POULTRY SCIENCE
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2025
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IF 4.2
Yulong Li,Shu Wang,Rui Feng
Cadmium (Cd) is a non-essential heavy metal that is highly toxic to testicle. Selenium (Se) is known to possess antagonistic effects against Cd toxicity, yet the precise mechanisms through which Se counteracts Cd-induced testicular damage in chickens through Nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathway, oxidative stress (OS), apoptosis, and inflammation remained unclear. In the present study, the experimental model of chicken testis was established by incorporating CdCl 2 and Na 2 SeO 3 into the dietary intake. After 60 days, chickens from each group were euthanized, and testicular and serum samples were subsequently collected. Ultrastructural assessment revealed that Se supplementation significantly mitigated the testicular damage induced by Cd. Se effectively suppressed the Cd-induced elevation in ROS, MDA, and H 2 O 2 levels, while also preventing the downregulation of CAT, GSH, and T-AOC levels. Furthermore, Se administration ameliorated the reduction in the expression levels of Nrf2, HO-1, and Bcl-2 induced by Cd, and counteracted the overexpression of Caspase-3, Bax, Cyt-c, and Caspase-9, TNF-α, IL-2, IL-6, and IL-1β. Meanwhile, immunofluorescence data demonstrated that Se attenuated the Cd-induced decrease in Nrf2 and HO-1 expression and the upregulation of IL-6 expression. In conclusion, this study elucidated that Se might mitigate Cd-induced oxidative stress in chicken testicles through the stimulation of the Nrf2/HO-1 signaling pathway, thereby inhibiting apoptosis and inflammation, and was beneficial in reducing Cd-induced testicular injury.
研究领域:
毒理学
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生殖生物学
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营养学
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PubMed
高影响因子
CELL BIOLOGY INTERNATIONAL
·
2022
·Vol. 47
·期 3
·598-611
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IF 4.473
Yangyang Wu,Shuo Zhou,An Zhao,Yuling Mi,Caiqiao Zhang
Oxidative stress is a major cause of ovarian aging and follicular atresia. There is growing evidence that showed potential roles of rutin in antidiabetic, anti-inflammatory, antitumor, antibacterial and antioxidant, although it is yet unclear what the underlying mechanism is. Here, we looked into the potential effects of rutin on oxidative stress in the prehierarchical small white follicles (SWFs) from 580-day-old (D580) laying chickens. According to the findings, aging D580 layer ferroptosis was much higher than it was for laying hens during the peak period (280-day-old, D280). In both naturally aged and d -gal-induced chicken SWFs, rutin treatment concurrently boosted cell proliferation and prevented apoptosis. In addition, rutin inhibited the increased ferroptosis in aging hens. Meanwhile, rutin markedly suppressed the elevated ferroptosis and descending antioxidant capacity of D280-culture-SWFs from chicken elicited by d -gal. Rutin's activation of the Nrf2/HO-1 pathway hastened the SWFs' verbal battle with oxidative damage and reduced ferroptosis. Furthermore, activation of the ferroptosis signal increased the oxidative damage in SWFs. In conclusion, rutin alleviated oxidative stress that was induced by ferroptosis in aging chicken SWFs through Nrf2/HO-1 pathway. These findings point to a novel mechanism by which rutin protects SWFs from oxidative stress by suppressing ferroptosis, which is presumably a fresh approach to slowing ovarian aging in laying hens.
研究领域:
动物科学
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分子生物学
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营养学
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PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2025
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IF 3.5
Ziyang Huang,Ruijia Xu,Zhongjun Wan,Chao Liu,Jinquan Li,Jun He,Li Li
Cadmium (Cd) is a prevalent heavy metal pollutant known to cause lung damage. However, the mechanisms underlying Cd-induced lung injury and the associated therapeutic strategies remain unclear. By establishing Cd-induced lung damage models both in vivo and in vitro , we observed that Cd inhibited the Nrf2/HO-1 signaling pathway, disrupted the redox balance in lung tissue, accelerated endoplasmic reticulum (ER) stress, and promoted ferroptosis, ultimately leading to lung injury. Melatonin (Mel), a potent reactive oxygen species (ROS) inhibitor with high antioxidative efficacy, mitigated the increasing in ROS and the decreasing in superoxide dismutase levels induced by Cd, as well as the upregulation of PERK-eIF2α-ATF4 signaling associated with ER stress, through the activation of the Nrf2/HO-1 signaling pathway. Furthermore, Mel administration not only prevented Cd-induced iron overload but also reduced lipid peroxidation levels, thereby improving mitochondrial morphological alterations. Collectively, our results demonstrated that Mel treatment alleviated Cd-induced lung injury by inhibiting oxidative stress, which in turn ameliorated ER stress and ferroptosis through the activation of the Nrf2/HO-1 pathway.
