Erdosteine protects HEI-OC1 auditory cells from cisplatin toxicity through suppression of inflammatory cytokines and induction of Nrf2 target proteins

Kim, Se Jin; Park, Channy; Lee, Joon No; Lim, Hye‐Won; Hong, Gi Yeon; Moon, Sangook; Lim, David J.; Choe, Seong Kyu; Park, Raekil

doi:10.1016/j.taap.2015.07.014

Cited by 29 publications

(15 citation statements)

References 60 publications

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“…In accordance with our results, several studies have shown that the activation of Nrf2 is associated with an accumulation of Nrf2 in the entire cell lysate [32,33,37,38] and that the release of Nrf2 from Keap1 repression by e.g., ROS leads to the stabilization and subsequent translocation of Nrf2 into the cell nucleus and to the activation of HO-1 transcription [39]. Regarding the demonstrated HO-1 induction by CBD, further investigations of our group have shown that this stimulation is not restricted to endothelial cells but also occurs in vascular smooth muscle cells [40] or in adipose-derived mesenchymal stem cells (unpublished results), whereby in the mentioned cell types, HO-1 induction was also registered in the presence of ∆ 9 -tetrahydrocannabinol (THC), which is another phytocannabinoid.…”

Section: Autophagysupporting

confidence: 93%

Cannabidiol Promotes Endothelial Cell Survival by Heme Oxygenase-1-Mediated Autophagy

Böckmann

Hinz

2020

Cells

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Cannabidiol (CBD), a non-psychoactive cannabinoid, has been reported to mediate antioxidant, anti-inflammatory, and anti-angiogenic effects in endothelial cells. This study investigated the influence of CBD on the expression of heme oxygenase-1 (HO-1) and its functional role in regulating metabolic, autophagic, and apoptotic processes of human umbilical vein endothelial cells (HUVEC). Concentrations up to 10 µM CBD showed a concentration-dependent increase of HO-1 mRNA and protein and an increase of the HO-1-regulating transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). CBD-induced HO-1 expression was not decreased by antagonists of cannabinoid-activated receptors (CB1, CB2, transient receptor potential vanilloid 1), but by the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC). The incubation of HUVEC with 6 µM CBD resulted in increased metabolic activity, while 10 µM CBD caused decreased metabolic activity and an induction of apoptosis, as demonstrated by enhanced caspase-3 cleavage. In addition, CBD triggered a concentration-dependent increase of the autophagy marker LC3A/B-II. Both CBD-induced LC3A/B-II levels and caspase-3 cleavage were reduced by NAC. The inhibition of autophagy by bafilomycin A1 led to apoptosis induction by 6 µM CBD and a further increase of the proapoptotic effect of 10 µM CBD. On the other hand, the inhibition of HO-1 activity with tin protoporphyrin IX (SnPPIX) or knockdown of HO-1 expression by Nrf2 siRNA was associated with a decrease in CBD-mediated autophagy and apoptosis. In summary, our data show for the first time ROS-mediated HO-1 expression in endothelial cells as a mechanism by which CBD mediates protective autophagy, which at higher CBD concentrations, however, can no longer prevent cell death inducing apoptosis.

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Section: Autophagysupporting

confidence: 93%

Cannabidiol Promotes Endothelial Cell Survival by Heme Oxygenase-1-Mediated Autophagy

Böckmann

Hinz

2020

Cells

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“…Recently, inflammatory damage is thought to contribute to the pathogenesis of cisplatin-induced ototoxicity37 and inhibition of pro-inflammatory cytokines significantly attenuates cisplatin-induced damage38. Moreover, mitochondrion is emerging as a critical signaling platform for the assembly of signalosomes regulating the apoptotic and inflammatory pathways39.…”

Section: Discussionmentioning

confidence: 99%

NLRX1 accelerates cisplatin-induced ototoxity in HEI-OC1 cells via promoting generation of ROS and activation of JNK signaling pathway

