Melatonin inhibits the apoptosis of rooster Leydig cells by suppressing oxidative stress via AKT-Nrf2 pathway activation

2020 ◽  
Vol 160 ◽  
pp. 1-12
Author(s):  
Yangyunyi Dong ◽  
Jing Zhao ◽  
Qingyu Zhu ◽  
Hongyu Liu ◽  
Jun Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Leydig Cells ◽  
Nrf2 Pathway ◽  
Pathway Activation

scholarly journals Proanthocyanidins-Mediated Nrf2 Activation Ameliorates Glucocorticoid-Induced Oxidative Stress and Mitochondrial Dysfunction in Osteoblasts

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Liang Chen ◽  
Sun-Li Hu ◽  
Jun Xie ◽  
De-Yi Yan ◽  
She-Ji Weng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Low Dose ◽  
Distal Femur ◽  
Therapeutic Potential ◽  
Protective Effects ◽  
Nrf2 Pathway ◽  
Pathway Activation ◽  
Nrf2 Activation ◽  
Osteoblast Apoptosis

The widespread use of therapeutic glucocorticoids has increased the frequency of glucocorticoid-induced osteoporosis (GIOP). One of the potential pathological processes of GIOP is an increased level of oxidative stress and mitochondrial dysfunction, which eventually leads to osteoblast apoptosis. Proanthocyanidins (PAC) are plant-derived antioxidants that have therapeutic potential against GIOP. In our study, a low dose of PAC was nontoxic to healthy osteoblasts and restored osteogenic function in dexamethasone- (Dex-) treated osteoblasts by suppressing oxidative stress, mitochondrial dysfunction, and apoptosis. Mechanistically, PAC neutralized Dex-induced damage in the osteoblasts by activating the Nrf2 pathway, since silencing Nrf2 partly eliminated the protective effects of PAC. Furthermore, PAC injection restored bone mass and promoted the expression of Nrf2 in the distal femur of Dex-treated osteoporotic rats. In summary, PAC protect osteoblasts against Dex-induced oxidative stress and mitochondrial dysfunction via the Nrf2 pathway activation and may be a promising drug for treating GIOP.

scholarly journals Activation of the NRF2 pathway in Keap1-knockdown mice attenuates progression of age-related hearing loss

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Tetsuya Oishi ◽  
Daisuke Matsumaru ◽  
Nao Ota ◽  
Hiroshi Kitamura ◽  
Tianxiang Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hearing Loss ◽  
Target Genes ◽  
Negative Regulator ◽  
Nrf2 Pathway ◽  
Expression Levels ◽  
Age Related ◽  
Pathway Activation ◽  
Brainstem Response ◽  
Age Related Hearing Loss

AbstractAge-related hearing loss (AHL) is a progressive sensorineural hearing loss in elderly people. Although no prevention or treatments have been established for AHL, recent studies have demonstrated that oxidative stress is closely related to pathogenesis of AHL, suggesting that suppression of oxidative stress leads to inhibition of AHL progression. NRF2 is a master transcription factor that regulates various antioxidant proteins and cytoprotection factors. To examine whether NRF2 pathway activation prevents AHL, we used Keap1-knockdown (Keap1FA/FA) mice, in which KEAP1, a negative regulator of NRF2, is decreased, resulting in the elevation of NRF2 activity. We compared 12-month-old Keap1FA/FA mice with age-matched wild-type (WT) mice in the same breeding colony. In the Keap1FA/FA mice, the expression levels of multiple NRF2 target genes were verified to be significantly higher than the expression levels of these genes in the WT mice. Histological analysis showed that cochlear degeneration at the apical and middle turns was ameliorated in the Keap1FA/FA mice. Auditory brainstem response (ABR) thresholds in the Keap1FA/FA mice were significantly lower than those in the WT mice, in particular at low–mid frequencies. Immunohistochemical detection of oxidative stress markers suggested that oxidative stress accumulation was attenuated in the Keap1FA/FA cochlea. Thus, we concluded that NRF2 pathway activation protects the cochlea from oxidative damage during aging, in particular at the apical and middle turns. KEAP1-inhibiting drugs and phytochemicals are expected to be effective in the prevention of AHL.

