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drug-induced nephrotoxicity

Hassan Izzedine
Drug-induced nephrotoxicity (DIN) remains a current problem with economic and medical consequences. It affects all nephron segments. Recovery of renal function is based on the identification of risk factors, early diagnosis of renal disease, rapid (if possible) cessation of the causative agent and, in some cases, adjunctive therapy. Prevention is based on identification of early markers of DIN, correction of risk factors, initial assessment of renal function for adequate dosage adjustment and exclusion of other nephrotoxic factors...
March 11, 2018: Néphrologie & Thérapeutique
Haesol Lee, Dahae Lee, Ki Sung Kang, Ji Hoon Song, You-Kyoung Choi
Cisplatin is a well-known anticancer drug frequently used for treating solid tumors, including ovarian, testicular, bladder, and cervical tumors. However, usage of cisplatin has been limited because of its adverse effects, particularly nephrotoxicity. Therefore, the present study sought to investigate the protective effect of formononetin against cisplatin-induced cytotoxicity in LLC-PK1 pig kidney epithelial cells as well as the anticancer effect of cisplatin in three different human cervical cancer cell lines, including HeLa, SiHa, and CaSKi cells...
March 12, 2018: International Journal of Molecular Sciences
Simin Dashti-Khavidaki, Hossein Khalili, Mohsen Nasiri-Toosi
There was no report of nephrotoxicity during clinical trials assessed sofosbuvir for treatment of hepatitis C (HCV) infection. This may be due to excluding patients with severe kidney dysfunction, as a main population at risk for drug-induced nephrotoxicity from these studies. There are some reports of acute kidney injury (AKI) possibly related to sofosbuvir-containing treatments from real-life experiences. Areas covered: Available data on epidemiology, type, and possible risk factors for nephrotoxicity of sofosbuvir-containing treatment are reviewed...
March 14, 2018: Expert Review of Clinical Pharmacology
Jeonghwan Lee, Sejoong Kim
The kidneys play a pivotal role in most drug-removal processes and are important when evaluating drug safety. Kidney dysfunction resulting from various drugs is an important issue in clinical practice and during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and animals, and static cell culture experiments cannot fully reflect the actual microphysiological environment in humans...
March 8, 2018: Current Drug Metabolism
Tom Tg Nieskens, Janny Gp Peters, Dina Dabaghie, Daphne Korte, Katja Jansen, Alexander H Van Asbeck, Neslihan N Tavraz, Thomas Friedrich, Frans Russel, Rosalinde Masereeuw, Martijn J Wilmer
Cisplatin is a cytostatic drug used for treatment of solid organ tumors. The main adverse effect is organic cation transporter 2 (OCT2)-mediated nephrotoxicity, observed in 30% of patients. The contribution of other renal drug transporters is elusive. Here, cisplatin-induced toxicity was evaluated in human-derived proximal tubule epithelial cells (ciPTEC) expressing renal drug transporters, including OCT2 and organic anion transporter 1 (OAT1) or 3 (OAT3). Parent ciPTEC demonstrated OCT2-dependent cisplatin toxicity (TC50 34±1 μM after 24 h exposure), as determined by cell viability...
March 7, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Hisato Shima, Manabu Tashiro, Satoshi Yamada, Motokazu Matsuura, Kazuyoshi Okada, Toshio Doi, Jun Minakuchi, Shu Kawashima
BACKGROUND: Cilostazol is an antiplatelet drug that is widely prescribed for the prevention of secondary stroke. Adverse reactions to cilostazol include headaches, palpitations, and diarrhea. Little is known about the nephrotoxicity of cilostazol, such as acute kidney injury. We report a biopsy-proven case of diffuse tubulointerstitial nephritis induced by cilostazol. CASE PRESENTATION: A 69-year-old woman prescribed cilostazol was hospitalized for acute kidney injury...
March 5, 2018: BMC Nephrology
Karen Steindorf, Martina E Schmidt, Philipp Zimmer
A growing number of literature reports positive effects of physical activity and exercise. These effects concern prevention, mortality and progress of cancer. Furthermore they show a reduction of disease- and treatment-specific side effects, which implies a better patients' quality of life. Evidence shows a decreased mortality risk in patients with physically active cancer of colon, breast, ovaries and prostate. Activity recommendations for patients with cancer do not differ from those for healthy persons...
March 2018: Deutsche Medizinische Wochenschrift
Simon Lagies, Roman Pichler, Michael M Kaminski, Manuel Schlimpert, Gerd Walz, Soeren S Lienkamp, Bernd Kammerer
Fibroblasts can be directly reprogrammed to induced renal tubular epithelial cells (iRECs) using four transcription factors. These engineered cells may be used for disease modeling, cell replacement therapy or drug and toxicity testing. Direct reprogramming induces drastic changes in the transcriptional landscape, protein expression, morphological and functional properties of cells. However, how the metabolome is changed by reprogramming and to what degree it resembles the target cell type remains unknown. Using untargeted gas chromatography-mass spectrometry (GC-MS) and targeted liquid chromatography-MS, we characterized the metabolome of mouse embryonic fibroblasts (MEFs), iRECs, mIMCD-3 cells, and whole kidneys...