研究领域:
毒理学
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分子生物学
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呼吸系统医学
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PubMed
高影响因子
HISTOCHEMISTRY AND CELL BIOLOGY
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2025
·Vol. 163
·期 1
·1-15
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IF 2.1
Zhong Wen-Jing,Xiong Jian-Bing,Zhang Chen-Yu,Jin Ling,Yang Nan-Shi-Yu,Sha Han-Xi,Liu Yu-Biao,Duan Jia-Xi,Guan Cha-Xiang,Zhou Yong,Su Feng
Pulmonary fibrosis (PF) is an insidious, progressive, and fatal age-associated disease that occurs primarily in older adults and has a poor prognosis. Alveolar epithelial cell (AEC) senescence is the critical pathological mechanism of PF. The accumulation of oxygen radicals, commonly referred to as reactive oxygen species (ROS), strongly contributes to cellular senescence. The triggering receptor expressed on myeloid cells-1 (TREM-1) is a pattern recognition receptor. Triggering via TREM-1 results in ROS, leading to the amplification of inflammation. However, whether TREM-1 is involved in PF by inducing oxidative stress to exacerbate AEC senescence remains unclear. We first observed that blockade of TREM-1 during the fibrotic phase attenuated bleomycin (BLM)-induced PF in mice, with decreased expression of senescence-related proteins, including p16, p21, p53, and γ-H2AX, in the lung tissue. Moreover, TREM-1 blockade during the fibrosis stage restored antioxidant levels by increasing the percentage of Nrf2- and HO-1-positive cells in mice with PF. Notably, TREM-1 was highly expressed in surfactant-associated protein (SPC)-positive AECs in mice with PF. In vitro, blocking TREM-1 activated Nrf2 antioxidant signaling, thereby decreasing intracellular ROS levels and diminishing BLM-induced senescence in AECs. Furthermore, inhibition of Nrf2/HO-1 partially counteracted the anti-senescence effect of blocking TREM-1 in BLM-treated AECs. In this study, we reported that TREM-1 stimulated the senescence of AECs, induced ROS and exacerbated PF. We also provide compelling evidence suggesting that the Nrf2/HO-1 signaling pathway underpins TREM-1-triggered senescence. Therefore, our findings provide new insights into the molecular mechanisms associated with TREM-1 and AEC senescence in the pathogenesis of PF.
研究领域:
医学
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分子生物学
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PubMed
高影响因子
Translational Cancer Research
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2025
·Vol. 14
·期 11
·7641
·
IF 1.7
Yuan Cheng,Liu Ruiwen,Xu Xinming,Sun Jun,Zhu Yi,Lu Rongzhu,Liu Yueyu,Chen Jian
Background Because of the high malignancy and subtle early symptoms of hepatocellular carcinoma (HCC), most patients lose the opportunity for surgery and opt for drug therapy. However, the current drugs for HCC treatment remain suboptimal, underscoring the urgent need to develop a novel anti-HCC agent. Curcumin is a natural chemical compound that has anti-cancer effects on various tumor cells, attracting sustained attention from researchers and clinicians. The present study aims to further elucidate curcumin’s anti-HCC mechanisms, thereby offering a promising therapeutic candidate for HCC patients. Methods The viability of HCC cells was evaluated by Cell Counting Kit-8 (CCK-8) assay. The levels of glutathione (GSH), malondialdehyde (MDA), and total iron in the cells were detected by biochemical kits. The levels of reactive oxygen species (ROS) and Fe 2+ in the cells were detected by fluorescent probes. The protein expressions of protein kinase RNA-like endoplasmic reticulum kinase (PERK), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutathione peroxidase 4 (GPX4) in the cells were detected by western blotting. Results Curcumin exerted a notably suppressive impact on HCC cells, which could be reversed by ferrostatin-1 (Fer-1) and desferrioxamine (DFO). By detecting cellular metabolic products, we observed an increase in total iron, Fe 2+ , MDA, ROS, and a reduction in GSH levels in HCC cells after treatment with curcumin, and these effects could be attenuated by Fer-1. Western blot analysis showed that curcumin significantly downregulated GPX4 levels in HCC cells while upregulating PERK, Nrf2 and HO-1 expression. Additionally, using PERK inhibitor, HO-1 inhibitor, and endoplasmic reticulum (ER) stress inhibitor could partially reverse the inhibition of HCC cells viability by curcumin and alleviate the reduction of GPX4 expression caused by curcumin. Conclusions Curcumin may induce ferroptosis in HCC cells through the PERK/Nrf2/HO-1 signaling pathway, thereby exerting its anti-cancer effects, suggesting that curcumin could potentially be used as a drug for treating HCC.
