Serena Smeazzetto, Giovanni Natile, Fabio Arnesano
Cisplatin (cis-diamminedichlorido-Pt(ii)) is extensively used as a chemotherapeutic agent against various types of tumors. However, cisplatin administration causes serious side effects, including nephrotoxicity, ototoxicity and neurotoxicity. It has been shown that cisplatin can interact with P-type ATPases, e.g., Cu(+)-ATPases (ATP7A and ATP7B) and Na(+),K(+)-ATPase. Cisplatin-induced inhibition of Na(+),K(+)-ATPase has been related to the nephrotoxic effect of the drug. To investigate the inhibitory effects of cisplatin on the pumping activity of PII-type ATPases, electrical measurements were performed on sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and Na(+),K(+)-ATPase embedded in vesicles/membrane fragments adsorbed on a solid-supported membrane...
June 21, 2017: Metallomics: Integrated Biometal Science
https://www.readbyqxmd.com/read/28632894/flavonoids-as-modulators-of-metabolic-enzymes-and-drug-transporters
#18
REVIEW
Anca Miron, Ana Clara Aprotosoaie, Adriana Trifan, Jianbo Xiao
Flavonoids, natural compounds found in plants and in plant-derived foods and beverages, have been extensively studied with regard to their capacity to modulate metabolic enzymes and drug transporters. In vitro, flavonoids predominantly inhibit the major phase I drug-metabolizing enzyme CYP450 3A4 and the enzymes responsible for the bioactivation of procarcinogens (CYP1 enzymes) and upregulate the enzymes involved in carcinogen detoxification (UDP-glucuronosyltransferases, glutathione S-transferases (GSTs))...
June 2017: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/28629150/role-of-nigella-sativa-and-its-constituent-thymoquinone-on-chemotherapy-induced-nephrotoxicity-evidences-from-experimental-animal-studies
#19
REVIEW
Marco Cascella, Giuseppe Palma, Antonio Barbieri, Sabrina Bimonte, Nagoth Joseph Amruthraj, Maria Rosaria Muzio, Vitale Del Vecchio, Domenica Rea, Michela Falco, Antonio Luciano, Claudio Arra, Arturo Cuomo
BACKGROUND: Most chemotherapeutic drugs are known to cause nephrotoxicity. Therefore, new strategies have been considered to prevent chemotherapy-induced nephrotoxicity. It is of note that Nigella sativa (NS), or its isolated compound Thymoquinone (TQ), has a potential role in combating chemotherapy-induced nephrotoxicity. AIM: To analyze and report the outcome of experimental animal studies on the protective effects of NS/TQ on chemotherapy-associated kidney complications...
June 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28618760/changes-in-the-serum-liver-and-renal-cortical-lipids-and-electrolytes-in-rabbits-with-cisplatin-induced-nephrotoxicity
#20
Abdelgayoum Ahmed Abdel-Gayoum, Mohamed Hamza Sulaiman Ahmida
BACKGROUND/AIM: Cisplatin is an anticancer drug that can induce nephrotoxicity. Its toxicity is associated with dyslipidemia and disturbed electrolyte balance. In the present study we investigated the changes in serum lipid profile and electrolyte levels and their contents in kidney and liver tissues of rabbits treated with cisplatin. MATERIALS AND METHODS: Twenty-eight adult male New Zealand White rabbits were used in the experiment. Animals of groups C, P1, and P2 were injected with saline, cisplatin (4...
June 12, 2017: Turkish Journal of Medical Sciences
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