Melatonin Alleviates the Oxygen–Glucose Deprivation/Reperfusion-Induced Pyroptosis of HEI-OC1 Cells and Cochlear Hair Cells via MT-1,2/Nrf2 (NFE2L2)/ROS/NLRP3 Pathway

Zheng, Yu; Gao, Na; Zhang, Weixun; Ma, Rui; Chi, Fang‐Lu; Gao, Zhen; Cong, Ning

doi:10.1007/s12035-022-03077-x

Cited by 6 publications

(6 citation statements)

References 35 publications

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“…In this regard, our previous report showed that melatonin promotes the transcriptional activity of Nrf2 and subsequently increases the expression of glutathione‐synthesizing enzymes by activating melatonin receptors, thereby maintaining glutathione homeostasis in the hippocampus of klotho mutant mice, an aging model 8 . Recent studies also showed that melatonin activates Nrf2 signaling by activating melatonin receptors, which in turn upregulates the enzymatic antioxidant system and attenuates oxidative stress 73,96 . Consistently, the present study revealed that repeated post‐KA treatment with ramelteon increased the nuclear translocation and DNA binding activity of Nrf2 in the mouse hippocampus following KA‐induced seizures, thereby restoring glutathione homeostasis and inhibiting oxidative stress.…”

Section: Discussionsupporting

confidence: 88%

“…8 Recent studies also showed that melatonin activates Nrf2 signaling by activating melatonin receptors, which in turn upregulates the enzymatic antioxidant system and attenuates oxidative stress. 73,96 Consistently, the present study revealed that repeated post-KA treatment with ramelteon increased the nuclear translocation and DNA binding activity of Nrf2 in the mouse hippocampus following KA-induced seizures, thereby restoring glutathione homeostasis and inhibiting oxidative stress. Similarly, Wang et al 41 reported that ramelteon increases brain and serum glutathione levels by activating Nrf2 signaling after traumatic brain injury in mice.…”

Section: Discussionsupporting

confidence: 83%

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Ramelteon attenuates hippocampal neuronal loss and memory impairment following kainate‐induced seizures

Park,

Hwang,

Nguyen

et al. 2023

Journal of Pineal Research

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Evidence suggests that the neuroprotective effects of melatonin involve both receptor‐dependent and ‐independent actions. However, little is known about the effects of melatonin receptor activation on the kainate (KA) neurotoxicity. This study examined the effects of repeated post‐KA treatment with ramelteon, a selective agonist of melatonin receptors, on neuronal loss, cognitive impairment, and depression‐like behaviors following KA‐induced seizures. The expression of melatonin receptors decreased in neurons, whereas it was induced in astrocytes 3 and 7 days after seizures elicited by KA (0.12 μg/μL) in the hippocampus of mice. Ramelteon (3 or 10 mg/kg, i.p.) and melatonin (10 mg/kg, i.p.) mitigated KA‐induced oxidative stress and impairment of glutathione homeostasis and promoted the nuclear translocation and DNA binding activity of Nrf2 in the hippocampus after KA treatment. Ramelteon and melatonin also attenuated microglial activation but did not significantly affect astroglial activation induced by KA, despite the astroglial induction of melatonin receptors after KA treatment. However, ramelteon attenuated KA‐induced proinflammatory phenotypic changes in astrocytes. Considering the reciprocal regulation of astroglial and microglial activation, these results suggest ramelteon inhibits microglial activation by regulating astrocyte phenotypic changes. These effects were accompanied by the attenuation of the nuclear translocation and DNA binding activity of nuclear factor κB (NFκB) induced by KA. Consequently, ramelteon attenuated the KA‐induced hippocampal neuronal loss, memory impairment, and depression‐like behaviors; the effects were comparable to those of melatonin. These results suggest that ramelteon‐mediated activation of melatonin receptors provides neuroprotection against KA‐induced neurotoxicity in the mouse hippocampus by activating Nrf2 signaling to attenuate oxidative stress and restore glutathione homeostasis and by inhibiting NFκB signaling to attenuate neuroinflammatory changes.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 83%

Ramelteon attenuates hippocampal neuronal loss and memory impairment following kainate‐induced seizures

Park,

Hwang,

Nguyen

et al. 2023

Journal of Pineal Research

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“…A recent study shows that melatonin alleviates pyroptosis of hair cells via the MT-1 and MT-2/Nrf2 (NFE2L2)/ROS/NLRP3 pathway, which further supports the conjecture that melatonin can be used for the treatment of ISSNHL ( 70 ). In addition, melatonin also has an antidepressant function ( 71 ) and improves tinnitus ( 72 ).…”

Section: Discussionsupporting

confidence: 52%

Reassessment of oxidative stress in idiopathic sudden hearing loss and preliminary exploration of the effect of physiological concentration of melatonin on prognosis

Song,

Ouyang,

Xiong

et al. 2023

Front. Neurol.

