Targeting dysregulation of redox homeostasis in noise-induced hearing loss: Oxidative stress and ROS signaling

Fetoni, Anna Rita; Paciello, Fabiola; Rolesi, Rolando; Paludetti, Gaetano; Troiani, Diana

doi:10.1016/j.freeradbiomed.2019.02.022

Cited by 137 publications

(131 citation statements)

References 239 publications

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“…The major results indicated that polyphenols administrated in conjunction with cisplatin can exert both anti-oxidant and pro-oxidant effects; however, the polyphenolic compounds show different mechanisms of action depending on cell context and dosage. In fact, cisplatin in the cochlea causes an excessive ROS production resulting in redox imbalance and cell death similarly to what occurs in noise-induced hearing loss and presbycusis 21,[34][35][36][37] . Here, we demonstrated that the increase of Nrf-2 nuclear translocation and HO-1 fluorescence in hair cells and spiral ganglion neurons (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…FA concentrations were extrapolated from previous in vivo studies in the guinea pig 29 . Curcumin or FA solution were injected 1 hour before cisplatin administration and once daily for the following 3 days, considering that previous studies demonstrated that this therapeutic window is effective in preventing cochlear exogenous insults [20][21][22] .…”

Section: Methodsmentioning

confidence: 99%

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The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity

Paciello

Fetoni

Mezzogori

et al. 2020

Sci Rep

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Platinum-based agents, such as cisplatin, form the mainstay of currently used chemotherapeutic regimens for several malignancies; however, the main limitations are chemoresistance and ototoxic side effects. In this study we used two different polyphenols, curcumin and ferulic acid as adjuvant chemotherapeutics evaluating (1) in vivo their antioxidant effects in protecting against cisplatin ototoxicity and (2) in vitro the transcription factors involved in tumor progression and cisplatin resistance. We reported that both polyphenols show antioxidant and oto-protective activity in the cochlea by up-regulating Nrf-2/HO-1 pathway and downregulating p53 phosphorylation. However, only curcumin is able to influence inflammatory pathways counteracting NF-κB activation. In human cancer cells, curcumin converts the anti-oxidant effect into a pro-oxidant and anti-inflammatory one. Curcumin exerts permissive and chemosensitive properties by targeting the cisplatin chemoresistant factors Nrf-2, NF-κB and STAT-3 phosphorylation. Ferulic acid shows a biphasic response: it is pro-oxidant at lower concentrations and anti-oxidant at higher concentrations promoting chemoresistance. Thus, polyphenols, mainly curcumin, targeting ROS-modulated pathways may be a promising tool for cancer therapy. Thanks to their biphasic activity of antioxidant in normal cells undergoing stressful conditions and pro-oxidant in cancer cells, these polyphenols probably engage an interplay among the key factors Nrf-2, NF-κB, STAT-3 and p53. Cisplatin chemotherapy has been a mainstay of cancer treatment 1. In general, cisplatin is considered a cytotoxic drug which kills cancer cells by the formation of intra-and inter-strand DNA crosslinks as well as cisplatin DNA adducts 2-4. The molecular mechanisms of action are complex and involve multiple events that include induction of oxidative stress as characterized by reactive oxygen species (ROS) production and lipid peroxidation, inflammation by activating pro-inflammatory factors, induction of p53-dependent signaling pathways 5. However, cisplatin chemotherapy is also associated with substantial side effects that include ototoxic damage 6-9. Elevation of hearing threshold, mainly for the higher frequencies, has been reported in 22 to 75% of adult patients 10 and 26 to 90% of pediatric patients 11 ; it results in significant and permanent hearing loss that is especially debilitating in young children 11. A growing body of research is dedicated to elucidate the molecular mechanisms implicated in cisplatin toxicity and resistance, including oxidative stress and inflammation 4,12-15. Still, the molecular mechanisms underlying the enhanced sensitivity or resistance to cisplatin-induced apoptosis and cisplatin adverse effects are poorly understood. In the present research we considered that combination therapies of cisplatin with other drugs have become challenging in the treatment of human cancers to overcome drug resistance and reduce the undesirable side effects. Currently, natural products or nutraceuticals are...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity

Paciello

Fetoni

Mezzogori

et al. 2020

Sci Rep

Self Cite

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“…Therefore, we speculate that the chemical composition might play an important role in PM 2.5 induced by an increased production of ROS in HK-2 cell. Overproduction of ROS may lead to severe damage to DNA and proteins and cause an imbalance in cell homeostasis, resulting in autophagy, apoptosis and cell death [44]. Cells also need to increase the expression of antioxidant genes to maintain intracellular homeostasis against oxidative stress [4].…”

