Cisplatin ototoxicity

PURPOSE: This study aims to characterize patterns in ototoxicity monitoring and identify potential barriers to audiologic follow-up. METHODS: We performed a single-institution retrospective cohort study on adult (≥ 18 years old) cancer patients treated with cisplatin from January 2014 to September 2021. Our primary outcomes were rates of baseline and post-treatment audiograms at the following time points: 3, 6, 12, and greater than 12 months...

Cisplatin is widely employed in clinical oncology as an anticancer chemotherapy drug in clinical practice and is known for its severe ototoxic side effects. Prior research indicates that the accumulation of reactive oxygen species (ROS) plays a pivotal role in cisplatin's inner ear toxicity. Hesperidin is a flavanone glycoside extracted from citrus fruits that has anti-inflammatory and antioxidant effects. Nonetheless, the specific pharmacological actions of hesperidin in alleviating cisplatin-induced ototoxicity remain elusive...

PURPOSE: Cisplatin is a low-cost clinical anti-tumor drug widely used to treat solid tumors. However, its use could damage cochlear hair cells, leading to irreversible hearing loss. Currently, there appears one drug approved in clinic only used for reducing ototoxicity associated with cisplatin in pediatric patients, which needs to further explore other candidate drugs. METHODS: Here, by screening 1967 FDA-approved drugs to protect cochlear hair cell line (HEI-OC1) from cisplatin damage, we found that Tedizolid Phosphate (Ted), a drug indicated for the treatment of acute infections, had the best protective effect...

Cisplatin use is often limited by its ototoxic side effects, which can lead to irreversible hearing loss. Preventing cisplatin-induced ototoxicity is crucial to improve patient outcomes. Fluoxetine and fluvoxamine, both SSRI antidepressants, inhibit the NLRP3 inflammasome, a potential therapeutic target for preventing ototoxicity. However, human studies have not evaluated if these antidepressants may protect against cisplatin-induced ototoxicity. The object of this study is to assess the association between fluoxetine or fluvoxamine use and the incidence of hearing loss or tinnitus in a large cohort of patients receiving cisplatin chemotherapy...

Nobiletin, a citrus polymethoxy flavonoid with antiapoptotic and antioxidative properties, could safeguard against cisplatin-induced nephrotoxicity and neurotoxicity. Cisplatin, as the pioneer of anti-cancer drug, the severe ototoxicity limits its clinical applications, while the effect of nobiletin on cisplatin-induced ototoxicity has not been identified. The current study investigated the alleviating effect of nobiletin on cisplatin-induced ototoxicity and the underlying mechanisms. Apoptosis and ROS formation were evaluated using the CCK-8 assay, Western blotting, and immunofluorescence, indicating that nobiletin attenuated cisplatin-induced apoptosis and oxidative stress...

Ototoxicity is a devastating direct, irreversible side effect of platinum use in children with cancer, with its consequent effect on speech, language and social development, quality of life and adult productivity. Cisplatin, an essential chemotherapeutic agent for the treatment of solid tumors in children, is a DNA cross-linking agent. Which causes hearing loss in 50-70% of cisplatin treated children. Fortunately, to prevent hearing loss, sodium thiosulfate (STS), which binds to cisplatin, and reduces the superoxides in both tumor and outer hair cells of the cochlea has now been discovered to be an effective and safe otoprotectant if administered correctly...

Cisplatin, a chemotherapeutic agent, can cause nephrotoxic and ototoxic injuries. Using a mouse model of repeated low dose cisplatin (RLDC), we compared the kidneys of cisplatin- and vehicle-treated mice on days 3 (early injury phase) and 35 (late injury/recovery phase) after the final treatment. RNA-seq analyses revealed increases in the expression of markers of kidney injury (e.g., lipocalin 2 and kidney injury molecule 1) and fibrosis (e.g., collagen 1, fibronectin, and vimentin 1) in RLDC mice. In addition, we observed increased expression of polyamine catabolic enzymes (spermidine/spermine N1 -acetyltransferase, Sat1 , and spermine oxidase, Smox ) and decreased expression of ornithine decarboxylase ( Odc1 ), a rate-limiting enzyme in polyamine synthesis in mice subjected to RLDC...

OBJECTIVE: The genotype-phenotype relationship in cisplatin-induced ototoxicity remains unclear. By assessing early shifts in distortion product otoacoustic emission (DPOAE) levels after initial cisplatin administration, we aimed to discriminate patients' susceptibility to cisplatin-induced ototoxicity and elucidate their genetic background. STUDY DESIGN: A prospective cross-sectional study. SETTING: Tertiary referral hospital in Japan. PATIENTS: Twenty-six patients with head and neck cancer were undergoing chemoradiotherapy with three cycles of 100 mg/m2 cisplatin...

BACKGROUND: Childhood cancer survivors (CCS) exposed to platinum chemotherapy are at an increased risk of developing hearing loss and reporting decreased quality of life (QOL). This study compared two QOL measures; one developed for children with hearing loss, The Hearing Environments and Refection on Quality of Life (HEAR-QL), and one validated in CCS, the Patient-Reported Outcomes Measurement Information System (PROMIS), to assess their ability to evaluate QOL deficits in this population...

Ferroptosis, characterized by iron-dependent lipid reactive oxygen species (ROS) accumulation, plays a pivotal role in cisplatin-induced ototoxicity. Existing research has suggested that in cisplatin-mediated damage to auditory cells and hearing loss, ferroptosis is partially implicated. 4-Octyl itaconate (4-OI), derived from itaconic acid, effectively permeates cell membranes, showcasing potent anti-inflammatory as well as antioxidant effects in several disease models. Our study aimed to investigate the effect of 4-OI on cisplatin-induced ferroptosis and the underlying molecular mechanisms...