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高影响因子
Frontiers in Pharmacology
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2022
·
IF 5.988
Li Dafei,Zhao Haiyan,Xu Piao,Lin Qiongping,Zhao Tingting,Li Chubing,Cui Zhong-Kai,Tian Guangyong
Irreversible sensorineural hearing loss is one of the most common side effects after cisplatin treatment. Prevention and reversal of hearing loss caused by cisplatin are of great importance for cancer patients, especially children. Oxidative stress is an important cause of hearing loss resulted from cisplatin, unfortunately, there is no drug yet available that can completely prevent and reverse the ototoxicity from cisplatin. Polydatin (PD) possesses excellent antioxidant and anti-inflammatory effects, however, its role in the cisplatin-induced hearing loss has not been investigated. Herein, we have explored the preventive and therapeutic effects of PD on cisplatin-induced hearing loss and the possible underlying mechanisms. In the in vivo setting with guinea pigs, we have demonstrated that PD can reduce the threshold shift of auditory brainstem response (ABR) caused by cisplatin, promote the nuclear translocation of Nuclear factor erythroid-2 related factor 2 (Nrf2), increase the expression of Nrf2 and heme oxygenase-1 (HO-1), and thus reduce the loss of outer hair cells (OHCs). PD can ameliorate cisplatin-induced hearing loss through activating the Nrf2/HO-1 signaling pathway. This study provides a potential strategy for preventing and improving hearing loss resulted from cisplatin treatment in clinics.
研究领域:
药理学
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耳鼻喉科学
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肿瘤学
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DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Feng Y,Gao S,Zhu T,Sun G,Zhang P,Huang Y,Qu S,Du X,Mou D
Context Hyperlipidemia is a highly prevalent risk factor for atherosclerosis and stroke. The currently available medications used to treat Hyperlipidemia cannot improve its oxidative stress damage. Consumption of hawthorn can regulate blood sugar and blood lipids, and its rich fruit acid is a natural antioxidant that can improve oxidative stress damage. Objective The present research aimed to investigate the protective effect of hawthorn fruit acid (HFA) on hyperlipidemia and to determine its potential molecular mechanism. Materials and methods Sprague-Dawley rats were fed a high-fat diet (HFD) to induce hyperlipidemia and treated orally with hawthorn fruit acids (HFA). Serum and liver levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD), hydrogen peroxide (CAT), and malondialdehyde (MDA) were measured. Human hepatocellular carcinoma cell lines (HepG2) cells were treated with 0.1 mM oleic acid and HFA (0.125, 0.25 mg/mL), and intracellular TC, TG, HDL-C, SOD, CAT and MDA were measured. Changes in LDLR, HMGCR, Nrf2, HO-1, NQO1 protein and gene expression were analyzed by Western blot and qPCR. Results This study found that HFA treatment effectively reduced the level of triglyceride, cholesterol, and glucose, and attenuated hepatic steatosis in rats. Additionally, oxidative stress damage of rats was effectively reduced by treatment with HFA. Western blot and qPCR analysis indicated that HFA treatment inhibited fat accumulation in HepG2 cells by upregulating LDLR and downregulating HMGCR gene expression. HFA inhibits oleic acid (OA)-induced oxidative damage to HepG2 by activating the Nrf2/HO-1 signaling pathway. Conclusion HFA administration can provide health benefits by counteracting the effects of hyperlipidemia caused by an HFD in the body, and the underlying mechanism of this event is closely related to the activation of the Nrf2/HO-1 signaling pathway.