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Background and purposeThe pathogenesis of idiopathic sudden sensorineural hearing loss (ISSNHL) is still unclear, and there is no targeted treatment. This research aimed to verify the role of oxidative stress in ISSNHL and explore whether melatonin has a protective effect on hearing.Materials and methodsA total of 43 patients with ISSNHL and 15 healthy controls were recruited to detect the level of melatonin, reactive oxygen species (ROS), and total antioxidant capacity (TAC) in the blood and compared before and after treatment. Multivariate logistic regression models were performed to assess the factors relevant to the occurrence and improvement of ISSNHL.ResultsThe patients with ISSNHL showed significantly higher ROS levels than controls (4.42 ± 4.40 vs. 2.30 ± 0.59; p = 0.031). The levels of basal melatonin were higher (1400.83 ± 784.89 vs. 1095.97 ± 689.08; p = 0.046) and ROS levels were lower (3.05 ± 1.81 vs. 5.62 ± 5.56; p = 0.042) in the effective group as compared with the ineffective group. Logistic regression analysis showed that melatonin (OR = 0.999, 95% CI 0.997–1.000, p = 0.049), ROS (OR = 1.154, 95% CI 1.025–2.236, p = 0.037), and vertigo (OR = 3.011, 95% CI 1.339–26.983, p = 0.019) were independent factors associated with hearing improvement. Besides, the level of melatonin (OR = 0.999, 95% CI 0.998–1.000, p = 0.023) and ROS (OR = 3.248, 95% CI 1.109–9.516, p = 0.032) were associated with the occurrence of ISSNHL.ConclusionOur findings may suggest oxidative stress involvement in ISSNHL etiopathogenesis. The level of melatonin and ROS, and vertigo appear to be predictive of the effectiveness of hearing improvement following ISSNHL treatment.

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“…ROS also stimulate the expression of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) in the ROS/NLRP3 pathway as negative feedback. Melatonin can inhibit the ROS/NLRP3 pathway by stimulating the expression of Nrf2 and HO-1 through melatonin receptors 1A and 1B to reduce ROS-induced pyroptosis of cochlear hair cells [ 68 ]. Altered expressions of multiple pro-pyroptotic molecules have been detected in presbycusis; however, this molecular regulatory network is not clearly understood, and further research is needed.…”

Section: Pyroptosis and Degenerative Diseases Of The Elderlymentioning

confidence: 99%

Pyroptosis and degenerative diseases of the elderly

et al. 2023

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Pyroptosis is a recently described mechanism of programmed cell death mediated by proteins of the gasdermin family. Widely recognized signaling cascades include the classical, non-classical, caspase-3-dependent gasdermin E and caspase-8-dependent gasdermin D pathways. Additional pyroptotic pathways have been subsequently reported. With the rising prevalence of advanced age, the role of pyroptosis in the degenerative diseases of the elderly has attracted increased research attention. This article reviews the primary mechanisms of pyroptosis and summarizes progress in the research of degenerative diseases of the elderly such as presbycusis, age-related macular degeneration, Alzheimer’s disease, intervertebral disc degeneration, and osteoarthritis.

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Melatonin Alleviates the Oxygen–Glucose Deprivation/Reperfusion-Induced Pyroptosis of HEI-OC1 Cells and Cochlear Hair Cells via MT-1,2/Nrf2 (NFE2L2)/ROS/NLRP3 Pathway

Cited by 6 publications

References 35 publications

Ramelteon attenuates hippocampal neuronal loss and memory impairment following kainate‐induced seizures

Ramelteon attenuates hippocampal neuronal loss and memory impairment following kainate‐induced seizures

Reassessment of oxidative stress in idiopathic sudden hearing loss and preliminary exploration of the effect of physiological concentration of melatonin on prognosis

Pyroptosis and degenerative diseases of the elderly

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