scholarly journals Electroacupuncture Enhances Antioxidative Signal Pathway and Attenuates Neuropathic Pain Induced by Chemotherapeutic Paclitaxel

2019 ◽  
pp. 501-510 ◽  
Author(s):  
X. ZHAO ◽  
L. LIU ◽  
Y. WANG ◽  
G. WANG ◽  
Y. ZHAO ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Dorsal Root ◽  
Thermal Sensitivity ◽  
Antioxidant Response ◽  
Signal Pathway ◽  
Superoxide Dismutases ◽  
Behavioral Test ◽  
Thermal Hypersensitivity

One of the significant limiting complications of paclitaxel is painful peripheral neuropathy during its therapy for several types of cancers. Our recent study showed that impairment of Nrf2-antioxidant response element (Nrf2-ARE) and upregulation of oxidative signals in the dorsal root ganglion (DRG) of rats with treatment of paclitaxel result in neuropathic pain. The purpose of this study was to examine the beneficial role played by electroacupuncture (EA) in modifying neuropathic pain evoked by paclitaxel via Nrf2-ARE and oxidative mechanisms. Behavioral test was performed to determine mechanical and thermal sensitivity in rats. Western Blot analysis and ELISA were used to examine expression of Nrf2-ARE and superoxide dismutases (SOD); and the levels of products of oxidative stress in the DRG. Our data showed that paclitaxel increased mechanical and thermal sensitivity and this was accompanied with impaired Nrf2-ARE and SOD in the DRG and amplified products of oxidative stress (i.e. 8-isoprostaglandin F2α and 8-hydroxy-2’-deoxyguanosine). EA treatment largely restored the levels of Nrf2-ARE/SOD and inhibited products of oxidative stress and thereby attenuated mechanical and thermal hypersensitivity induced by paclitaxel. In conclusion, we revealed specific signaling pathways leading to paclitaxel-evoked neuropathic pain, including impairment of Nrf2-ARE and heightened oxidative signals. We further provided evidence for the role of EA in alleviating paclitaxel-neuropathic pain via these molecular mediators.

scholarly journals Nociceptive Behavior Induced by Chemotherapeutic Paclitaxel and Beneficial Role of Antioxidative Pathways

2018 ◽  
pp. 491-500 ◽  
Author(s):  
H. MIAO ◽  
J. XU ◽  
D. XU ◽  
X. MA ◽  
X. ZHAO ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Nadph Oxidase ◽  
Thermal Sensitivity ◽  
Antioxidant Response ◽  
Inhibitory Effect ◽  
Oxidase Inhibitor ◽  
Antioxidant Vitamin ◽  
Beneficial Effects ◽  
Thermal Hypersensitivity

Paclitaxel is used for the treatment of several types of cancers. However, one of the significant limiting complications of paclitaxel is painful peripheral neuropathy during its therapy. In this study we examined the engagement of antioxidative signal pathway of the dorsal root ganglion (DRG) in mechanical and thermal hypersensitivity evoked by paclitaxel. Behavioral test was performed to determine mechanical and thermal sensitivity in rats. Western blot analysis and ELISA were used to examine expression of Nrf2-antioxidant response element (ARE) and superoxide dismutases (SOD); and the levels of products of oxidative stress in the DRG. Our results show that paclitaxel increased mechanical and thermal sensitivity as compared with vehicle control animals. Paclitaxel also impaired Nrf2-ARE and SOD in the DRG and amplified products of oxidative stress, namely 8-isoprostaglandin F2α and 8-hydroxy-2’-deoxyguanosine. Systemic administration of SOD mimetic using tempol, antioxidant vitamin C or blocking oxidative pathway using NADPH oxidase inhibitor (GKT137831) attenuated mechanical and thermal hypersensitivity induced by paclitaxel. This inhibitory effect was accompanied with decreases of proinflammatory cytokines (PICs) such as IL-1β, IL-6 and TNF-α in the DRG. In conclusion, the data revealed impairment of Nrf2-ARE and heightened oxidative and PIC signals in the DRG of paclitaxel rats, leading to neuropathic pain. Balancing of reactive oxygen species by supplying antioxidants and/or inhibiting NADPH oxidase appears significant to yield beneficial effects in neuropathic pain conditions after chemotherapeutic paclitaxel.

scholarly journals The Protective Effect of Bergamot Polyphenolic Fraction (BPF) on Chemotherapy-Induced Neuropathic Pain

2021 ◽  
Vol 14 (10) ◽  
pp. 975
Author(s):  
Sara Ilari ◽  
Filomena Lauro ◽  
Luigino Antonio Giancotti ◽  
Valentina Malafoglia ◽  
Concetta Dagostino ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Glutamate Transporter ◽  
Thermal Hyperalgesia ◽  
Chemotherapeutic Agents ◽  
Preventive Strategy ◽  
Polyphenolic Extract ◽  
Thermal Hypersensitivity

