scholarly journals Hsp70/Bmi1-FoxO1-SOD Signaling Pathway Contributes to the Protective Effect of Sound Conditioning against Acute Acoustic Trauma in a Rat Model

2020 ◽  
Vol 2020 ◽  
pp. 1-22
Author(s):  
Guoxia Zhu ◽  
Yongxiang Wu ◽  
Yang Qiu ◽  
Keyong Tian ◽  
Wenjuan Mi ◽  
...  
Keyword(s):  
Protective Effect ◽  
Signaling Pathway ◽  
Rat Model ◽  
Molecular Mechanisms ◽  
Outer Hair Cell ◽  
Acoustic Trauma ◽  
Auditory Brainstem Responses ◽  
Ultrastructural Changes ◽  
Ganglion Neurons ◽  
Acute Acoustic Trauma

Sound conditioning (SC) is defined as “toughening” to lower levels of sound over time, which reduces a subsequent noise-induced threshold shift. Although the protective effect of SC in mammals is generally understood, the exact mechanisms involved have not yet been elucidated. To confirm the protective effect of SC against noise exposure (NE) and the stress-related signaling pathway of its rescue, we observed target molecule changes caused by SC of low frequency prior to NE as well as histology analysis in vivo and verified the suggested mechanisms in SGNs in vitro. Further, we investigated the potential role of Hsp70 and Bmi1 in SC by targeting SOD1 and SOD2 which are regulated by the FoxO1 signaling pathway based on mitochondrial function and reactive oxygen species (ROS) levels. Finally, we sought to identify the possible molecular mechanisms associated with the beneficial effects of SC against noise-induced trauma. Data from the rat model were evaluated by western blot, immunofluorescence, and RT-PCR. The results revealed that SC upregulated Hsp70, Bmi1, FoxO1, SOD1, and SOD2 expression in spiral ganglion neurons (SGNs). Moreover, the auditory brainstem responses (ABRs) and electron microscopy revealed that SC could protect against acute acoustic trauma (AAT) based on a significant reduction of hearing impairment and visible reduction in outer hair cell loss as well as ultrastructural changes in OHCs and SGNs. Collectively, these results suggested that the contribution of Bmi1 toward decreased sensitivity to noise-induced trauma following SC was triggered by Hsp70 induction and associated with enhancement of the antioxidant system and decreased mitochondrial superoxide accumulation. This contribution of Bmi1 was achieved by direct targeting of SOD1 and SOD2, which was regulated by FoxO1. Therefore, the Hsp70/Bmi1-FoxO1-SOD signaling pathway might contribute to the protective effect of SC against AAT in a rat model.

scholarly journals Reduced Formation of Oxidative Stress Biomarkers and Migration of Mononuclear Phagocytes in the Cochleae of Chinchilla after Antioxidant Treatment in Acute Acoustic Trauma

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Xiaoping Du ◽  
Chul-Hee Choi ◽  
Kejian Chen ◽  
Weihua Cheng ◽  
Robert A. Floyd ◽  
...  
Keyword(s):  
Hair Cell ◽  
Outer Hair Cell ◽  
Acoustic Trauma ◽  
Mononuclear Phagocytes ◽  
Auditory Brainstem Responses ◽  
Sensory Cells ◽  
Antioxidant Treatment ◽  
Cell Counts ◽  
And Migration ◽  
Acute Acoustic Trauma

Objective. Inhibition of inflammation and free radical formation in the cochlea may be involved in antioxidant treatment in acute acoustic trauma.Procedure. Chinchilla were exposed to 105 dB sound pressure level octave band noise for 6 hours. One group of chinchilla was treated with antioxidants after noise exposure. Auditory brainstem responses, outer hair cell counts, and immunohistochemical analyses of biomarkers in the cochlea were conducted.Results. The antioxidant treatment significantly reduced hearing threshold shifts, outer hair cell loss, numbers of CD45+cells, as well as 4-hydroxy-2-nonenal and nitrotyrosine formation in the cochlea.Conclusion. Antioxidant treatment may provide protection to sensory cells by inhibiting formation of reactive oxygen and nitrogen products and migration of mononuclear phagocytes in the cochlea. The present study provides further evidence of effectiveness of antioxidant treatment in reducing permanent hearing loss.

scholarly journals Protective effect of Nigella sativa oil on acoustic trauma induced hearing loss in rats

2017 ◽  
Vol 7 (2) ◽  
Author(s):  
Belde Culhaoglu ◽  
Selim S. Erbek ◽  
Seyra Erbek ◽  
Evren Hizal
Keyword(s):  
Hearing Loss ◽  
Protective Effect ◽  
Nigella Sativa ◽  
Acoustic Trauma ◽  
Female Rats ◽  
Auditory Brainstem Responses ◽  
Control Group ◽  
Study Group ◽  
Intensity Level ◽  
Hearing Thresholds

