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Cisplatin ototoxicity

Meng Wei, Xiaojun Yuan
Cisplatin is the principal chemotherapeutic agent and also tremendously increases the survival for pediatric patients with neuroblastoma or hepatoblastoma. With the extended overall survival period, clinical medical workers and parents gradually attach more attention to the late effect of chemotherapy of these children. The purpose of this study is to analyze the incidence and risk factors of cisplatin-based hearing loss. We retrospectively collected the archives of cisplatin-based chemotherapy and audiometric evaluation from 2005 through 2017 at Xinhua Hospital...
August 8, 2018: Journal of Pediatric Hematology/oncology
Robert Alan Hazlitt, Tal Teitz, Justine D Bonga, Jie Fang, Shiyong Diao, Luigi I Iconaru, Lei Yang, Asli N Goktug, Duane G Currier, Taosheng Chen, Zoran Rankovic, Jaeki Min, Jian Zuo
There are currently no FDA-approved therapies to prevent the hearing loss associated with the usage of cisplatin in chemotherapeutic regimens. We recently demonstrated that the pharmacologic inhibition with kenpaullone or genetic deletion of CDK2 preserved hearing function in animal models treated with cisplatin, which suggests that CDK2 is a promising therapeutic target to prevent cisplatin-induced ototoxicity. In this study, we identified two lead compounds, AT7519 and AZD5438, from a focused library screen of 187 CDK2 inhibitors, performed in an immortalized cell line derived from neonatal mouse cochleae treated with cisplatin...
August 9, 2018: Journal of Medicinal Chemistry
Takeshi Ezaki, Shin Nishiumi, Takeshi Azuma, Masaru Yoshida
Cisplatin, which is an inorganic molecule containing a platinum ion, is an antineoplastic agent that has been used to treat various solid tumors. However, its side effects include nephrotoxicity, neurotoxicity, bone marrow toxicity, gastrointestinal toxicity, and ototoxicity, which can limit its use. In this study, nephrotoxicity was caused by the intraperitoneal injection of cisplatin into rats, and then metabolome analysis was performed using gas chromatography/mass spectrometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS) to find plasma metabolite biomarker candidates that would facilitate the early detection of cisplatin-induced nephrotoxicity...
November 1, 2017: Toxicology Research
Abdel-Gawad S Shalkami, Mohamed I A Hassan, Ahmed A Abd El-Ghany
Cisplatin (CP) is an essential chemotherapeutic drug used over the world against many types of cancer. It has several side effects such as ototoxicity, myelosuppression, and nephrotoxicity. Nephrotoxicity is the most dangerous and is considered a dose-limiting one. Oxidative stress, inflammation, and apoptosis are involved in this toxicity. This study was conducted to focus on the impact of perindopril (PER) against CP-induced nephrotoxicity in rat. Male albino rats were divided to control, rats received a single dose of CP, rats received PER, and rats co-received PER and CP...
July 31, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
Guilherme Augusto Silva Nogueira, Ericka Francislaine Dias Costa, Leisa Lopes-Aguiar, Tathiane Regine Penna Lima, Marília Berlofa Visacri, Eder Carvalho Pincinato, Gustavo Jacob Lourenço, Luciane Calonga, Fernanda Viviane Mariano, Albina Messias de Almeida Milani Altemani, João Maurício Carrasco Altemani, Patrícia Moriel, Carlos Takahiro Chone, Celso Dario Ramos, Carmen Silvia Passos Lima
Head and neck squamous cell carcinoma (HNSCC) is treated with cisplatin (CDDP) and radiotherapy (RT), and distinct results are observed among patients with similar clinicopathological aspects. This prospective study aimed to investigate whether MLH1 c.-93G>A (rs1800734), MSH2 c.211+9C>G (rs2303426), MSH3 c.3133G>A (rs26279), EXO1 c.1765G>A (rs1047840), and EXO1 c.2270C>T (rs9350) single nucleotide polymorphisms (SNPs) of the mismatch repair (MMR) pathway change side effects and response rate of 90 HNSCC patients treated with CDDP and RT...