研究领域:
药理学
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生物化学
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分子生物学
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PubMed
高影响因子
JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
·
2022
·Vol. 103
·期 2
·779-791
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IF 4.125
Huanhuan Teng,Yi Zhang,Chuanshan Jin,Tongsheng Wang,Shengzhuo Huang,Lei Li,Songzi Xie,Deling Wu,Fengqing Xu
BACKGROUND Polygonatum cyrtonema Hua is cultivated for its edible and medical value. The steam-processed rhizome of P. cyrtonema is the main form for daily consumption and it has been used traditionally in tonics for treating various age-related disorders. The aim of our study was to compare the physicochemical properties and antioxidant activity of polysaccharides respectively extracted from crude P. Cyrtonema (PCPC), and steam-processed P. cyrtonema (PCPS), and to explore a possible underlying antioxidant mechanism. RESULTS The PCPC with a molecular weight of 4.35 × 10 3 Da mainly consisted of fructose and trace amounts of glucose, whereas PCPS with 4.24 × 10 4 Da was composed of fructose, arabinose, glucose, xylose, mannose, galacturonic acid and glucuronic acid. The PCPC had a triple-helical conformation whereas PCPS was a random coil. Both exhibited free radicals- scavenging activity in vitro . In a mouse model of oxidative damage, PCPC or PCPS treatment significantly reversed histopathological alterations, reactive oxygen species (ROS) accumulation and the reduction of antioxidant enzyme activity. They both also promoted Nrf2 nuclear transport by decreasing Keap-1 expression and increasing HO-1 expression. Both in vitro and in vivo , PCPS exhibited more potent antioxidant activity than PCPC. CONCLUSION Overall, the results suggest that PCPS has a stronger effect on the prevention of oxidative damage by activating Nrf2/HO-1 antioxidant signaling. This study demonstrates the role of steam-processed P. cyrtonema rhizome and provides valuable perspective for PCPS as a functional agent. © 2022 Society of Chemical Industry.
研究领域:
药理学
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生物化学
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分子生物学
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PubMed
高影响因子
Molecular Medicine Reports
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2019
·Vol. 20
·期 2
·1017-1024
·
IF 1.851
Duzhen Zhang,Man Li
Puerarin is the major bioactive ingredient isolated from the dry root of Pueraria lobata, a plant used in traditional Chinese medicine. Puerarin has been used to treat diabetes and cataracts in China; however, its underlying mechanism of action remains unclear. The aim of the present study was to investigate the effectiveness and mechanism of puerarin in preventing cataracts in diabetic rats. Diabetes was induced by streptozocin (STZ) administration and rats were intraperitoneally injected with puerarin (25, 50 and 100 mg/kg). Blood glucose levels and cataract development were examined in the different experimental groups. In addition, the expression levels of markers associated with oxidative stress, including nuclear factor erythroid 2 like 2 (Nrf2) and heme oxygenase‑1 (HO‑1), were analyzed. The present results suggested that treatment with puerarin at 25, 50 and 100 mg/kg significantly reduced blood glucose levels and the incidence of cataract in STZ‑induced diabetic rats. Additionally, puerarin treatment reduced oxidative stress, restoring the levels of malondialdehyde and glutathione, and the activity of glutathione peroxidase. Furthermore, puerarin administration decreased the expression levels of retinal vascular endothelial growth factor and interleukin‑1β and increased the mRNA expression levels of Nrf2 and HO‑1, thus inhibiting oxidative stress. The present findings suggested that puerarin had hypoglycemic effects and that it prevented cataract development and progression in diabetic rats by reducing oxidative stress through the Nrf2/HO‑1 signaling pathway.
研究领域:
药理学
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糖尿病研究
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眼科学
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分子生物学
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2025
·
IF 4.7
Man Zheng,Fenglei Zhang,Xiang Gong,Haitao Yuan
The oxidative damage to vascular endothelial cells induced by smoking represents a significant pathogenic factor in the development of atherosclerosis. In the present study, we isolated ginseng oligopeptide extract (GOE), which emerges as a promising candidate for protecting human aortic endothelial cells (HAECs) from nicotine-induced oxidative stress. The underlying mechanisms were also explored. The GOE effectively reversed the decline in cell viability and protected HAECs from nicotine-induced oxidative damage by inhibiting the overproduction of intracellular reactive oxygen species (ROS) while preserving superoxide dismutase (SOD) activity. We identified five ginseng oligopeptides (GOPs) as the primary components of GOE. Furthermore, we demonstrated that GOE significantly alleviated nicotine-induced mitochondrial dysfunction in HAECs while promoting the nitric oxide (NO) release and the expression of GTP cyclohydrolase 1 (GTPCH1). Although the precise mechanism through which GOE mitigates nicotine-induced oxidative stress in HAECs remains to be fully elucidated, our findings indicate that GOP-1–5 serve as bioactive constituents of GOE and play a significant synergistic role in reducing nicotine-induced apoptosis and oxidative damages in HAECs. This is achieved through modulation of cellular antioxidant systems via maintaining balance within the Keap1/Nrf2/HO-1 signaling pathway. These findings suggest that GOE may function as a potential therapeutic agent against cigarette smoking-induced atherosclerosis.
