Ameliorative effects of sildenafil against carbon tetrachloride induced hepatic fibrosis in rat model through downregulation of osteopontin gene expression DOI Creative Commons

Hend Elsayed Nasr,

Ahmed Medhat Hegazy,

Noha Osama El-Shaer

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 23, 2024

Abstract The liver carries out many essential tasks, such as synthesising cholesterol, controlling the body’s storage of glycogen, and detoxifying metabolites, in addition to performing, regulating homeostasis. Hepatic fibrosis is a pathological state characterized by over accumulation extracellular matrix (ECM) including collagen fibers. Sildenafil (a selective inhibitor type 5 phosphodiesterase) has anti-inflammatory, antioxidant anti-apoptotic properties. It commonly used treat erectile dysfunction male. purpose current investigation was evaluate sildenafil’s hepatoprotective potential against rats that caused carbon tetrachloride (CCl 4 ). Liver enzymes oxidative markers well profibrotic genes were determined. findings showed sildenafil alleviates hepatic dysfunctions CCl restoring normal levels ALT, AST, GGT status demonstrated increased glutathione (GSH), catalase. In addition, significantly down-regulated mRNA expressions [collagen-1α, IL-1β, osteopontin (OPN), transforming growth factor-β (TGF-β)]. Additionally, lessens periportal between lobules, congestion dilatation central vein, inflammatory cell infiltrations. As result, it hypothesized may be helpful management hepatotoxicity brought on through suppressing OPN.

Language: Английский

Carbon tetrachloride does not promote hepatic fibrosis in ob/ob mice via downregulation of lipocalin-2 protein DOI Creative Commons
Hyun Joo Shin, Kyung Eun Kim,

Hyeong Seok An

et al.

Redox Biology, Journal Year: 2025, Volume and Issue: 80, P. 103506 - 103506

Published: Jan. 18, 2025

Although leptin-deficient ob/ob mice have been investigated to determine whether hepatic steatosis promotes susceptibility hepatotoxic insults, carbon tetrachloride (CCl4)-induced fibrosis in remains largely unknown. In this study, we evaluate the pathogenic mechanisms of CCl4-treated wild-type (WT) and analyze some parameters related lipogenesis, inflammation, fibrosis, oxidative stress, apoptosis, autophagy. CCl4 treatment attenuated liver weight lipogenesis mice. Increased fibrosis-related proteins were reduced compared with WT Specifically, expression lipocalin-2 (LCN2) was markedly versus Compared mice, had neutrophil-related inflammatory genes proteins. Hepatic heme oxygenase-1 protein However, did not promote apoptosis Therefore, these findings highlight LCN2 as a key signaling factor CCl4-induced fibrosis.

Language: Английский

Citations

1
Protective efficacy of Schizandrin B on ameliorating nephrolithiasis via regulating GSK3β/Nrf2 signaling-mediated ferroptosis in vivo and in vitro DOI

Caitao Dong,

Chao Song, Ziqi He

et al.

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 117, P. 110042 - 110042

Published: March 20, 2023

Language: Английский

Citations

19
Iron as a therapeutic target in chronic liver disease DOI Creative Commons

Elias Kouroumalis,

Ioannis Tsomidis, Argyro Voumvouraki

et al.

World Journal of Gastroenterology, Journal Year: 2023, Volume and Issue: 29(4), P. 616 - 655

Published: Jan. 20, 2023

It was clearly realized more than 50 years ago that iron deposition in the liver may be a critical factor development and progression of disease. The recent clarification ferroptosis as specific form regulated hepatocyte death different from apoptosis description ferritinophagy variation autophagy prompted detailed investigations on association liver. In this review, we will present brief discussion absorption handling by with emphasis role macrophages significance regulators hepcidin, transferrin, ferritin homeostasis. regulation endogenous exogenous mod-ulators examined. Furthermore, involvement various diseases including alcoholic non-alcoholic disease, chronic hepatitis B C, fibrosis, hepatocellular carcinoma (HCC) analyzed. Finally, experimental clinical results following interventions to reduce promising manipulation presented. Most benefited inhibition using inhibitors notable exception HCC, where induction is desired effect. Current evidence mostly stems vitro vivo studies need for well-designed future trials warranted.

