Otoprotective Effects of Zingerone on Cisplatin-Induced Ototoxicity

Lee, Chang Ho; Lee, Da-Hye; Lee, So Min; Kim, And So Young

doi:10.3390/ijms21103503

Cited by 17 publications

(13 citation statements)

References 36 publications

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“…In the same line, Zingerone prevented the development of asthma and alleviated aortic biding‐induced cardiac damage, by activating the Nrf2/antioxidant axis and suppressing inflammatory cytokines production (Zhu et al, 2021). Furthermore, mitigated cisplatin‐induced ototoxicity by suppressing NF‐κB and increasing the heme oxygenase‐1 (HO‐1) (Lee et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Zingerone ameliorates non‐alcoholic fatty liver disease in rats by activating AMPK

Mohammed

2022

Journal of Food Biochemistry

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This study was conducted to test the protective potential of Zingerone against a highfat diet (HFD)-mediated non-alcoholic fatty liver disease (NAFLD) development in rats and examined in this protection is mediated modulating AMP-activated protein kinase (AMPK). Animals were segregated based on their diet and treatment into four groups (n = 6 each): (a) fed standard diet (STD), (b) treated with Zingerone (100 mg/kg), (c) fed HFD, (d) HFD + Zingerone (100 mg/kg), and (e) HFD + Zingerone (100 mg/kg) + compound c (CC) (an AMPK inhibitor) (0.2 mg/kg). The treatment with Zingerone attenuated the gain in final body weights, preserved liver structure, and downregulated the transcription of Bax and cleaved caspase-3. In the HFD and STD-fed rats, Zingerone reduced levels of fasting glucose and insulin and circulatory levels of cholesterol (CHOL) and triglycerides (TGs). Concomitantly, Zingerone enhanced glutathione (GSH) and superoxide dismutase (SOD) levels, depleted levels of malondialdehyde (MDA), and enhanced the nuclear levels of the nuclear factor erythroid 2-related factor 2 (Nrf2).In addition, it lowered the levels of inflammatory cytokines and the nuclear levels of the nuclear factor kappa beta p65 (NF-κB p65). All these biochemical changes were associated with an increment in the phosphorylation of AMPK (p-AMPK) (activation) and reduced mRNA levels of SREBP1 and SREBP2. All observed effects afforded by Zingerone were abolished by CC. In conclusion, Zingerone prevents hepatic oxidative stress, inflammation, and apoptosis by activating AMPK.

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Section: Discussionmentioning

confidence: 99%

Zingerone ameliorates non‐alcoholic fatty liver disease in rats by activating AMPK

Mohammed

2022

Journal of Food Biochemistry

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“…The hearing preservation effects of low-dose RV observed in this study may be mediated by the anti-inflammatory effects of NFκB, IL6 , and IL1β , and anti-oxidative effects of CYP1A1 and cytosolic RAGE. CXP increases oxidative stress and the pro-inflammatory cytokines NFκB and IL6 [ 23 ]. RV has been reported to decrease RAGE and NFκB activities, thereby restoring oxidative stress and inflammation-related diseases [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…The ABR thresholds at 4, 8, 16, and 32 kHz were measured using the SmartEP system as described previously [ 23 , 24 ]. The rats were intraperitoneally administered zoletil (40 mg/kg) and xylazine (10 mg/kg) prior to the ABR measurements.…”

