Metformin attenuates cadmium-induced degeneration of spiral ganglion neuron via restoring autophagic flux in primary culture

Li, Qian; Wang, Liuqian; Ji, Di; Yu, Wei; Zhang, Yan; Xiang, Yanghong; Zhou, Chao; Wang, Liting; Deng, Ping; Pi, Huifeng; Lu, Yonghui; Ma, Qibin; He, Mindi; Zhang, Lei; Yu, Zhengping; Deng, Anchun

doi:10.1016/j.jinorgbio.2022.111901

Cited by 6 publications

(6 citation statements)

References 46 publications

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“…This is evident in both ototoxic drugs and degenerative tinnitus. In fact, autophagy protects against ototoxic exposure to cadmium [71]. Similarly, cisplatin-induced HC loss is prevented by the autophagy inducer trehalose [72] in a way that is suppressed by pre-administering the autophagy inhibitor 3-methyl adenine (3-MA).…”

Section: The Role Of Autophagy In Maintaining the Structure Of Ohc Sc...mentioning

confidence: 99%

“…In detail, when the autophagy-stimulating protein ATG5 is suppressed, OHC develops neuronal inclusions staining for p62 and ubiquitin along with abnormal organelles, including mitochondria, which indicates how basal autophagy is essential for HCs [61]. This is disrupted in all conditions leading to tinnitus, including the effects of ototoxic AGs [71,104]. The essential role of autophagy in the inner ear extends to the vestibular system, where the autophagy initiator Atg4b is needed for the development of otoconia [105].…”

Section: Potential Benefits Of Nutraceuticalsmentioning

confidence: 99%

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The Relevance of Autophagy within Inner Ear in Baseline Conditions and Tinnitus-Related Syndromes

Lazzeri,

Biagioni,

Ferrucci

et al. 2023

IJMS

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Tinnitus is the perception of noise in the absence of acoustic stimulation (phantom noise). In most patients suffering from chronic peripheral tinnitus, an alteration of outer hair cells (OHC) starting from the stereocilia (SC) occurs. This is common following ototoxic drugs, sound-induced ototoxicity, and acoustic degeneration. In all these conditions, altered coupling between the tectorial membrane (TM) and OHC SC is described. The present review analyzes the complex interactions involving OHC and TM. These need to be clarified to understand which mechanisms may underlie the onset of tinnitus and why the neuropathology of chronic degenerative tinnitus is similar, independent of early triggers. In fact, the fine neuropathology of tinnitus features altered mechanisms of mechanic-electrical transduction (MET) at the level of OHC SC. The appropriate coupling between OHC SC and TM strongly depends on autophagy. The involvement of autophagy may encompass degenerative and genetic tinnitus, as well as ototoxic drugs and acoustic trauma. Defective autophagy explains mitochondrial alterations and altered protein handling within OHC and TM. This is relevant for developing novel treatments that stimulate autophagy without carrying the burden of severe side effects. Specific phytochemicals, such as curcumin and berberin, acting as autophagy activators, may mitigate the neuropathology of tinnitus.

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Section: The Role Of Autophagy In Maintaining the Structure Of Ohc Sc...mentioning

confidence: 99%

Section: Potential Benefits Of Nutraceuticalsmentioning

confidence: 99%

The Relevance of Autophagy within Inner Ear in Baseline Conditions and Tinnitus-Related Syndromes

Lazzeri,

Biagioni,

Ferrucci

et al. 2023

IJMS

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“…Razzuoli et al found that Cd could promote the expression of pro‐inflammatory cytokines in porcine epithelial cells, such as interleukin‐6 (IL‐6), IL‐8, and IL‐18 and transcription factors, such as NF‐κB, MYD88, and NF‐κB1 31 . In addition, metformin, a activator for AMPK, alleviates Cd‐stimulated degeneration of spiral ganglion neuron by restoring impaired autophagy flux, attenuating Cd‐induced apoptosis 32 . Furthermore, Cd promoted apoptosis of mouse kidney mesangial cells (MES13E cells) through cytoplasmic polyubiquitination of p53, which regulated by the polyubiquitination of SQSTM1/p62 (polyUb‐p62) and autophagy 33 …”