Paclitaxel is a chemotherapeutic drug used for cancer treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is a common major dose-limiting side effect of many chemotherapeutic agents, including paclitaxel. CIPN is accompanied by mechanical and thermal hypersensitivity that resolves within weeks, months, or years after drug termination. To date, there is no available preventive strategy or effective treatment for CIPN due to the fact that its etiology has not been fully explained. It is clear that free radicals are implicated in many neurodegenerative diseases and recent studies have shown the important role of oxidative stress in development of CIPN. Here, we observed how, in rats, the administration of a natural antioxidant such as the bergamot polyphenolic extract (BPF), can play a crucial role in reducing CIPN. Paclitaxel administration induced mechanical allodynia and thermal hyperalgesia, which began to manifest on day seven, and reached its lowest levels on day fifteen. Paclitaxel-induced neuropathic pain was associated with nitration of proteins in the spinal cord including MnSOD, glutamine synthetase, and glutamate transporter GLT-1. This study showed that the use of BPF, probably by inhibiting the nitration of crucial proteins involved in oxidative stress, improved paclitaxel-induced pain behaviors relieving mechanical allodynia, thermal hyperalgesia, thus preventing the development of chemotherapy-induced neuropathic pain.

Role of TRPV4-P2X7 Pathway in Neuropathic Pain in Rats with Chronic Compression of the Dorsal Root Ganglion

2021 ◽  
Author(s):  
Xiaohua Fan ◽  
Chuanwei Wang ◽  
Junting Han ◽  
Xinli Ding ◽  
Shaocan Tang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Dorsal Root

Role of Exercise Activity in Alleviating Neuropathic Pain in Diabetes via Inhibition of the Pro-Inflammatory Signal Pathway

2018 ◽  
Vol 21 (1) ◽  
pp. 14-21 ◽  
Author(s):  
Xiao-Qiu Ma ◽  
Jing Qin ◽  
Hong-Yan Li ◽  
Xiu-Li Yan ◽  
Yong Zhao ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Tumor Necrosis ◽  
Signal Pathway ◽  
Sensory Nerves ◽  
Glucose Levels ◽  
Tnf Α ◽  
Exercise Activity ◽  
Necrosis Factor ◽  
Pro Inflammatory Cytokines

Hyperalgesia and allodynia are commonly observed in patients with diabetic neuropathy. The treatment and management of painful peripheral neuropathy is important in these patients. The purpose of this study was to examine the role of exercise in modulating neuropathic pain induced by diabetes. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (STZ). Control rats received saline injections. Groups included control rats without exercise (NT-control, n = 12), control rats with exercise (EX-control, n = 16), STZ rats without exercise (NT-STZ, n = 18), and STZ rats with exercise (EX-STZ, n = 22). Rats in EX groups ran on a treadmill 4 days/week for 5 weeks beginning from the week of STZ administration. Mechanical hypersensitivity (mechanical paw withdrawal thresholds [PWTs]) and glucose levels were tested weekly. Then, enzyme-linked immunoassay and Western blot analysis were used to determine the levels of pro-inflammatory cytokines (PICs) and their receptors in sensory nerves. PWTs were significantly increased after 4–5 weeks of exercise in STZ rats ( p < .05 vs. NT-STZ rats). Inhibition of neuropathic pain by exercise in STZ rats was accompanied by decreases in interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α levels and downregulated expression of their receptors. Furthermore, blocking individual PIC receptors elevated PWTs to a greater degree in STZ rats ( p < .05 vs. control rats). Overall, our data suggest that exercise can play a role in improving neuropathic pain induced by STZ and that PIC signaling is a part of the mechanism involved in this effect.

scholarly journals Redox Signaling in Diabetic Nephropathy: Hypertrophy versus Death Choices in Mesangial Cells and Podocytes

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Gina Manda ◽  
Alexandru-Ionel Checherita ◽  
Maria Victoria Comanescu ◽  
Mihail Eugen Hinescu
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
Mesangial Cells ◽  
Antioxidant Response ◽  
Molecular Networks ◽  
Integrative Approach ◽  
Renal Cells ◽  
Diagnosis And Prognosis ◽  
New Therapeutic Approaches

This review emphasizes the role of oxidative stress in diabetic nephropathy, acting as trigger, modulator, and linker within the complex network of pathologic events. It highlights key molecular pathways and new hypothesis in diabetic nephropathy, related to the interferences of metabolic, oxidative, and inflammatory stresses. Main topics this review is addressing are biomarkers of oxidative stress in diabetic nephropathy, the sources of reactive oxygen species (mitochondria, NADPH-oxidases, hyperglycemia, and inflammation), and the redox-sensitive signaling networks (protein kinases, transcription factors, and epigenetic regulators). Molecular switches deciding on the renal cells fate in diabetic nephropathy are presented, such as hypertrophyversusdeath choices in mesangial cells and podocytes. Finally, the antioxidant response of renal cells in diabetic nephropathy is tackled, with emphasis on targeted therapy. An integrative approach is needed for identifying key molecular networks which control cellular responses triggered by the array of stressors in diabetic nephropathy. This will foster the discovery of reliable biomarkers for early diagnosis and prognosis, and will guide the discovery of new therapeutic approaches for personalized medicine in diabetic nephropathy.

