• Whole-cell Currents Recording from Ion Channels in Human Lymphocytes Treated with Anti-inflammatory Drugs in Nanoparticles Forms

      Shang, Lijun; Najafzadeh, Mojgan; Anderson, Diana (2014)
      channels that are critical for their development and function. Many ion channels contribute to T cell-mediated autoimmune and/or inflammatory responses, so they are attractive targets for pharmacological immune modulations. In this study, we conduct patch clamp experiments to exam the whole cell currents from lymphocytes after nanoparticles exposure with the aim to test if nanoparticles exposure brings any electrophysiological changes for lymphocytes, and to compare the electrophysiological responses of lymphocytes to drugs in nanoparticles forms. Our result suggests a potential inhibition of effects of IBU N on lymphocytes. Such cytotoxicity of nanoparticles in Lymphocytes may be mainly associated with the early membrane damage. These results are also mirrored by the DNA damages occurred on lymphocytes after exposure of nanoparticles. Further detailed investigation is needed to explain the changes of Lymphocytes in response to NPs in real time and dose differences. This would provide useful information in the evaluation of toxicology of nanoparticles and in understanding the underlying mechanism of their effects on ion channels in health and diseases.
    • Zinc oxide nanoparticles affect the expression of p53, Ras p21 and JNKs: an ex vivo/in vitro exposure study in respiratory disease patients

      Kumar, A.; Najafzadeh, Mojgan; Jacob, B.K.; Dhawan, A.; Anderson, Diana (2015)
      Zinc oxide (ZnO) nanoparticles are the mostly used engineered metal oxide nanoparticles in consumer products. This has increased the likelihood of human exposure to this engineered nanoparticle (ENPs) through different routes. At present, the majority of the studies concerning ZnO ENPs toxicity have been conducted using in vitro and in vivo systems. In this study, for the first time we assessed the effect of ZnO ENPs on the major cellular pathways in the lymphocytes of healthy individuals as well as in susceptible patients suffering from lung cancer, chronic obstructive pulmonary disease (COPD) and asthma. Using the differential expression analysis, we observed a significant (P < 0.05) dose-dependent (10, 20 and 40 microg/ml for 6h) increase in the expression of tumour suppressor protein p53 (40, 60 and 110%); Ras p21 (30, 52 and 80%); c-Jun N-terminal kinases; JNKs) (28, 47 and 78%) in lung cancer patient samples treated with ZnO ENPs compared to healthy controls. A similar trend was also seen in COPD patient samples where a significant (P < 0.05) dose-dependent increase in the expression of tumour suppressor protein p53 (26, 45 and 84%), Ras p21 (21, 40 and 77%), JNKs (17, 32 and 69%) was observed after 6h of ZnO ENPs treatment at the aforesaid concentrations. However, the increase in the expression profile of tested protein was not significant in the asthma patients as compared to controls. Our results reiterate the concern about the safety of ZnO ENPs in consumer products and suggest the need for a complete risk assessment of any new ENPs before its use.