Section: Methodsmentioning

confidence: 99%

Dose-Dependent Effects of Resveratrol on Cisplatin-Induced Hearing Loss

Lee

Kim

Lee

et al. 2020

IJMS

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Previous preclinical studies have demonstrated the otoprotective effects of resveratrol (RV) at low doses. This study aimed to investigate the dose-dependent effects of RV in rats with cisplatin (CXP)-induced hearing loss. Sprague-Dawley rats (8-weeks old) were divided into six treatment groups (n = 12/group) and treated as follows: control, 0.5 mg/kg RV, 50 mg/kg RV, CXP, 0.5 mg/kg RV + CXP), and 50 mg/kg RV + CXP groups. CXP (3 mg/kg) was intraperitoneally injected for 5 days. RV (0.5 or 50 mg/kg) was intraperitoneally injected for 10 days from the first day of CXP administration. Auditory brainstem response (ABR) thresholds were measured before and within 3 days at the end of the drug administration. Cochlear tissues were harvested, and the outer hair cells were examined using cochlear whole mounts. The mRNA expression of NFκB, IL6, IL1β, and CYP1A1, and protein levels of aryl hydrocarbon receptor (AhR) and cytosolic and nuclear receptor for advanced glycation endproducts (RAGE) were evaluated. The ABR threshold increased in the 50 mg/kg RV and CXP groups at 4, 8, 16, and 32 kHz. The 0.5 mg/kg RV + CXP group demonstrated decreased hearing thresholds at 4 and 32 kHz compared to the CXP group. Cochlear whole-mount analysis revealed loss of outer hair cells in the 50 mg/kg RV and CXP groups and partial prevention of these cells in the 0.5 mg/kg RV + CXP group. The mRNA expressions of NFκB, IL6, and IL1β were increased in the 50 mg/kg RV and CXP groups compared to the control group. In contrast, these levels were decreased in the 0.5 mg/kg RV + CXP group compared to the CXP group. The mRNA expression of CYP1A1 was increased in the CXP group, while it was decreased in the 0.5 mg/kg RV + CXP group compared to the control group. The protein levels of AhR and cytosolic RAGE decreased in the 0.5 mg/kg RV group. Low-dose RV had partial otoprotective effects on CXP ototoxicity. The otoprotective effects of RV may be mediated through anti-oxidative (CYP1A1 and RAGE) and anti-inflammatory (NFκB, IL6, and IL1β) responses. High-dose RV exerted an inflammatory response and did not ameliorate CXP-induced ototoxicity.

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“…A platinum-iridium needle electrode was used as recording electrode. The ABR test used 4, 8, 12, 16, 20 and 32 kHz in the Blackman envelope with tone burst stimuli with fluctuation time 1000 ms [19, 20]. The lowest intensity level obtained with the III wave was accepted as the hearing threshold of the nude mouse at that frequency.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the Effect of Mesenchymal Stem Cells on Chemotherapy Response for Neuroblastoma Treatment in an Experimental Animal Model

Aktaş

Olgun

Eskicioğlu

et al. 2020

Preprint

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High-dose cisplatin (CDDP) causes dose-limiting side effects in neuroblastoma (NB) treatment. Mesenchymal stem cells (MSC) are a current research area in cellular treatments due to multipotential characteristics. The aim of this study is to assess the interaction of MSC with CDDP in an athymic nude mouse NB model. Athymic male nude mice (n=28) were injected subcutaneously with C1300 NB cell line. After tumor growth to 1 cm diameter in 7-10 days, mice were randomly assigned to one of 4 experimental groups of control, CDDP treatment, MSC treatment and CDDP+MSC treatment with 7 mice in each group. Animals had basal auditory tests performed and had physiological serum or CDDP (20 mg/kg) injected into the peritoneum and were intravenously injected with 1×105 MSC once. Seven days later, hearing tests were performed again and the animals were sacrificed. Tumor tissue was assessed in terms of necrosis, apoptosis and viability. Apoptosis was evaluated with annexin V+PI flow cytometry analysis and TUNEL. Additionally, the MSC rate within the tumor was assessed with flow cytometry for triple CD34+ CD44+ and CD117-expression. Additionally, liver, kidney, brain and cochlear tissue were analyzed with light microscopy in terms of systemic side effect profile. Expression of the cochlear cell proteins of calretinin, math-1 and myosin2A were immunohistochemically assessed in ear sections. Statistical analysis used the nonparametric Kruskal Wallis and Mann Whitney U tests with p<0.05 significance. Tumor tissues were found to have statistically significantly higher levels of necrosis in the CDDP group and CDDP+MSC group compared to the control and MSC groups (p=0.001, p=0.006). The CDDP+MSC group had lower tumor necrosis rates than the CDDP group but this was not observed to have statistical significance (p=0.05). MSC did not change the tumor dimensions in the CDDP group (p=0.557). The groups administered MSC had higher triple CD34+ CD44+ and CD117- expression within tumor tissue compared to the control and CDDP groups. In the inner ear, the expression of cochlear cell proteins calretinin, math-1 and myosin2A were identified to be highest in the groups administered MSC. Auditory tests observed that the 15-decibel loss at 12, 16, 20 and 32 kHz frequencies in both ears with CDDP was resolved with MSC administration. With this study, IV administration of MSC treatment was observed to prevent the hearing loss caused by CDDP without disrupting the antitumor effect of CDDP. Systemic MSC may be assessed for clinical use to reduce the side effects of CDDP.

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Otoprotective Effects of Zingerone on Cisplatin-Induced Ototoxicity

Cited by 17 publications

References 36 publications

Zingerone ameliorates non‐alcoholic fatty liver disease in rats by activating AMPK

Zingerone ameliorates non‐alcoholic fatty liver disease in rats by activating AMPK

Dose-Dependent Effects of Resveratrol on Cisplatin-Induced Hearing Loss

Evaluation of the Effect of Mesenchymal Stem Cells on Chemotherapy Response for Neuroblastoma Treatment in an Experimental Animal Model

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