Section: Discussionmentioning

confidence: 99%

The activation of antioxidant and apoptosis pathways involved in damage of human proximal tubule epithelial cells by PM2.5 exposure

et al. 2020

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Background: Exposure to airborne fine particulate matter (PM 2.5 ) has been reported to be harmful to the human kidney. However, whether the activation of oxidative stress and cell apoptosis plays key roles in the nephrotoxicity caused by PM 2.5 exposure is still poorly understood. The aim of this study was to explore the mechanism of cytotoxicity after PM 2.5 exposure in human proximal tubule epithelial cells (HK-2 cells).Results: PM 2.5 exposure resulted in a significant decrease in cell viability, with an increase in LDH release and the early kidney damage marker kidney injury molecule-1 (KIM-1) expression in a dose-dependent manner and timedependent manner. PM 2.5 exposure induced reactive oxygen species (ROS) generation and markedly elevated apoptosis in HK-2 cells. In addition, PM 2.5 exposure resulted in the activation of antioxidant pathway, as evidenced by the increased expressions of Nrf2, HO-1 and NQO1 and decreased expression of Keap1. Moreover, PM 2.5 exposure also induced the activation of apoptotic pathway, as evidenced by the increased expressions of pro-apoptotic proteins Bax, caspase-3 and caspase-8 and decreased expression of antiapoptotic protein Bcl-2. Conclusions:Our results demonstrated that both antioxidant pathway and apoptotic pathway played critical roles in the damage mediated by PM 2.5 in HK-2 cells. This study would give us a strategy to prevent the impairment of renal function by PM 2.5 induced through repression of oxidative stress and apoptosis.

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“…In the present study, both CO and NO 2 levels are relatively higher in highly urbanized region and boomtown than in other areas (Table 3). Notably, both noise and air pollution may damage the cochlear HCs via oxidative stress [60], hypoxia-induced reactive oxygen species, and HC damage [48]. Although we found a statistically significant association between air pollution and subsequent SHL, the present study had the following limitations that need to be considered: (1) The noise levels in the studied area and the genetic variants in the studied subjects, which are considered as important risk factors for SHL, were not clarified in the present study, and without the noise-level data, the scope and significance of the study are limited.…”

Section: Discussionmentioning

confidence: 99%

Increased Risk of Sensorineural Hearing Loss as a Result of Exposure to Air Pollution

Chang

Tsai

Lee

et al. 2020

IJERPH

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Whether exposure to air pollution is associated with developing sensorineural hearing loss (SHL) remains controversial. Using data from the National Health Insurance Research Database, we recruited a total of 75,767 subjects aged older than 20 years with no history of SHL from 1998 to 2010, and they were followed up until SHL was observed, they withdrew from the National Health Insurance program, or the study ended. The subjects were evenly exposed to low-level, mid-level, and high-level carbon monoxide (CO) and nitrogen dioxide (NO2). The incidence rate ratio of SHL for patients exposed to high-level CO was 1.24 (95% confidence interval (CI) = 1.14–1.36). The NO2 pollutants increased the incidence rate ratios of SHL in mid-level NO2 and high-level NO2 exposures by 1.10 (95% CI = 1.10–1.32) and 1.36 (95% CI = 1.24–1.49) times, respectively. The adjusted hazard ratio (adj. HR) of SHL in patients exposed to high-level CO was 1.45 (95% CI = 1.31–1.59), relative to that of patients exposed to low-level CO. Compared to patients exposed to low-level NO2, patients exposed to mid-level NO2 (adj. HR = 1.40, 95% CI = 1.27–1.54) and high-level NO2 (adj. HR = 1.63, 95% CI = 1.48–1.81) had a higher risk of developing SHL. The increased risk of SHL following the increased concentrations of air pollutants (CO and NO2) was statistically significant in this study. In conclusion, the subjects’ exposure to air pollution exhibited a significantly higher risk of developing SHL in Taiwan.

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Targeting dysregulation of redox homeostasis in noise-induced hearing loss: Oxidative stress and ROS signaling

Cited by 137 publications

References 239 publications

The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity

The dual role of curcumin and ferulic acid in counteracting chemoresistance and cisplatin-induced ototoxicity

The activation of antioxidant and apoptosis pathways involved in damage of human proximal tubule epithelial cells by PM2.5 exposure

Increased Risk of Sensorineural Hearing Loss as a Result of Exposure to Air Pollution

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