Yin

Sun

Yang

et al. 2017

Sci Rep

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Nucleotide-binding domain and leucine-rich-repeat-containing family member X1 (NLRX1), located in mitochondria, can recognize cytoplasmic pattern recognition receptors and is tightly related to reactive oxygen species (ROS) production, mitochondrial function, apoptosis and inflammation. The present study was designed to explore whether NLRX1 expresses in HEI-OC1 cells and, if so, to investigate the possible correlations between NLRX1 and cisplatin-induced ototoxity in vitro. Here, we report that NLRX1 was specifically localized to mitochondria in the cytoplasm of HEI-OC1 cells and its expression was increased concurrent with the increase of ROS production and occurrence of apoptosis in HEI-OC1 cells in response to cisplatin stimulus. NLRX1 overexpression led to a higher apoptosis in HEI-OC1 cells treated with cisplatin, whereas, NLRX silencing decreased cisplatin induced apoptosis. Mechanistic studies showed that NLRX1 activated mitochondrial apoptosis pathway as well as promoted ROS generation and JNK activation. Either inhibition of ROS generation or JNK signaling significantly prevented NLRX1-mediated mitochondrial apoptosis in HEI-OC1cells. In addition, NLRX1 expression was confirmed in cochlear explants. The findings from this work reveal that NLRX1 sensitizes HEI-OC1 cells to cisplatin-induced apoptosis via activation of ROS/JNK signaling pathway, suggesting that NLRX1 acts as an important regulator of the cisplatin-elicited ototoxity.

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“…Cisplatin (CP) or cis‐diamminedichloroplatin II is an inorganic platinum‐based antineoplastic drug used to treat solid tumors. However, its effectiveness is severely compromised due to neurotoxicity, hepatotoxicity, ototoxicity, nephrotoxicity, reproductive toxicity, and bone marrow suppression associated with its use . CP and most other platinum compounds induce damage to tumors via induction of apoptosis; mediated by signal transduction involving death receptor mechanisms as well as mitochondrial pathways.…”

Section: Introductionmentioning

confidence: 99%

Ellagic acid ameliorates cisplatin induced hepatotoxicity in colon carcinogenesis

Goyal

Koul

Ranawat

2019

Environmental Toxicology

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The clinical application of cisplatin (CP), one of the most extensively used antineoplastic drug, is restricted by its numerous side effects. CP's antitumor potential resides in the free generation of reactive oxygen species leading to oxidative stress. This stress is a source of the side effects associated with its use. Ellagic acid (EA), a polyphenol is known to possess multiple health benefits owing to its antioxidant properties. EA is largely metabolized by the colon microbiota of different mammals and therefore was a polyphenol of choice in the present study. The present study was thus carried out to explore the protective potential of EA on CP induced hepatotoxicity in colon tumor bearing mice. The administration of EA (10 mg/kg bwt po daily for 6 weeks) significantly ameliorated the toxicity caused by CP (5 mg/kg bwt ip once a week for 4 weeks). Activities of liver marker enzymes and lactate dehydrogenase were brought back to normal. EA cotreatment also led to a marked reduction in the extent of peroxidative damage to liver tissue as was evident from the improvement in the histopathological changes observed and FT‐IR analysis. The present study, therefore, suggests that the administration of EA reduces the CP‐induced hepatotoxicity, thereby emerging out as a potential candidate for chemopreventive action.

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Erdosteine protects HEI-OC1 auditory cells from cisplatin toxicity through suppression of inflammatory cytokines and induction of Nrf2 target proteins

Cited by 29 publications

References 60 publications

Cannabidiol Promotes Endothelial Cell Survival by Heme Oxygenase-1-Mediated Autophagy

Cannabidiol Promotes Endothelial Cell Survival by Heme Oxygenase-1-Mediated Autophagy

NLRX1 accelerates cisplatin-induced ototoxity in HEI-OC1 cells via promoting generation of ROS and activation of JNK signaling pathway

Ellagic acid ameliorates cisplatin induced hepatotoxicity in colon carcinogenesis

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