March 1, 2018: Scientific Reports
M S Chowdhury, S K Saha, E O Eva, M M Sarker
An experimental study was carried out to evaluate the effect of Captopril on Gentamicin induced nephrotoxicity in rats in the Department of Pharmacology, Mymensingh Medical College and Dhaka Medical College, Bangladesh. Gentamicin antibiotic is most commonly employed clinically because of their potent bactericidal activities against Gram negative bacterial infections, less bacterial resistance, post-antibiotic effects and low cost. Gentamicin is associated with an induction of slow rises in serum creatinine, inflammation and perivascular edema, tubular degeneration and necrosis, tubular debris collection, glomerular atrophy which ultimately show the way to renal dysfunction...
January 2018: Mymensingh Medical Journal: MMJ
Sara Hosseinian, Mousa-Al-Reza Hadjzadeh, Noma Mohamadian Roshan, Majid Khazaei, Samira Shahraki, Reza Mohebbati, Abolfazl Khajavi Rad
Cisplatin is one of the important antineoplastic drugs. Its clinical use has been restricted due to severe kidney toxicity. Nigella sativa (N. sativa) is an herbaceous plant with many pharmacologic effects. In the present study, we evaluated the protective effects of aqueous-ethanolic extract of N. sativa and Vitamin E on cisplatin-induced nephrotoxicity in rats. Eighty male rats were divided into eight groups: control, cisplatin (6 mg/kg; ip), preventive Vitamin E (100 mg/kg), preventive N. sativa (100,200 mg/kg), preventive + treatment Vitamin E, and preventive + treatment N...
January 2018: Saudi Journal of Kidney Diseases and Transplantation
Yuling Tong, Xitong Huang, Mi Lu, Bo-Yang Yu, Jiangwei Tian
The development of well-designed nanoprobes for specific imaging of multiple biomarkers in renal cells will afford beneficial information related to the transmutation process of drug-induced kidney injury (DIKI). However, the most reported nanoprobes for DIKI detection were dependent on single-signal output and lack of kidney targeting. In this work, we reported a renal cell targeting and dual-signal nanoprobe by encapsulating Brite 670 and Dabcyl-KFFFDEVDK-FAM into low molecular weight chitosan nanoparticle...
February 14, 2018: Analytical Chemistry
Isiaka Ayofe Adekunle, Christian Eseigbe Imafidon, Ayowole Abraham Oladele, Abiodun Oladele Ayoka
Cyclosporine (CYA), a common immuno-suppressant drug that is used in organ transplants, is associated with nephrotoxic effects. Scientific exploration of natural products of plant origin should be considered; especially, in a world with increasing prevalence of kidney diseases. Effects of ginger polyphenols (GP) in Wistar rats with CYA-induced perturbations in electrolyte balance and kidney function was determined. Fifty Wistar rats were recruited for this study such that graded doses of GP were administered following CYA-induced kidney injury and comparisons were made against control and toxic groups at p < 0...
February 7, 2018: Pathophysiology: the Official Journal of the International Society for Pathophysiology
Quadri Kunle Alabi, Rufus Ojo Akomolafe, Olaoluwa Sesan Olukiran, Aliyat Olajumoke Nafiu, Modinat Adebukola Adefisayo, Olurotimi Isaac Owotomo, Joseph Gbenga Omole, Kehinde Peace Olamilosoye
OBJECTIVES: Cisplatin (CIS) is an effective antitumor drug. However, its clinical use is limited due to nephrotoxicity. l-Carnitine and vitamin C are both natural antioxidant that can be obtained from diets. This study investigated the effects of l-carnitine and/or vitamin C in rats against cisplatin-induced nephrotoxicity. METHODS: Twenty-five male Wistar rats were divided into 5 groups of 5 rats each. Group 1, normal control. Group 2, positive control, received cisplatin (10 mg/kg/day intraperitoneally [i...
February 9, 2018: Journal of the American College of Nutrition
Yan-Zi Li, Shen Ren, Xiao-Tong Yan, Yin-Shi Sun, Hui-Ping Li, Wei Li, Ying-Ying Liu, Zi Wang
ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (Turcz.) Baill (S. chinensis) is a frequently used traditional Chinese medicine, and modern pharmacological research has proven that S. chinensis has antioxidant, anti-hepatotox, anti-inflammatory, and anti-nephrotoxic effects. Cisplatin is widely used as antineoplastic drug at presenteffects, but the clinical application of cisplatin is limitedowing to nephrotoxicity. AIM OF THE STUDY: To demonstrate the renoprotective activity of the extract of the stems of Schisandra chinensis (SCE) in model mice established by cisplatin triggering acute kidney injury (AKI)...