Section: Introductionmentioning

confidence: 99%

“…31 In addition, metformin, a activator for AMPK, alleviates Cd-stimulated degeneration of spiral ganglion neuron by restoring impaired autophagy flux, attenuating Cd-induced apoptosis. 32 Furthermore, Cd promoted apoptosis of mouse kidney mesangial cells (MES13E cells) through cytoplasmic polyubiquitination of p53, which regulated by the polyubiquitination of SQSTM1/p62 (polyUb-p62) and autophagy. 33 Recently, one metal biomaterial such as titanium dioxide nanoparticles (nTiO 2 ) have a different effect on Cd-or lead (Pb)-induced toxicity in human lung cells, which has the reinforced influence and has the prevented role, repectively.…”

Section: Introductionmentioning

confidence: 99%

Polystyrene exacerbates cadmium‐induced mitochondrial damage to lung by blocking autophagy in mice

Tong

Guo

et al. 2023

Environmental Toxicology

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Cadmium (Cd) is an environmental heavy metal, and its accumulation is harmful to animal and human health. The cytotoxicity of Cd includes oxidative stress, apoptosis, and mitochondrial histopathological changes. Furthermore, polystyrene (PS) is a kind of microplastic piece derived from biotic and abiotic weathering courses, and has toxicity in various aspects. However, the potential mechanism of action of Cd co-treated with PS is still poorly unclear. The objective of this study was to investigate the effects of PS on Cd-induced histopathological injury of mitochondria in the lung of mice. In this study, the results have showed that Cd could induce the activity of oxidative enzymes of the lung cells in mice, increasing the content of partial microelement and the phosphorylation of inflammatory factor NF-κB p65. Cd further destroys the integrity of mitochondria by increasing the expression of apoptotic protein and blocking the autophagy. In addition, PS solely group aggravated the lung damage in mice, especially mitochondrial toxicity, and played a synergistic effect with Cd in lung injury. However, how PS can augment mitochondrial damage and synergism with Cd in lung of mice requiring further exploration. Therefore, PS was able to exacerbate Cd-induced mitochondrial damage to the lung in mice by blocking autophagy, and was associated with the apoptosis.

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“…Studies have confirmed that the mitochondrial axis, specifically the binding of Dynamin‐related protein 1 (Drp1) to Retinoblastoma, can induce necroptosis in hepatocytes (Zhang et al, 2019). Additionally, studies have revealed Cd exposure can increase the risk of neurological disorders, such as memory deficits, degeneration of neurons and lipid accumulation in brain (da Costa et al, 2017; Daniel et al, 2004; Li, Wang, et al, 2022). As the largest immune organs of body, spleen is essential for further research on the specific mechanism of Cd exposure‐induced injury.…”

Section: Introductionmentioning

confidence: 99%

Cadmium exposure induces necroptosis of porcine spleen via ROS‐mediated activation of STAT1/RIPK3 signaling pathway

Lei

Zhang

et al. 2023

Environ and Mol Mutagen

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Cadmium (Cd), a heavy metal, is used in a wide range of applications, such as plastics, electroplating process, electronics, and so forth. Due to its bioaccumulation ability, Cd can contaminate soil, water, air and food. To determine the effect of Cd exposure on the necroptosis in pig spleen and its mechanistic investigation, we constructed a model in pigs by feeding them food containing 20 mg/kg Cd. In this study, we analyzed the effects of Cd exposure on pig spleen through HE staining, Quantitative real‐time PCR (qRT‐PCR), Western blot (WB), and principal component analysis (PCA). Results show that Cd exposure can destroy the structure and function of pig spleen, which is closely related to necroptosis. Further results show that Cd exposure can induce necroptosis through ROS‐mediated activation of Signal transducer and activator of transcription 1/Receptor‐Interacting Serine/Threonine‐Protein Kinase 3 (STAT1/RIPK3) signaling pathway in pig spleen. Additionally, Cd exposure also can affect the stability of mitochondrial‐associated endoplasmic reticulum membrane (MAMs) structure, which also contributes to the process of necroptosis. Our study provides insights into the physiological toxicity caused by Cd exposure.

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Metformin attenuates cadmium-induced degeneration of spiral ganglion neuron via restoring autophagic flux in primary culture

Cited by 6 publications

References 46 publications

The Relevance of Autophagy within Inner Ear in Baseline Conditions and Tinnitus-Related Syndromes

The Relevance of Autophagy within Inner Ear in Baseline Conditions and Tinnitus-Related Syndromes

Polystyrene exacerbates cadmium‐induced mitochondrial damage to lung by blocking autophagy in mice

Cadmium exposure induces necroptosis of porcine spleen via ROS‐mediated activation of STAT1/RIPK3 signaling pathway

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