July 3, 2018: Oncotarget
Murat Dogan, Mustafa Sahin, Nesibe Cetin, Mustafa Yilmaz, Buket Demirci
PURPOSE: To evaluate prestin as a biomarker for the identification of early ototoxicity. MATERIALS AND METHODS: Rats (n = 47) were randomly assigned to five groups: low-dose (LAG) or high-dose (HAG) amikacin (200 and 600 mg/kg/day, respectively, for 10 days), low-dose (LCIS)or high-dose (HCIS) cisplatin (single doses of 5 and 15 mg/kg, respectively, for 3 days), and control (n = 8). At the end of the experiment, measurement of distortion product-evoked otoacoustic emissions (DPOAE) were performed to evaluate hearing, then blood samples and both ear tissues were collected under anesthesia...
July 12, 2018: American Journal of Otolaryngology
Zahra Sarafraz, Aslan Ahmadi, Ahmad Daneshi
OBJECTIVE: Cisplatin is a potent chemotherapeutic agent that is used against a variety of tumors. The most common side effect of cisplatin is ototoxicity. This dose-related hearing impairment is high frequency, bilateral, and permanent. Unfortunately, there is no prophylactic protocol, and, in current clinical practice, the treatment of cancer with cisplatin is interrupted when ototoxicity develops or the resulting hearing impairment is tolerated as an acceptable side effect of cancer treatment...
June 1, 2018: International Tinnitus Journal
Jorrit W van As, Henk van den Berg, Elvira C van Dalen
BACKGROUND: Platinum-based therapy, including cisplatin, carboplatin or oxaliplatin, or a combination of these, is used to treat a variety of paediatric malignancies. Unfortunately, one of the most important adverse effects is the occurrence of hearing loss or ototoxicity. In an effort to prevent this ototoxicity, different platinum infusion durations have been studied. This review is the second update of a previously published Cochrane review. OBJECTIVES: To assess the effects of different durations of platinum infusion to prevent hearing loss or tinnitus, or both, in children with cancer...
July 5, 2018: Cochrane Database of Systematic Reviews
Sofia Waissbluth, Álvaro Del Valle, Angela Chuang, Ana Becker
OBJECTIVES: Platinum-based chemotherapy is effective against a variety of pediatric malignancies. Unfortunately, the use of cisplatin and carboplatin can lead to permanent and progressive sensorineural hearing loss which can affect the quality of life of cancer survivors. The objectives of this study were to evaluate the incidence of platinum-induced ototoxicity in children and analyze potential risk factors. METHODS: Prospective cohort study. All pediatric patients receiving chemotherapy with cisplatin and/or carboplatin from 01/2012 until 10/2017 were included...
August 2018: International Journal of Pediatric Otorhinolaryngology
Eugene H C Wong, You Yi Dong, Mali Coray, Maurizio Cortada, Soledad Levano, Alexander Schmidt, Yves Brand, Daniel Bodmer, Laurent Muller
Exosomes are nanovesicles involved in intercellular communications. They are released by a variety of cell types; however, their presence in the inner ear has not been described in the literature. The aims of this study were to determine if exosomes are present in the inner ear and, if present, characterize the changes in their protein content in response to ototoxic stress. In this laboratory investigation, inner ear explants of 5-day-old Wistar rats were cultured and treated with either cisplatin or gentamicin...