February 5, 2018: Journal of Ethnopharmacology
Xu Cao, Xiaowei Nie, Siping Xiong, Lei Cao, Zhiyuan Wu, Philip K Moore, Jin-Song Bian
Cisplatin is a major chemotherapeutic drug for solid tumors whereas it may lead to severe nephrotoxicity. Despite decades of efforts, effective therapies remain largely lacking for this disease. In the current research, we investigated the therapeutic effect of hydrogen polysulfide, a novel hydrogen sulfide (H2S) derived signaling molecule, in cisplatin nephrotoxicity and the mechanisms involved. Our results showed that polysulfide donor Na2S4 ameliorated cisplatin-caused renal toxicity in vitro and in vivo through suppressing intracellular reactive oxygen species (ROS) generation and downstream mitogen-activated protein kinases (MAPKs) activation...
February 1, 2018: Redox Biology
Fanghua Li, Zhiwen Liu, Chengyuan Tang, Juan Cai, Zheng Dong
Cisplatin, a widely used cancer therapy drug, induces nephrotoxicity or acute kidney injury (AKI), but the underlying mechanism remains unclear, and renal protective approaches are not available. Fibroblast growth factor (FGF)21 is an endocrine factor that regulates glucose uptake, metabolism, and energy expenditure. However, recent work has also implicated FGF21 in cellular stress response under pathogenic conditions. The role and regulation of FGF21 in AKI are unclear. Here, we show that FGF21 was dramatically induced during cisplatin treatment of renal tubular cells in vitro and mouse kidneys in vivo...
January 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Supakanya Wongrakpanich, Amaraporn Wongrakpanich, Katie Melhado, Janani Rangaswami
NSAIDs, non-steroidal anti-inflammatory drugs, are one of the most commonly prescribed pain medications. It is a highly effective drug class for pain and inflammation; however, NSAIDs are known for multiple adverse effects, including gastrointestinal bleeding, cardiovascular side effects, and NSAID induced nephrotoxicity. As our society ages, it is crucial to have comprehensive knowledge of this class of medication in the elderly population. Therefore, we reviewed the pharmacodynamics and pharmacokinetics, current guidelines for NSAIDs use, adverse effect profile, and drug interaction of NSAIDs and commonly used medications in the elderly...
February 2018: Aging and Disease
Gen Kanayama, Marc J Kaufman, Harrison G Pope
PURPOSE OF REVIEW: To summarize recent findings regarding the public health impact of androgen abuse. RECENT FINDINGS: Abuse of androgens (also called 'anabolic-androgenic steroids') has grown into a major worldwide substance abuse problem involving tens of millions of individuals, of whom about 98% are men. Most androgen abusers are still under age 50 today, and thus, the long-term effects of these drugs are only beginning to be understood. Recent studies confirm that long-term supraphysiologic androgen exposure produces cardiovascular toxicity, characterized especially by cardiomyopathy and atherosclerotic disease...
January 24, 2018: Current Opinion in Endocrinology, Diabetes, and Obesity
Cyrille Vandenbussche, Cynthia Van der Hauwaert, Edmone Dewaeles, Jessica Franczak, Marie-Flore Hennino, Viviane Gnemmi, Grégoire Savary, Quentin Tavernier, Nicolas Nottet, Agnès Paquet, Michaël Perrais, David Blum, Bernard Mari, Nicolas Pottier, François Glowacki, Christelle Cauffiez
Although Tacrolimus is an immunosuppressive drug widely used in renal transplantation, its chronic use paradoxically induces nephrotoxic effects, in particular renal fibrosis, which is responsible for chronic allograft dysfunction and represents a major prognostic factor of allograft survival. As molecular pathways and mechanisms involved in Tacrolimus-induced fibrogenic response are poorly elucidated, we assessed whether miRNAs are involved in the nephrotoxic effects mediated by Tacrolimus. Treatment of CD-1 mice with Tacrolimus (1 mg/kg/d for 28 days) resulted in kidney injury and was associated with alteration of a gene expression signature associated with cellular stress, fibrosis and inflammation...
January 23, 2018: Archives of Toxicology
Zumrut Sahbudak Bal, Fulya Kamit Can, Pinar Yazici, Ayse Berna Anil, Muhterem Duyu, Dilek Yilmaz Ciftdogan, Ozkalay Nisel Yilmaz, Feriha Cilli, Bulent Karapinar
Colistin, an old cationic polypeptide antibiotic, have been reused due to rising incidence of infections caused by multi-drug resistant (MDR) Gram-negative microorganisms and the lack of new antibiotics. Therefore, we evaluated safety and efficacy of colistin in treatment of these infections. This study included 104 critically ill children with a median age of 55,9 months between January 2011 and January 2016. Nephrotoxicity occurred in 11 (10.5%) patients. Nephrotoxicity occurred between the third and seventh day of treatment in 63% of colistin induced nephrotoxicity episodes...
January 17, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
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