Language: Английский

Citations

18
Particulate Matter Induces Oxidative Stress and Ferroptosis in Human Lung Epithelial Cells DOI Creative Commons
Yujin Ahn, Yong‐Hyeon Yim, Hee Min Yoo

et al.

Toxics, Journal Year: 2024, Volume and Issue: 12(2), P. 161 - 161

Published: Feb. 19, 2024

Numerous toxicological studies have highlighted the association between urban particulate matter (PM) and increased respiratory infections lung diseases. The adverse impact on lungs is directly linked to complex composition of matter, initiating reactive oxygen species (ROS) production consequent lipid peroxidation. Excessive ROS, particularly within mitochondria, can destroy subcellular organelles through various pathways. In this study, we confirmed induction ferroptosis, an iron-dependent cell death, upon exposure PM using RT-qPCR signaling pathway analysis. We used KRISS CRM 109-02-004, certified reference material for analysis produced by Korea Research Institute Standards Science (KRISS). To validate that ferroptosis causes endothelial toxicity, assessed intracellular mitochondrial potential, ROS overproduction, peroxidation, specific biomarkers. Following PM, a significant increase in generation decrease potential were observed. Furthermore, it induced hallmarks including accumulation loss antioxidant defenses, cellular iron accumulation. addition, occurrence oxidative stress as key feature was expression levels markers such NQO1, CYP1B1, FTH1, SOD2, NRF. Finally, observed, xCT/SLC7A11, TRIM16, HMOX-1, FTL, CHAC1, GPX4. This provides evidence elevated induce stress, which ultimately triggers ferroptosis. conclusion, our results show CRM, induces production, leading subsequent These suggest may offer strategies treatment

Language: Английский

Citations

8
Anemoside B4 alleviates arthritis pain via suppressing ferroptosis‐mediated inflammation DOI Creative Commons
Chenlu Guo,

Yuan-Fen Yue,

Bojun Wang

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(4)

Published: Feb. 1, 2024

Chronic pain is the key manifestations of rheumatoid arthritis. Neuroinflammation in spinal cord drives central sensitization and chronic pain. Ferroptosis has potentially important roles occurrence neuroinflammation In current study, mouse model collagen-induced arthritis was established by intradermal injection type II collagen complete Freund's adjuvant (CFA) solution. CFA inducement resulted swollen paw ankle, mechanical spontaneous pain, impaired motor coordination. The inflammation triggered, astrocytes were activated, increased NLRP3-mediated inflammatory signal found cord. Oxidative stress ferroptosis manifested. Meanwhile, enhancive GSK-3β activity abnormal phosphorylated Drp1 observed. To investigate potential therapeutic options for arthritic mice intraperitoneally injected with AB4 three consecutive days. treatment reduced sensitivity cord, inhibited NLRP3 inflammasome-mediated response, antioxidation, decreased mitochondrial reactive oxygen species ferroptosis. Furthermore, binding through five electrovalent bonds. Our findings indicated that AB relieves inhibiting activation, increasing antioxidant capability, reducing Drp1-mediated dysfunction suppressing neuroinflammation.

Language: Английский

Citations

7
Curcumin relieves oxaliplatin‐induced neuropathic pain via reducing inflammation and activating antioxidant response DOI

Mengwei Zhang,

Xu Sun, Yiwen Xu

et al.