2018: PloS One
Penelope R Brock, Rudolf Maibach, Margaret Childs, Kaukab Rajput, Derek Roebuck, Michael J Sullivan, Véronique Laithier, Milind Ronghe, Patrizia Dall'Igna, Eiso Hiyama, Bénédicte Brichard, Jane Skeen, M Elena Mateos, Michael Capra, Arun A Rangaswami, Marc Ansari, Catherine Rechnitzer, Gareth J Veal, Anna Covezzoli, Laurence Brugières, Giorgio Perilongo, Piotr Czauderna, Bruce Morland, Edward A Neuwelt
BACKGROUND: Cisplatin chemotherapy and surgery are effective treatments for children with standard-risk hepatoblastoma but may cause considerable and irreversible hearing loss. This trial compared cisplatin with cisplatin plus delayed administration of sodium thiosulfate, aiming to reduce the incidence and severity of cisplatin-related ototoxic effects without jeopardizing overall and event-free survival. METHODS: We randomly assigned children older than 1 month and younger than 18 years of age who had standard-risk hepatoblastoma (≤3 involved liver sectors, no metastatic disease, and an alpha-fetoprotein level of >100 ng per milliliter) to receive cisplatin alone (at a dose of 80 mg per square meter of body-surface area, administered over a period of 6 hours) or cisplatin plus sodium thiosulfate (at a dose of 20 g per square meter, administered intravenously over a 15-minute period, 6 hours after the discontinuation of cisplatin) for four preoperative and two postoperative courses...
June 21, 2018: New England Journal of Medicine
Se-Jin Kim, Channy Park, Joon No Lee, Raekil Park
Cisplatin is an alkylating agent that interferes with DNA replication and kills proliferating carcinogenic cells. Several studies have been conducted to attenuate the side effects of cisplatin; one such side effect in cancer patients undergoing cisplatin chemotherapy is ototoxicity. However, owing to a lack of understanding of the precise mechanism underlying cisplatin-induced side effects, management of cisplatin-induced ototoxicity remains unsolved. We investigated the protective effects of fenofibrate, a PPAR-α activator, on cisplatin-induced ototoxicity...
June 13, 2018: Toxicology and Applied Pharmacology
Murat Bakir, Fatime Geyikoglu, Kubra Koc, Salim Cerig
Aims: Cisplatin (CIS) is an influential chemotherapeutic agent in the treatment of several types of malignant solid tumors, but its clinical use is related with ototoxicity. Oleuropein (OLE) is a natural antioxidant and scavenging free radicals. Here, we first explore the efficacy of OLE in pancreas against to the toxicity of CIS and also analyses its mechanism. Materials and Methods: Fifty-six Sprague-Dawley rats were equally divided into eight groups, including, control group which received 7 mg/kg/day CIS intraperitoneally (i...
April 2018: Journal of Cancer Research and Therapeutics
He Li, Yongdong Song, Zuhong He, Xiaoyun Chen, Xianmin Wu, Xiaofei Li, Xiaohui Bai, Wenwen Liu, Boqin Li, Shanshan Wang, Yuechen Han, Lei Xu, Daogong Zhang, Jianfeng Li, Renjie Chai, Haibo Wang, Zhaomin Fan
Hearing loss is the most common sensory disorder in humans, and a significant number of cases is due to the ototoxicity of drugs such as cisplatin that cause hair cell (HC) damage. Thus, there is great interest in finding agents and mechanisms that protect HCs from ototoxic drug damage. It has been proposed that epigenetic modifications are related to inner ear development and play a significant role in HC protection and HC regeneration; however, whether the m6 A modification and the ethyl ester form of meclofenamic acid (MA2), which is a highly selective inhibitor of FTO (fatmass and obesity-associated enzyme, one of the primary human demethylases), can affect the process of HC apoptosis induced by ototoxic drugs remains largely unexplored...
