No / Lymphocytes have many ion channels. These ion channels contribute to T cell-mediated autoimmune and/or inflammatory responses and therefore are targets for pharmacological immune modulation [1]. Lymphocytes are also suitable surrogate cells for cancer [2] and other diseases states [3] where inflammation is associated with increasing disease incidence. Non-steroidal anti-inflammatory drugs (NSAIDs), such as aspirin, have been associated with anti-tumour effects in cancers [4]. We recently compared DNA damage caused by the nanoparticle forms (NPs) of the NSAIDs, aspirin and ibuprofen and their bulk forms in peripheral blood lymphocytes of patients with respiratory diseases and healthy individuals in the Comet and micronucleus assays [5]. In this present study, we investigate electrophysiological changes from lymphocytes after NP exposure and compare these results with their DNA damage. 10 ml peripheral blood was collected from patients and healthy control individuals. Ethical permission was obtained from the Bradford Ethics Committee REC ref no: 09/H1313/37, ReDA no: 1202, and the University of Bradford ref no: 0405/8. Ibuprofen USP was purchased from Albermarle Europe sprl (Belgium). Pharmcoat 606 (HPMC) was kindly donated by Shinetsu (Japan). Aspirin and sodium lauryl sulphate were purchased from Sigma. Kollidon 30 (PVP K-30) was purchased from BASF (UK). Bulk and nano compound suspensions of aspirin and ibuprofen (IBU) were kindly prepared by Lena Nanoceutics (Bradford, UK). Whole blood collected from healthy individuals and cancer patients were treated for 30 mins with 500µg/ml of IBU bulk and nano forms separately. Whole-cell currents were recorded with normal patch clamping technique. The extracellular solution contained (in mM) the following: NaCl 125; KCl 5; MgCl2 1; CaCl2 2.5; HEPES 10; pH 7.4. The electrode internal solution contained (in mM) the following: KF 120; MgCl2 2; HEPES 10; EGTA 10; and CaCl2 1, pH 7.4. All experiments were carried out at room temperature. Compared with untreated cells, lymphocytes treated with IBU in NP form had lower whole-cell currents and the activities of ion channels were inhibited by 20% compared to those in bulk form. This result is mirrored by the DNA damage which occurred in lymphocytes after exposure to nanoparticles [5]. Although the intracellular biochemical mechanisms and ion channels involved in our nanoparticle toxicity remain to be determined, this study provides direct evidence that 500 μg/ml IBU in nano form can cause membrane damage to lymphocytes after a relatively short exposure. Such cytotoxicity of nanoparticles in lymphocytes may be associated with early membrane damage. Further detailed investigation is needed to explain the changes of lymphocytes in response to different concentrations of NPs in real time. / Poster communications
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/10487 |
| Date | January 2014 |
| Creators | Shang, Lijun, Najafzadeh, Mojgan, Anderson, Diana |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Other, No full-text in the repository |
Page generated in 0.0026 seconds