Acoustic trauma is a common reason for hearing loss. Different agents are used to prevent the harmful effect of acoustic trauma on hearing. The aim of this study was to evaluate the potential preventive effect of <em>Nigella sativa</em> (black cumin) oil in acoustic trauma. Our experimental study was conducted with 20 Sprague Downey female rats (mean age, 12 months; mean weight 250 g). All of the procedures were held under general anesthesia. Following otoscopic examinations, baseline-hearing thresholds were obtained using auditory brainstem responses (ABR). To create acoustic trauma, the rats were then exposed to white band noise of 4 kHz with an intensity level of 107 dB in a soundproof testing room. On Day 1 following acoustic trauma, hearing threshold measurements were repeated. The rats were divided into two groups as the study group (n: 10) and the controls (n: 10). 2 mL/kg/day of <em>Nigella sativa</em> oil was given to the rats in the study group orally. On Day 4 following acoustic trauma, ABR measurements were repeated again. There was no difference between the baseline hearing thresholds of the rats before acoustic trauma (P&gt;0.005). After the acoustic trauma, hearing thresholds were increased and there was no significant statistically difference between the hearing thresholds of the study and control groups (P=0.979). At the 4<sup>th</sup> day following acoustic trauma, hearing thresholds of the rats in control group were found to be higher than those in the study group (P=0.03). Our results suggest that <em>Nigella sativa</em> oil has a protective effect against acoustic trauma in early period. This finding should be supported with additional experimental and clinical studies, especially to determine the optimal dose, duration and frequency of potential <em>Nigella sativa</em> oil therapy.

scholarly journals Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway

Toxins ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 794
Author(s):  
Chenxi Luo ◽  
Chenglong Huang ◽  
Lijuan Zhu ◽  
Li Kong ◽  
Zhihang Yuan ◽  
...  
Keyword(s):  
Protective Effect ◽  
Antioxidant Capacity ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Betulinic Acid ◽  
Molecular Mechanisms ◽  
Mucosal Barrier ◽  
Intestinal Damage ◽  
Trichothecene Mycotoxin ◽  
Anti Inflammatory

T-2 toxin, a trichothecene mycotoxin produced by Fusarium, is widely distributed in crops and animal feed and frequently induces intestinal damage. Betulinic acid (BA), a plant-derived pentacyclic lupane-type triterpene, possesses potential immunomodulatory, antioxidant and anti-inflammatory biological properties. The current study aimed to explore the protective effect and molecular mechanisms of BA on intestinal mucosal impairment provoked by acute exposure to T-2 toxin. Mice were intragastrically administered BA (0.25, 0.5, or 1 mg/kg) daily for 2 weeks and then injected intraperitoneally with T-2 toxin (4 mg/kg) once to induce an intestinal impairment. BA pretreatment inhibited the loss of antioxidant capacity in the intestine of T-2 toxin-treated mice by elevating the levels of CAT, GSH-PX and GSH and reducing the accumulation of MDA. In addition, BA pretreatment alleviated the T-2 toxin-triggered intestinal immune barrier dysregulation by increasing the SIgA level in the intestine at dosages of 0.5 and 1 mg/kg, increasing IgG and IgM levels in serum at dosages of 0.5 and 1 mg/kg and restoring the intestinal C3 and C4 levels at a dosage of 1 mg/kg. BA administration at a dosage of 1 mg/kg also improved the intestinal chemical barrier by decreasing the serum level of DAO. Moreover, BA pretreatment improved the intestinal physical barrier via boosting the expression of ZO-1 and Occludin mRNAs and restoring the morphology of intestinal villi that was altered by T-2 toxin. Furthermore, treatment with 1 mg/kg BA downregulated the expression of p-NF-κB and p-IκB-α proteins in the intestine, while all doses of BA suppressed the pro-inflammatory cytokines expression of IL-1β, IL-6 and TNF-α mRNAs and increased the anti-inflammatory cytokine expression of IL-10 mRNA in the intestine of T-2 toxin-exposed mice. BA was proposed to exert a protective effect on intestinal mucosal disruption in T-2 toxin-stimulated mice by enhancing the intestinal antioxidant capacity, inhibiting the secretion of inflammatory cytokines and repairing intestinal mucosal barrier functions, which may be associated with BA-mediated inhibition of the NF-κB signaling pathway activation.