scholarly journals Lycopene Treatment Ameliorates Amyloid Plaque Deposition and Memory Impairment in the APP/PS1 Mice

2021 ◽  
Author(s):  
Shanshan Ou ◽  
Yinchao Fang ◽  
Tong Wu ◽  
Jie Xu ◽  
Kaihua Guo
Keyword(s):  
Oxidative Stress ◽  
Oxidative Damage ◽  
Western Blot ◽  
Chronic Inflammation ◽  
Signal Pathway ◽  
Qualitative Assessment ◽  
Cell Cytotoxicity ◽  
Rt Pcr

Abstract Alzheimer’s disease (AD) is a neurodegenerative condition associated with oxidative stress and neuroinflammation. Lycopene has previously been shown to ameliorate neuroinflammation and exert protection against oxidative damage in neuroblastoma cells. The role of this compound in reversing cognitive dysfunction in AD has yet to be determined. The present study investigates the role of lycopene in AD with an in vitro Aβ1-42-induced cell cytotoxicity model as well as the in vivo APP/PS1 mouse model. The activation of Nrf2 signal pathway was assessed using western blot and RT-PCR. MDA, 8-OHdG, ROS, SOD, GHS and GSSG measurements were carried out using the specialized assay kits. The Morris water maze was used to examine qualitative assessment of memory and spatial learning. Immunofluorescence was used to visualize astrocytes and microglia activation as well as brain β-amyloid (Aβ) deposition. The NeuN positive cells were detected by immunofluorescence and western blot. Levels of cerebral cytokines were quantified using RT-PCR. Lycopene ameliorates oxidative damage in the Aβ1-42-triggered cell cytotoxicity model via Nrf2-ARE signal pathway activation, which is regulated by AKT-GSK3β pathway. In addition, lycopene improves the cognitive impairment and reduces the Aβ deposition. Mechanistically, lycopene attenuates neuron loss, decreases chronic inflammation and activates cerebral Nrf2-ARE signaling pathway in APP/PS1 mice. The results suggest that lycopene alleviates oxidative stress via AKT- Nrf2-ARE pathway. And early administration of lycopene improves cognitive deficits by reducing Aβ deposition, neuronal loss and decreasing the degree of chronic inflammation.

scholarly journals The copper chaperone CcsA coupling with superoxide dismutase SodA mediates oxidative stress response in Aspergillus fumigatus

2021 ◽  
Author(s):  
Wenlong Du ◽  
Pengfei Zhai ◽  
Shuai Liu ◽  
Yuanwei Zhang ◽  
Ling Lu
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Stress Response ◽  
Aspergillus Fumigatus ◽  
Fungal Pathogens ◽  
Oxidative Stress Response ◽  
Superoxide Dismutases ◽  
Oxygen Species ◽  
Oxidative Response

Superoxide dismutases (SODs) are important metalloenzymes that protect fungal pathogens against the toxic effects of reactive oxygen species (ROS) generated by host defense mechanisms during the infection process. The activation of Cu/Zn-SOD1 is found to be dependent on its c haperone Ccs1 ( c opper c haperone for S OD1). However, the role of Ccs1 ortholog in the human pathogen Aspergillus fumigatus and how these SODs coordinate to mediate oxidative stress response remain elusive. Here, we demonstrated that A. fumigatus CcsA, a Saccharomyces cerevisiae Ccs1 ortholog, is required for cells in response to oxidative response and the activation of Sod1. Deletion of ccsA resulted in increased ROS accumulation and enhanced sensitivity to oxidative stress due to loss of SodA activity. Molecular characterization of CcsA revealed that the conserved CXC motif is required not only for the physical interaction with SodA but also for the oxidative stress adaption. Notably, addition of Mn 2+ or overexpression of cytoplasmic Mn-SodC could rescue the defects of the ccsA or sodA deletion mutant, indicating the important role of Mn 2+ and Mn-SodC in ROS detoxification; however, deletion of CcsA-SodA complex could not affect A. fumigatus virulence. Collectively, our findings demonstrate that CcsA functions as a Cu/Zn-Sod1 chaperone that participates in the adaptation to oxidative stress in A. fumigatus and provide a better understanding of the CcsA-SodA complex-mediated oxidative stress response in filamentous fungi. IMPORTANCE Reactive oxygen species (ROS) produced by phagocytes have been reported to participate in the killing of fungal pathogens. Superoxide dismutases (SODs) are considered to be the first defense line against superoxide anions. Characterizing the regulatory mechanisms of SOD activation is important for understanding how fungi adapt to oxidative stress in hosts. Our findings demonstrated that CcsA functions as a SodA chaperone in A. fumigatus and that the conserved CXC motif within CcsA is required for its interaction with SodA and the CcsA-SodA-mediated oxidative response. These data may provide new insights into how fungal pathogens adapt to oxidative stress via the CcsA-SodA complex.

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