Benoxaprofen inhibited the random motility and migration to the leucoattractants endotoxin-activated serum (EAS) and f-met-leu-phe of human polymorphonuclear leucocytes (PMNL) in vitro. Inhibition of random and leucoattractant-induced migration was observed at drug concentrations of greater than 1 X 10(-6) M and 1 X 10(-5) M respectively. Benoxaprofen per se was not leucotactic but was pro-oxidative in that it stimulated PMNL hexose-monophosphate shunt activity, chemiluminescence, myeloperoxidase-mediated iodination reactions and degranulation. The drug also mediated auto-oxidation of PMNL as measured by cellular auto-iodination. The relationship between benoxaprofen-mediated inhibition of PMNL migration and activation of oxidative metabolism was investigated using the anti-oxidants ascorbate and levamisole at concentrations of 10(-2) M and 10(-3) M respectively. These agents prevented the decreased motility and auto-oxidation of PMNL induced by 10(-4) M benoxaprofen. Benoxaprofen (10(-4) M) did not inhibit the migration of PMNL from 3 children with chronic granulomatous disease thus showing that intact PMNL oxidative metabolism is required for the induction of drug-mediated inhibition of cell motility. Ingestion of therapeutic doses of benoxaprofen for 7 days by normal adults gave serum drug concentrations greater than those required for detectable effects on PMNL functions in vitro (mean serum value 126 micrograms/ml). Co-incubation of normal PMNL with serum from individuals who had ingested the drug caused decreased cell migration and increased chemiluminescence. These results show that benoxaprofen inhibits PMNL migration as a consequence of pro-oxidant properties and despite its withdrawal may be the prototype of the pro-oxidative anti-inflammatory drug.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/BF01966648 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Unlocking the potential: unveiling tyrphostins with Michael-reactive cyanoacrylate motif as promising inhibitors of human 5-lipoxygenase.
Pflugers Arch
December 2024
Institute of Pharmaceutical Chemistry, Goethe University, Max-von-Laue-Str. 9, 60438, Frankfurt Am Main, Germany.
Article Synopsis
- Human 5-lipoxygenase (5-LO) is an important enzyme that helps produce substances called leukotrienes, which are involved in the immune response and can cause inflammation and cancer.
- Researchers found new chemical compounds that effectively block 5-LO, particularly focusing on a family of inhibitors called tyrphostins.
- Two specific compounds, degrasyn and AG556, were identified as strong 5-LO blockers that work by attaching to parts of the enzyme, which could lead to new treatments for inflammatory diseases and cancer.
Artificial Intelligence Large Language Models Address Anterior Cruciate Ligament Reconstruction: Superior Clarity and Completeness by Gemini Compared With ChatGPT-4 in Response to American Academy of Orthopaedic Surgeons Clinical Practice Guidelines.
Arthroscopy
September 2024
Department of Orthopaedics, The Warren Alpert Medical School of Brown University, Providence, Rhode Island, U.S.A.
Purpose: To assess the ability of ChatGPT-4 and Gemini to generate accurate and relevant responses to the 2022 American Academy of Orthopaedic Surgeons (AAOS) Clinical Practice Guidelines (CPG) for anterior cruciate ligament reconstruction (ACLR).
Methods: Responses from ChatGPT-4 and Gemini to prompts derived from all 15 AAOS guidelines were evaluated by 7 fellowship-trained orthopaedic sports medicine surgeons using a structured questionnaire assessing 5 key characteristics on a scale from 1 to 5. The prompts were categorized into 3 areas: diagnosis and preoperative management, surgical timing and technique, and rehabilitation and prevention.
Comparison of the protective effects of vanillic and rosmarinic acid on cardiac tissue: Lower limb ischemia-reperfusion model in rats.
Ulus Travma Acil Cerrahi Derg
September 2024
Department of Cardiovascular Surgery, School of Medicine, Trakya University, Edirne-Türkiye.
Background: Ischemia/reperfusion injury is one of the most challenging postoperative situations in vascular surgery, both in elective procedures with prolonged clamping time and in delayed emergency cases with vascular occlusion. The inflammatory response that develops during ischemia and the oxygen-free radicals that proliferate during reperfusion have detrimental effects on the brain, heart, and kidneys. In this study, we aimed to compare the effects of vanillic and rosmarinic acid in preventing ischemia/reperfusion injury in a lower limb ischemia-reperfusion model in rats.
View Article and Find Full Text PDFRelationship of human cytomegalovirus-infected endothelial cells and circulating leukocytes in the pathogenesis of disseminated human cytomegalovirus infection: A narrative review.
Rev Med Virol
January 2024
Microbiology and Virology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Among the leucocyte subpopulations circulating in peripheral blood of immune-compromised patients with disseminated Human cytomegalovirus (HCMV) infection, polymorphonuclear leuckocytes (PMNL) and M/M may carry infectious virus. While only in PMNL early HCMV replicative events do occur, monocytes are susceptible to complete virus replication when they enter human organs, where as macrophages become a site of active complete virus replication. In vivo leucocytes and endothelial cells interact continuously, as suggested by several in vitro experimental findings showing the bidirectional HCMV transmission from leucocytes to and from endothelial cells with the critical aid of adhesion molecules.
View Article and Find Full Text PDFAge-related exacerbation of lung damage after trauma is associated with increased expression of inflammasome components.
Front Immunol
January 2024
University Ulm, Department of Trauma, Hand, Plastic and Reconstructive Surgery, Translational and Experimental Trauma Research, Ulm, Germany.
Background: Trauma, a significant global cause of mortality and disability, often leads to fractures and hemorrhagic shock, initiating an exaggerated inflammatory response, which harms distant organs, particularly the lungs. Elderly individuals are more vulnerable to immune dysregulation post-trauma, leading to heightened organ damage, infections, and poor health outcomes. This study investigates the role of NF-κB and inflammasomes in lung damage among aged mice post-trauma.
View Article and Find Full Text PDFWant 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!