Inhibitory effect of cisplatin and [Pt(dach)Cl2] on the activity of phospholipase A2

This work has been focused on testing the influence of two selected Pt(II) complexes cisplatin, Pt(NH3)2Cl2, and [Pt(dach)Cl2] on the activity of porcine pancreatic phospholipase A2 (PLA2). It has been assumed that this enzyme plays a role in carcinogenesis and that it could be a target in the tumour therapy. The results of this study show that both Pt(II) complexes inhibit the activity of the enzyme, though they bind to it in a different manner. While cisplatin interacts with the enzyme in an acompetitive manner, the stable interaction of [Pt(dach)Cl2] with PLA2 could not be detected under our experimental conditions. © 2013 Informa UK, Ltd

Lipid status of A2780 ovarian cancer cells after treatment with ruthenium complex modified with carbon dot nanocarriers: a multimodal SR-FTIR spectroscopy and MALDI TOF Mass Spectrometry Study MALDI TOF Mass Spectrometry Study

In the last decade, targeting membrane lipids in cancer cells has been a promising approach that deserves attention in the field of anticancer drug development. To get a comprehensive understanding of the effect of the drug [Ru(¿5-Cp)(PPh3)2CN] (RuCN) on cell lipidic components, we combine complementary analytical approaches, matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI TOF MS) and synchrotron radiation-based Fourier transform infrared (SR-FTIR) spectroscopy. Techniques are used for screening the effect of potential metallodrug, RuCN, without and with drug carriers (carbon dots (CDs) and nitrogen-doped carbon dots (N-CDs)) on the lipids of the human ovarian cancer cell line A2780. MALDI TOF MS results revealed that the lysis of ovarian cancer membrane lipids is promoted by RuCN and not by drug carriers (CDs and N-CDs). Furthermore, SR-FTIR results strongly suggested that the phospholipids of cancer cells undergo oxidative stress after the treatment with RuCN that was accompanied by the disordering of the fatty acid chains. On the other hand, using (N-)CDs as RuCN nanocarriers prevented the oxidative stress caused by RuCN but did not prevent the disordering of the fatty acid chain packing. Finally, we demonstrated that RuCN and RuCN/(N-)CDs alter the hydration of the membrane surface in the membrane—water interface region.ALBA Synchrotron, MIRAS Beamline (experiment No. 2019093770). This work was also supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (grant 451-03-68/2020-14/200017); FCT(CQM Base Fund—UIDB/00674/2020, Programmatic Fund—UIDP/00674/2020); Madeira 14-20 Program (project Reforço do Investimentoem Equipamentos e Infrastructures Científcasna RAM (PROEQUIPRAM) M1420-01-0145-FEDER-000008); and Agência Regional para o Desenvolvimento da Investigação, Tecnologia e Inovação (ARDITI) through the ARDITI-CQM/2018/007-PDG (Fellowship Grant to M.G.), project M1420-01-0145-FEDER-000005-CQM+ (Madeira 14—20)

Experimental design for optimizing MALDI-TOF-MS analysis of palladium complexes

This paper presents optimization of matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometer (MS) instrumental parameters for the analysis of chloro(2,2 , 2 -terpyridine) palladium(II) chloride dihydrate complex applying design of experiments methodology (DoE). This complex is of interest for potential use in the cancer therapy. DoE methodology was proved to succeed in optimization of many complex analytical problems. However, it has been poorly used for MALDI-TOF-MS optimization up to now. The theoretical mathematical relationships which explain the influence of important experimental factors (laser energy, grid voltage and number of laser shots) on the selected responses (signal to noise - S/N ratio and the resolution - R of the leading peak) is established. The optimal instrumental settings providing maximal S/N and R are identified and experimentally verified

Comparison of blood pro/antioxidant levels before and afer acute exercise in athletes and non-athletes

The aims of our study were to assess the redox state of adolescent athletes and non-athletes both at rest and afer acute exposure to physical load and to find relations between parametersof redox state and morphofunctional characteristics of subjects. 58 young handball players and 37 non-athletes were subjected to body composition analysis, measuring of maximal oxygen consumption and blood sampling immediately before and afer a maximal progressive exercise test. At rest, athletes had significantly higher superoxide dismutase (SOD) and catalase (CAT) activity, higher levels of reduced glutathione (GSH) and nitric oxide (NO) and lower levels of lipid peroxidation (TBARS) compared with non-athletes. A maximal exercise test induced statistically significant rise of superoxide anion radical (O 2-), hydrogen peroxide (H 2O 2) and NO levels in non-athletes, while TBARS levels decreased. Athletes experienced the fall in NO levels and the fall in CAT activity. Afer exercise, athletes had significantly lower levels of O 2- compared with non-athletes. Two way repeated measures ANOVA showed that the response of O 2-, NO and TBARS to the exercise test was dependent on the sports engagement (training experience) of subjects. Significant correlations between morphofunctional and redox parameters were found. These results suggest that physical fitness affects redox homeostasis

Immunomodulatory actions of central ghrelin in diet-induced energy imbalance

We investigated the effects of centrally administered orexigenic hormone ghrelin on energy imbalance-induced inflammation. Rats were subjected for four weeks to three different dietary regimes: normal (standard food), high-fat (standard food with 30% lard) or food-restricted (70%, 50%, 40% and 40% of the expected food intake in 1st, 2nd, 3rd and 4th week, respectively). Compared to normal-weight controls, starved, but not obese rats had significantly higher levels of proinflammatory cytokines (TNF, IL-1 beta, IFN-gamma) in the blood. When compared to normally fed animals, the hearts of starved and obese animals expressed higher levels of mRNAs encoding proinflammatory mediators (TNF, IL-1 beta, IL-6, IFN-gamma, IL-17, IL-12, iNOS), while mRNA levels of the anti-inflammatory TGF-beta remained unchanged. Intracerebroventricular (ICV) injection of ghrelin (1 mu g/day) for five consecutive days significantly reduced TNF, IL-1 beta and IFN-gamma levels in the blood of starved rats, as well as TNF, IL-17 and IL-12p40 mRNA expression in the hearts of obese rats. Conversely, ICV ghrelin increased the levels of 1FN-gamma, IL-17,1L-12p35 and IL-12p40 mRNA in the heart tissue of food-restricted animals. This was associated with an increase of immunosuppressive ACTH/corticosterone production in starved animals and a decrease of the immunostimulatory adipokine leptin both in food-restricted and high-fat groups. Ghrelin activated the energy sensor AMP-activated protein kinase (AMPK) in the hypothalamus and inhibited extracellular signal-regulated kinase (ERK) in the hearts of obese, but not starved rats. Therefore, central ghrelin may play a complex role in energy imbalance-induced inflammation by modulating HPA axis, leptin and AMPK/ERK signaling pathways. (C) 2011 Elsevier Inc. All rights reserved