Cisplatin is an effective chemotherapeutic drug for different cancers, but it also causes severe and permanent hearing loss. Oxidative stress and mitochondrial dysfunction in cochlear hair cells (HCs) have been shown to be important in the pathogenesis of cisplatin-induced hearing loss (CIHL). CDGSH iron sulfur domain 1 (CISD1, also known as mitoNEET) plays a critical role in mitochondrial oxidative capacity and cellular bioenergetics. Targeting CISD1 may improve mitochondrial function in various diseases. However, the role of CISD1 in cisplatin-induced ototoxicity is unclear...

Cisplatin (CDDP) is broadly employed to treat different cancers, whereas there are no drugs approved by the Food and Drug Administration (FDA) for preventing its side effects, including ototoxicity. Quercetin (QU) is a widely available natural flavonoid compound with anti-tumor and antioxidant properties. The research was designed to explore the protective effects of QU on CDDP-induced ototoxicity and its underlying mechanisms in male C57BL/6 J mice and primary cultured pericytes (PCs). Hearing changes, morphological changes of stria vascularis, blood labyrinth barrier (BLB) permeability and expression of apoptotic proteins were observed in vivo by using the auditory brainstem response (ABR) test, HE staining, Evans blue staining, immunohistochemistry, western blotting, etc...

Cisplatin (CDDP) stands out as an effective chemotherapeutic agent; however, its application is linked to the development of significant adverse effects, notably nephro- and ototoxicity. The human organic cation transporter 2 (hOCT2), found in abundance in the basolateral membrane domain of renal proximal tubules and the Corti organ, plays a crucial role in the initiation of nephro- and ototoxicity associated with CDDP by facilitating its uptake in kidney and ear cells. Given its limited presence in cancer cells, hOCT2 emerges as a potential druggable target for mitigating unwanted toxicities associated with CDDP...

A 51-year-old man with a history of cisplatin treatment for a right testicular tumor underwent microvascular decompression for hemifacial spasm. At an early stage in the surgical procedure, the intraoperative auditory brainstem response (ABR) was diminished despite a relatively minimally invasive approach, resulting in irreversible hearing loss. Cisplatin is known to cause dose-dependent hearing impairment primarily affecting the cochlea, but it can also induce neurotoxicity. In the present case, prior cisplatin administration may have caused fragility of the cochlear nerve as well...

Cisplatin is a highly effective chemotherapeutic agent, but it can cause sensorineural hearing loss (SNHL) in patients. Cisplatin-induced ototoxicity is closely related to the accumulation of reactive oxygen species (ROS) and subsequent death of hair cells (HCs) and spiral ganglion neurons (SGNs). Despite various strategies to combat ototoxicity, only one therapeutic agent has thus far been clinically approved. Therefore, we have developed a gene therapy concept to protect cochlear cells from cisplatin-induced toxicity...

Cisplatin-induced hearing loss is a common side effect of cancer chemotherapy in clinics, however, the mechanism of cisplatin-induced ototoxicity is still not completely clarified. Cisplatin-induced ototoxicity is mainly associated with the production of reactive oxygen species, activation of apoptosis, and accumulation of intracellular lipid peroxidation, which also is involved in ferroptosis induction. In this study, the expression of TfR1, a ferroptosis biomarker, was upregulated in the outer hair cells of cisplatin-treated mice...

Cisplatin is a commonly used chemotherapy that causes permanent hearing loss by injuring cochlear hair cells. The underlying mechanisms that drive hair cell loss remain unknown, but mitochondria have emerged as potential mediators of cisplatin ototoxicity. Direct observation of changes in hair cell mitochondrial function are challenging because the mammalian inner ear is optically inaccessible. Here, we perform live in vivo imaging of hair cells within the zebrafish lateral-line organ to evaluate the role of mitochondria in cisplatin ototoxicity...

Cisplatin (CisPt)-induced ototoxicity (CIO) is delineated as a consequence of CisPt-induced intracellular generation of reactive oxygens species (ROS) which can be circumvented by Bucillamine (BUC; an antioxidant drug with sulfhydryl groups) and Diltiazem (DLT, L-type calcium channel blocker). However, its effective accumulation in the Organ of Corti and cell cytoplasm is desired. Therefore, a biocompatible BUC and DLT nanoparticles (NPs)-impregnated dual stimuli-responsive formulation (NanoSensoGel) has been presented here with ROS and thermo-responsive properties for the sustained and efficient delivery of drugs...

OBJECTIVE: Intratympanic injections are a safe, well tolerated procedure routinely performed by ENT's specialists. Intratympanic injections of gels have the potential to deliver therapeutics into the cochlea through the round window membrane prolonging the release of drugs in the inner ear compartment. Aim of the present review is to summarize clinical trials testing pharmacological treatments for inner ear pathologies through intratympanic gel formulations. DATA SOURCES: Online databases (Google scholar and PubMed) and registers (Clinicaltrials...

Carboplatin (cis-diamine (1,1-cyclobutandicarboxylaso)‑platinum (II)) is a second-generation antineoplastic drug, which is widely used for chemotherapy of lung, colon, breast, cervix, testicular and digestive system cancers. Although preferred over cisplatin due to the lower incidence of nephrotoxicity and ototoxicity, efficient carboplatin delivery remains as a major challenge. In this study, carboplatin loaded alginate- poly(amidoamine) (PAMAM) hybrid nanoparticles (CAPs) with mean sizes of 192.13 ± 4...