scholarly journals A Protein from Dioscorea polystachya (Chinese Yam) Improves Hydrocortisone-Induced Testicular Dysfunction by Alleviating Leydig Cell Injury via Upregulation of the Nrf2 Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Shiting Yu ◽  
Bing Han ◽  
Xin Xing ◽  
Yixuan Li ◽  
Daqing Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Leydig Cell ◽  
Leydig Cells ◽  
Cell Injury ◽  
Nrf2 Pathway ◽  
Chinese Yam ◽  
Testicular Dysfunction ◽  
Tgf Β1

Leydig cell injury has been described as a primary driver of testicular dysfunction and is affected by oxidative stress. Dioscorea polystachya (Chinese yam) is used to improve testicular dysfunction in clinical and pharmacological research via its antioxidative activity, but the mechanisms underlying the beneficial effect of Chinese yam on testicular dysfunction and its suppression of Leydig cell oxidative damage remain unclear. In this study, we obtained a Chinese yam protein (DP1) and explored its effectiveness and possible mechanism in improving testicular dysfunction in vivo and in vitro. We established a testicular dysfunction model in rats using hydrocortisone (HCT). DP1 increased body weight and organ index, improved the deterioration in testicular morphology (including increasing the diameter of seminiferous tubules and thickness of germinal cell layers, inhibiting testicular cell apoptosis by increasing the Bcl-2/Bax ratio, and impeding collagen leakage by downregulating TGF-β1 and p-SMAD2/3 expression), and restored the testosterone content. In addition, DP1 enhanced the number of Leydig cells in rats and H2O2-induced TM3 Leydig cells, and the effect of DP1 on the apoptosis, fibrosis, and testosterone content of TM3 cells was similar to that observed in vivo. These changes were dependent on the regulation of oxidative stress, including significantly reduced intracellular 8-hydroxy-2-deoxyguanosine levels, enhanced superoxide dismutase activities, and decreased superoxide anion levels, which were confirmed via a superoxide overexpression system. Furthermore, we observed that DP1 promoted Nrf2 nuclear import and upregulated antioxidant factor expression in vivo and in vitro. However, Nrf2 silencing eliminated the ability of DP1 to increase the Bcl-2/Bax ratio, reduce the expression levels of TGF-β1 and p-SMAD2/3, and increase testosterone contents in H2O2-induced TM3 cells. In conclusion, DP1 reversed the HCT-induced testicular apoptosis and fibrosis and decreased testosterone contents by alleviating Leydig cell oxidative damage via upregulation of the Nrf2 pathway.

Sargentgloryvine Stem Water Extract Mediated Nrf2 Pathway Activation and HO-1 Upregulation

2017 ◽  
Vol 27 (4) ◽  
pp. 27
Author(s):  
Zhaorong CHEN ◽  
Xiaoping CHENG ◽  
Jianfeng CHU ◽  
Jun PENG ◽  
Wei LIN
Keyword(s):  
Water Extract ◽  
Nrf2 Pathway ◽  
Pathway Activation ◽  
Stem Water

scholarly journals Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis

2021 ◽  
Vol 16 (1) ◽  
pp. 537-543
Author(s):  
Mei Zhang ◽  
Jing Yuan ◽  
Rong Dong ◽  
Jingjing Da ◽  
Qian Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Tubular Injury ◽  
Jnk Pathway ◽  
Pathway Activation

Abstract Background Hyperhomocysteinemia (HHcy) plays an important role in the progression of many kidney diseases; however, the relationship between HHcy and ischemia-reperfusion injury (IRI)-induced acute kidney injury (IRI-induced AKI) is far from clear. In this study, we try to investigate the effect and possible mechanisms of HHcy on IRI-induced AKI. Methods Twenty C57/BL6 mice were reared with a regular diet or high methionine diet for 2 weeks (to generate HHcy mice); after that, mice were subgrouped to receive sham operation or ischemia-reperfusion surgery. Twenty four hour after reperfusion, serum creatinine, blood urea nitrogen, and Malondialdehyde (MDA) were measured. H&E staining for tubular injury, western blot for γH2AX, JNK, p-JNK, and cleaved caspase 3, and TUNEL assay for tubular cell apoptosis were also performed. Results Our results showed that HHcy did not influence the renal function and histological structure, as well as the levels of MDA, γH2AX, JNK, p-JNK, and tubular cell apoptosis in control mice. However, in IRI-induced AKI mice, HHcy caused severer renal dysfunction and tubular injury, higher levels of oxidative stress, DNA damage, JNK pathway activation, and tubular cell apoptosis. Conclusion Our results demonstrated that HHcy could exacerbate IRI-induced AKI, which may be achieved through promoting oxidative stress, DNA damage, JNK pathway activation, and consequent apoptosis.

