Tumor necrosis factor-alpha (TNF-alpha) is recognized as a principal mediator of a variety of inflammatory conditions. Pentoxifylline (PTX), which can inhibit cellular TNF-alpha synthesis, also attenuates the toxic effect of TNF-alpha. However, the mechanism underlying PTX-induced cytoprotection is unknown. Heme oxygenase 1 (HO-1) is an enzyme which degrades heme into biliverdin, free iron, and carbon monoxide (CO). This enzyme has recently been shown to have anti-inflammatory and cytoprotective effects. In this study, we investigated whether protection by PTX against TNF-alpha-mediated toxicity could be related to its ability to induce HO-1 expression and HO activity in L929 cells. PTX in the range of 0.1-1.0mM significantly induced HO-1 expression and the resulting HO activity. Pre-incubation of L929 cells with either PTX or the HO activator hemin resulted in the protection of the cells against TNF-alpha-mediated toxicity. Zinc protoporphyrin, a specific HO competitive inhibitor, abrogated the protective effect of PTX. Hemoglobin, a scavenger of CO, reversed the protective effect of PTX. A cytoprotection comparable to PTX was observed when the cells were treated with the CO-releasing compound tricarbonyldichlororuthenium(II) dimer. These results suggest that HO-1 expression and the ensuing formation of the HO metabolite CO may be a novel pathway by which PTX protects L929 cells from TNF-alpha-mediated toxicity.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/s0006-291x(03)00123-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
An integrative lipidomics and transcriptomics study revealing Bavachin and Icariin synergistically induce idiosyncratic liver injury.
Immunopharmacol Immunotoxicol
December 2024
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Reports of traditional Chinese medicine (TCM)-related liver injury have increased over recent years; however, identifying susceptibility-related components and biomarkers remains challenging due to the heterogeneous nature of TCM and idiosyncratic drug-induced liver injury (IDILI). (PF) and (EF), commonly found in TCM prescriptions, have been implicated in IDILI, but their constituents and underlying mechanisms are poorly understood. In this study, we identified bavachin (Bav) and icariin (Ica) as susceptibility components for IDILI in PF and EF using a TNF-α-mediated mouse model.
View Article and Find Full Text PDFUnraveling cancer progression pathways and phytochemical therapeutic strategies for its management.
Front Pharmacol
August 2024
School of Pharmacy, Sharda University, Greater Noida, India.
Cancer prevention is currently envisioned as a molecular-based approach to prevent carcinogenesis in pre-cancerous stages, i.e., dysplasia and carcinoma .
View Article and Find Full Text PDFMediation analysis for TNF-α as a mediator between multiple metal exposure and kidney function.
Ecotoxicol Environ Saf
September 2024
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medicine University, Kaohsiung City 807, Taiwan; Department of Public Health and Environmental Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan; Department of Occupational and Environmental Medicine, Kaohsiung Medicine University Hospital, Kaohsiung Medicine University, Kaohsiung 807, Taiwan; Ph.D. Program in Environmental and Occupational Medicine, College of Medicine, and Research Center for Precision Environmental Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan. Electronic address:
The association between metal mixtures and kidney function has been reported. However, reports on the mechanism of metal toxicity were limited. Oxidative stress was reported as a possible cause.
View Article and Find Full Text PDFThe marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol prevents TNF-α-mediated impairment of mineralization in mouse osteoblastic MC3T3-E1 cells: Impact of macrophage activation.
Chem Biol Interact
February 2024
Watanabe Oyster Laboratory Co. Ltd., 490-3, Shimoongata-cho, Hachioji, 192-0154, Tokyo, Japan; Graduate School of Science and Engineering, Soka University, 1-236, Tangi-machi, Hachioji, Tokyo, 192-8577, Japan; Faculty of Health Sciences, Hokkaido University, Sapporo, 060-0812, Japan.
The phenolic antioxidant 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), found in the Pacific oyster Crassostrea gigas, is a superior peroxyl radical scavenger compared to other materials, including Trolox. DHMBA may play an important role in the prevention of health disorders. This study elucidates whether DHMBA prevents the impairment of mineralization of mouse osteoblastic MC3T3-E1 cells under inflammatory conditions by using mouse macrophage RAW264.
View Article and Find Full Text PDFA new insight into fluoride induces cardiotoxicity in chickens: Involving the regulation of PERK/IRE1/ATF6 pathway and heat shock proteins.
Toxicology
January 2024
College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China. Electronic address:
Article Synopsis
- Fluorosis, caused by fluoride exposure, is a major health risk for both humans and animals, particularly affecting heart health and necessitating further research into its mechanisms.
- A study on chickens revealed that increasing sodium fluoride doses (0, 500, 1000, and 2000 mg/kg) led to significant heart damage, including congested tissue and disrupted myofiber structures.
- The research found that sodium fluoride activated stress response and inflammatory pathways, causing both apoptosis and necroptosis, which contributed to cardiac injury, highlighting the importance of understanding fluoride's cardiotoxic effects.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!