Cell Biology International, Journal Year: 2024, Volume and Issue: 48(6), P. 872 - 882

Published: March 13, 2024

Abstract Oxaliplatin (OXA) has shown high effectiveness in the treatment of cancers, but its anticancer clinical effects often induce neurotoxicity leading to neuropathic pain. Oxidative damage and NLRP3 inflammasome play important roles pain development. Here, mouse model was constructed by continuous intraperitoneal injection OXA. OXA administration induced mechanical pain, spontaneous thermal hyperalgesia motor disability mice. The spinal cord tissues mice exhibited suppressed antioxidative response, activated mediated inflammatory responses, increased GSK‐3β activity. Next, we injected curcumin (CUR) intraperitoneally for seven consecutive days. CUR‐treated showed thresholds, reduced number flinches, paw withdrawal latency, restored latency fall. While cord, CUR inhibited Nrf2/GPX4‐mediated antioxidant decreased mitochondrial oxidative generation. Additionally, combined with through four covalent bonds In conclusion, our findings suggest that inhibits activation, increases Nrf2 reaction, alleviates OXA‐induced

Language: Английский

Citations

6
Apolipoprotein E is required for brain iron homeostasis in mice DOI Creative Commons
Juan Ma, Qian Guo,

Meng‐Qi Shen

et al.

Redox Biology, Journal Year: 2023, Volume and Issue: 64, P. 102779 - 102779

Published: June 16, 2023

Apolipoprotein E deficiency (ApoE-/-) increases progressively iron in the liver, spleen and aortic tissues with age mice. However, it is unknown whether ApoE affects brain iron.We investigated contents, expression of transferrin receptor 1 (TfR1), ferroportin (Fpn1), regulatory proteins (IRPs), aconitase, hepcidin, Aβ42, MAP2, reactive oxygen species (ROS), cytokines glutathione peroxidase 4 (Gpx4) ApoE-/- mice.We demonstrated that induced a significant increase iron, TfR1 IRPs reduction Fpn1, aconitase hepcidin hippocampus basal ganglia. We also showed replenishment absent partly reversed iron-related phenotype mice at 24-months old. In addition, MDA, 8-isoprostane, IL-1β, IL-6, TNFα MAP2 Gpx4 hippocampus, ganglia and/or cortex old.Our findings implied required for homeostasis ApoE-/--induced due to increased IRP/TfR1-mediated cell-iron uptake as well reduced IRP/Fpn1 associated export suggested neuronal injury resulted mainly from subsequently ROS, inflammation ferroptosis.

Language: Английский

Citations

14
Ferroptosis in Liver Disease: Natural Active Compounds and Therapeutic Implications DOI Creative Commons

Zhili Wu,

Yanru Zhu,

Wen‐Chao Liu

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(3), P. 352 - 352

Published: March 15, 2024

Ferroptosis is an emerging type of regulated cell death usually accompanied by the accumulation ferrous ions (Fe2+) and lipid peroxides. As metabolic hub body, liver crucial for iron storage metabolism. The seems to be closely related ferroptosis through Liver disease greatly threatens host health, exploring effective interventions essential. Mounting studies have demonstrated that one possible pathogenic mechanisms involved in disease. Targeting may provide a promising opportunity treating However, drugs targeting are extremely limited. Therefore, it urgent need develop new safe regulators. Natural active compounds (NAC), especially those derived from traditional Chinese medicine, recently shown great therapeutic potential via modulating ferroptosis-related genes or pathways. Here, we outline molecular mechanism systematically summarize regulatory function NAC on Finally, discuss application prospects problems concerning as regulators managing

Language: Английский

Citations

5
Bioactive compound schaftoside from Clinacanthus nutans attenuates acute liver injury by inhibiting ferroptosis through activation the Nrf2/GPX4 pathway DOI
Yi Yu,

Jingwei Liang,

Zhexin Yuan

et al.

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 328, P. 118135 - 118135

Published: March 30, 2024

Language: Английский

Citations

5
A dual-response fluorescent probe to reveal the role of ferroptosis in drug-induced liver injury DOI
Jianfei Liu, Changyi Li,

Junmin Sun

et al.

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: 495, P. 153592 - 153592

Published: June 28, 2024

Language: Английский

Citations

5