scholarly journals Salvianolic Acid B Prevents Iodinated Contrast Media-Induced Acute Renal Injury in Rats via the PI3K/Akt/Nrf2 Pathway

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Liu Tongqiang ◽  
Liu Shaopeng ◽  
Yu Xiaofang ◽  
Song Nana ◽  
Xu Xialian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Contrast Media ◽  
Renal Injury ◽  
Salvianolic Acid B ◽  
Pi3k Inhibitor ◽  
Iodinated Contrast Media ◽  
Acute Renal Injury ◽  
Nrf2 Pathway ◽  
Salvianolic Acid ◽  
Iodinated Contrast

Contrast-induced acute renal injury (CI-AKI) has become a common cause of hospital-acquired renal failure. However, the development of prophylaxis strategies and approved therapies for CI-AKI is limited. Salvianolic acid B (SB) can treat cardiovascular-related diseases. The aim of the present study was to assess the effect of SB on prevention of CI-AKI and explore its underlying mechanisms. We examined its effectiveness of preventing renal injury in a novel CI-AKI rat model. Compared with saline, intravenous SB pretreatment significantly attenuated elevations in serum creatinine and the histological changes of renal tubular injuries, reduced the number of apoptosis-positive tubular cells, activated Nrf2, and lowered the levels of renal oxidative stress induced by iodinated contrast media. The above renoprotection of SB was abolished by the PI3K inhibitor (wortmannin). In HK-2 cells, SB activated Nrf2 and decreased the levels of oxidative stress induced by hydrogen peroxide and subsequently improved cell viability. The above cytoprotection of SB was blocked by the PI3K inhibitor (wortmannin) or siNrf2. Thus, our results demonstrate that, due to its antioxidant properties, SB has the potential to effectively prevent CI-AKI via the PI3K/Akt/Nrf2 pathway.

scholarly journals Keap1/Nrf2 pathway activation leads to a repressed hepatic gluconeogenic and lipogenic program in mice on a high-fat diet

2016 ◽  
Vol 591 ◽  
pp. 57-65 ◽  
Author(s):  
Stephen L. Slocum ◽  
John J. Skoko ◽  
Nobunao Wakabayashi ◽  
Susan Aja ◽  
Masayuki Yamamoto ◽  
...  
Keyword(s):  
High Fat Diet ◽  
High Fat ◽  
Nrf2 Pathway ◽  
Pathway Activation

scholarly journals Antioxidant Therapy in Pancreatitis

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 657
Author(s):  
Lourdes Swentek ◽  
Dean Chung ◽  
Hirohito Ichii
Keyword(s):  
Oxidative Stress ◽  
Chronic Pancreatitis ◽  
Total Pancreatectomy ◽  
Current Status ◽  
Related Factor ◽  
Endocrine Dysfunction ◽  
Deep Dive ◽  
Pathway Activation ◽  
Advanced Therapies ◽  
And Oxidative Stress

Pancreatitis is pathologic inflammation of the pancreas characterized by acinar cell destruction and oxidative stress. Repeated pancreatic insults can result in the development of chronic pancreatitis, characterized by irreversible fibrosis of the pancreas and many secondary sequelae, ultimately leading to the loss of this important organ. We review acute pancreatitis, chronic pancreatitis, and pancreatitis-related complications. We take a close look at the pathophysiology with a focus on oxidative stress and how it contributes to the complications of the disease. We also take a deep dive into the evolution and current status of advanced therapies for management including dietary modification, antioxidant supplementation, and nuclear factor erythroid-2-related factor 2-Kelch-like ECH-associated protein 1(Nrf2-keap1) pathway activation. In addition, we discuss the surgeries aimed at managing pain and preventing further endocrine dysfunction, such as total pancreatectomy with islet auto-transplantation.

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