Protective Effect of Carnosine on Excitable Structures of the Auditory Apparatus in Albino Rats with Acute Acoustic Trauma

2004 ◽  
Vol 137 (1) ◽  
pp. 98-102 ◽  
Author(s):  
S. G. Zhuravskii ◽  
L. A. Aleksandrova ◽  
S. A. Ivanov ◽  
V. S. Sirot ◽  
A. I. Lopotko ◽  
...  
Keyword(s):  
Protective Effect ◽  
Acoustic Trauma ◽  
Albino Rats ◽  
Acute Acoustic Trauma

Molecular mechanisms involved in the protective effect of the chloroform extract of Selaginella lepidophylla (Hook. et Grev.) Spring in a lithiasic rat model

Urolithiasis ◽  
2013 ◽  
Vol 41 (3) ◽  
pp. 205-215 ◽  
Author(s):  
Estévez-Carmona María Mirian ◽  
Narvaéz-Morales Juanita ◽  
Barbier Olivier Christophe ◽  
Meléndez-Camargo María Estela
Keyword(s):  
Protective Effect ◽  
Rat Model ◽  
Molecular Mechanisms ◽  
Chloroform Extract ◽  
Selaginella Lepidophylla

scholarly journals Transcriptomics‐based analysis of the mechanism by which Wang-Bi capsule alleviates joint destruction in rats with collagen‐induced arthritis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Haiyang Shu ◽  
Hanxiao Zhao ◽  
Yingjie Shi ◽  
Cheng Lu ◽  
Li Li ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Joint Destruction ◽  
Micro Ct ◽  
Collagen Induced Arthritis ◽  
Cartilage Development ◽  
And Cartilage

Abstract Background Rheumatoid arthritis (RA) is a chronic autoimmune disease accompanied with joint destruction that often leads to disability. Wang-Bi capsule (WB), a traditional Chinese medicine-based herbs formula, has exhibited inhibition effect on joint destruction of collagen-induced arthritis (CIA) animal model in our previous study. But its molecular mechanisms are still obscure. Methods CIA rats were treated intragastrical with WB for eight weeks, and the effect of joints protection were evaluated by hematoxylin and eosin (H&E) staining, safranin O fast green staining, tartrate-resistant acid phosphatase (TRAP) staining and micro‑CT scanning analysis. The transcriptomic of tarsal joints were used to investigate how WB alleviated joint destruction. Results The histological examination of ankle joints showed WB alleviated both cartilage damage and bone destruction of CIA rats. This protective effect on joints were further evidenced by micro-CT analysis. The transcriptomic analysis showed that WB prominently changed 12 KEGG signaling pathways (“calcium signaling pathway”, “cAMP signaling pathway”, “cell adhesion molecules”, “chemokine signaling pathway”, “complement and coagulation cascades”, “MAPK signaling pathway”, “NF-kappa B signaling pathway”, “osteoclast differentiation”, “PI3K-Akt signaling pathway”, “focal adhesion”, “Gap junction” and “Rap1 signaling pathway”) associated with bone or cartilage. Several genes (including Il6, Tnfsf11, Ffar2, Plg, Tnfrsf11b, Fgf4, Fpr1, Siglec1, Vegfd, Cldn1, Cxcl13, Chad, Arrb2, Fgf9, Egfr) regulating bone resorption, bone formation and cartilage development were identified by further analysis. Meanwhile, these differentially expressed genes were validated by real-time quantitative PCR. Conclusions Overall, the protective effect of WB treatment on joint were confirmed in CIA rats, and its basic molecular mechanisms may be associated with regulating some genes (including Il6, Tnfsf11, Ffar2 and Plg etc.) involved in bone resorption, bone formation and cartilage development.

Protective Effect of Swertiamarin on Myocardial Injury Through Activation of Nrf2/HO-1 Pathway in Heart Failure Model of Rats

2020 ◽  
Vol 18 (3) ◽  
pp. 260-265
Author(s):  
Xu Lin ◽  
Zheng Xiaojun ◽  
Lv Heng ◽  
Mo Yipeng ◽  
Tong Hong
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Protective Effect ◽  
Infarct Size ◽  
Rat Model ◽  
Left Ventricular ◽  
Related Factor ◽  
Nuclear Factor ◽  
Internal Dimension

The purpose of this study was to evaluate the protective effect of swertiamarin on heart failure. To this end, a rat model of heart failure was established via left coronary artery ligation. Infarct size of heart tissues was determined using triphenyl tetrazolium chloride staining. Echocardiography was performed to evaluate cardiac function by the determination of ejection fraction, left ventricular internal dimension in diastole and left ventricular internal dimension in systole. The effect of swertiamarin on oxidative stress was evaluated via enzyme-linked immunosorbent assay. The mechanism was evaluated using western blot. Administration of swertiamarin reduced the infarct size of heart tissues in rat models with heart failure. Moreover, swertiamarin treatment ameliorated the cardiac function, increased ejection fraction and fractional shortening, decreased left ventricular internal dimension in diastole and left ventricular internal dimension in systole. Swertiamarin improved oxidative stress with reduced malondialdehyde, while increased superoxide dismutase, glutathione, and GSH peroxidase. Furthermore, nuclear-factor erythroid 2-related factor 2, heme oxygenase and NAD(P)H dehydrogenase (quinone 1) were elevated by swertiamarin treatment in heart tissues of rat model with heart failure. Swertiamarin alleviated heart failure through suppression of oxidative stress response via nuclear-factor erythroid 2-related factor 2/heme oxygenase-1 pathway providing a novel therapeutic strategy for heart failure.

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