2018: Frontiers in Cellular Neuroscience
Line V Hjelle, Per O M Gundersen, Ragnhild Hellesnes, Mette Sprauten, Marianne Brydøy, Torgrim Tandstad, Tom Wilsgaard, Sophie D Fosså, Jan Oldenburg, Roy M Bremnes, Hege S Haugnes
BACKGROUND: The long-term toxicities after cisplatin-based chemotherapy (CBCT) reveal a remarkable inter-individual variation among testicular cancer survivors (TCSs). Therefore, we assessed long-term platinum (Pt) changes and their associations with CBCT-related late effects in TCSs. MATERIAL AND METHODS: In 77 TCSs treated with CBCT from 1984 to 1990, blood samples for analyses of Pt and a questionnaire including self-reported neuro- and ototoxicity (NTX) symptoms were collected during two follow-up surveys at median 12 (Survey I; SI) and 20 (Survey II; SII) years after treatment...
May 18, 2018: Acta Oncologica
Misa Naganuma, Yumi Motooka, Sayaka Sasaoka, Haruna Hatahira, Shiori Hasegawa, Akiho Fukuda, Satoshi Nakao, Kazuyo Shimada, Koseki Hirade, Takayuki Mori, Tomoaki Yoshimura, Takeshi Kato, Mitsuhiro Nakamura
Objectives: Platinum compounds cause several adverse events, such as nephrotoxicity, gastrointestinal toxicity, myelosuppression, ototoxicity, and neurotoxicity. We evaluated the incidence of renal impairment as adverse events are related to the administration of platinum compounds using the Japanese Adverse Drug Event Report database. Methods: We analyzed adverse events associated with the use of platinum compounds reported from April 2004 to November 2016. The reporting odds ratio at 95% confidence interval was used to detect the signal for each renal impairment incidence...
2018: SAGE Open Medicine
Jong-Hyun Nho, Ho-Kyung Jung, Mu-Jin Lee, Ji-Hun Jang, Mi-Ok Sim, Da-Eun Jeong, Hyun-Woo Cho, Jong-Choon Kim
Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that 10 μM cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells...
April 2018: Toxicological Research
Korhan Kilic, Muhammed Sedat Sakat, Fazile Nur Ekinci Akdemir, Serkan Yildirim, Yavuz Selim Saglam, Seda Askin
INTRODUCTION: Cisplatin is an antineoplastic agent widely used in the treatment of a variety of cancers. Ototoxicity is one of the main side-effects restricting the use of cisplatin. OBJECTIVE: The purpose of this study was to investigate the protective efficacy of gallic acid, in biochemical, functional and histopathological terms, against ototoxicity induced by cisplatin. METHODS: Twenty-eight female Sprague Dawley rats were included. Rats were randomly assigned into four groups of seven animals each...
April 7, 2018: Brazilian Journal of Otorhinolaryngology
Chunkit Fung, Paul Dinh, Shirin Ardeshir-Rouhani-Fard, Kerry Schaffer, Sophie D Fossa, Lois B Travis
Testicular cancer has become the paradigm of adult-onset cancer survivorship, due to the young age at diagnosis and 10-year relative survival of 95%. This clinical review presents the current status of various treatment-related complications experienced by long-term testicular cancer survivors (TCS) free of disease for 5 or more years after primary treatment. Cardiovascular disease and second malignant neoplasms represent the most common potentially life-threatening late effects. Other long-term adverse outcomes include neuro- and ototoxicity, pulmonary complications, nephrotoxicity, hypogonadism, infertility, and avascular necrosis...
2018: Advances in Urology
Xiangrui Guo, Xiaohui Bai, Li Li, Jianfeng Li, Haibo Wang
Cisplatin is widely used in the treatment of various types of cancer. However, it could cause severe side effects such as ototoxicity, which greatly limit the clinical application of cisplatin. Forskolin (FSK) is a diterpene derived from the plant Coleus forskohlii, and has been proven an effective drug for cardiovascular disease, diabetes, and asthma because of its anti-oxidant and anti-inflammatory action. Here, we investigated the effects of FSK in cisplatin-induced ototoxicity, and we found that FSK could significantly protect against cisplatin-induced ototoxicity in both cell line and isolated mouse cochlear...
March 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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