研究领域:
心血管生物学
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药理学
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DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL HYPERTENSION
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2025
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IF 3.5
Hao Wang,Ke Zhou,Xiaoling Chen,Yao Tong,Qiuyan Jiang,Qiang She,Jun Xiao
Myocardial infarction (MI) is a leading cause of morbidity and mortality globally, primarily due to oxidative stress-induced cardiomyocyte apoptosis and adverse cardiac remodeling. OL-FS13, a neuroprotective peptide derived from Odorrana livida, has previously shown anti-apoptotic effects in cerebral ischemia models. However, its role in myocardial protection remains unclear. In this study, we investigated the cardioprotective effects of OL-FS13 in both in vitro and in vivo models of MI. Hydrogen peroxide (H₂O₂) was used to induce oxidative stress in primary neonatal rat cardiomyocytes, while permanent ligation of the left anterior descending (LAD) coronary artery was employed to establish a murine MI model. OL-FS13 treatment significantly attenuated cardiomyocyte apoptosis, reduced ROS accumulation, improved left ventricular function, and decreased infarct size. Mechanistically, OL-FS13 activated the Nrf2/HO-1 signaling pathway, restoring antioxidant protein levels and suppressing oxidative stress-induced apoptosis. Pharmacological inhibition of Nrf2 with ML385 abrogated the antioxidant and anti-apoptotic effects of OL-FS13 both in vitro and in vivo, confirming the central role of this pathway. These findings demonstrate that OL-FS13 exerts potent cardioprotective effects via Nrf2/HO-1 pathway activation and ROS suppression, suggesting its potential as a novel therapeutic agent for the treatment of myocardial infarction.
研究领域:
心血管病学
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分子药理学
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氧化应激生物学
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心肌缺血再灌注损伤
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信号转导
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PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2025
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IF 7.5
Yang Yu,Yurong Wang,Ziqi Yang,Zhanqiang Li,Dianxiang Lu,Xingmei Nan
Pulmonary hypertension is divided into five groups, and chronic exposure to hypoxia causes pulmonary hypertension in the third group -- high altitude pulmonary hypertension, which is commonly seen in patients with chronic obstructive pulmonary disease, sleep-disordered breathing, and interstitial lung disease. Its clinicopathological features include right heart overload and right ventricular hypertrophy, with severe patients potentially experiencing right heart failure or even death. The pathogenesis of high altitude pulmonary hypertension is complex; it includes oxidative stress, mitochondrial dysfunction, apoptosis, and pyroptosis. Pharmacological therapy may alleviate the condition if immediate descent to lower altitudes or supplemental oxygen is not possible. Herein, we preliminarily investigated the effect of methyleugenol on high altitude pulmonary hypertension through in vitro and in vivo experiments. Methyleugenol alleviated pulmonary arteriole constriction by acting on potassium ion channels, and inhibited the proliferation of pulmonary artery smooth muscle cells(PASMCs) by decreasing and reactive oxygen species levels, as well as inhibiting the expression of HIF-1α. The cardiac systolic function improved and mitochondrial structure of pulmonary artery smooth muscle cells in rats with high altitude pulmonary hypertension was significantly improved after methyleugenol gavage intervention, and malondialdehyde levels in serum of rats were decreased while those of superoxide dismutase and glutathione increased, suggesting that the reduction of oxidative stress may be one of the mechanisms to improve mitochondrial function. Western blot experiments showed that methyleugenol regulated the oxidative stress level in rats by activating Nrf2/HO-1 signaling pathway, activate p27Kip1, inhibit CDK4/CCND1/ p-ERK1/2 and inhibited HIF-1α/RASSF1/Ras axis to inhibit cell proliferation, thereby improving the occurrence and development of high altitude pulmonary hypertension in rats. The results of this study reveal that methyl eugenol has the potential to alleviate pulmonary vasoconstriction and remodeling in rat models of high-altitude pulmonary hypertension, providing a scientific basis for the application of this compound in improving pulmonary vascular remodeling.
研究领域:
药理学
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心血管病学
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分子生物学
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DOI
PubMed
高影响因子
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