In vitro antiproliferative effects of Fe3O4_BA loaded

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... I. Trivi˜no1. 1 ISP, Análisis de Ilícitos, Santiago, Chile. 2 ISP, Biotecnología, Santiago, Chile. Cocaine hydrochloride is a highly addictive illicit drug, which gen-.

Abstracts / Toxicology Letters 295S (2018) S69–S266

P06-24 Toxicological evaluation of the interaction between circadian rhythm activators and general anesthetics A. Aydin ∗ , F. Kelleci, M. Hamitoglu Yeditepe University Faculty of Pharmacy, Toxicology, Istanbul, Turkey The circadian rhythm lasts about 24 hours and is constituted by 4 main genes/proteins; Circadian Locomotor Output Cycle Clock (Clock), Brain-Muscle-Arnt-Like protein-1 (Bmal1), Cryptochrome (Cry) and Period (Per). Many pathologies, diseases, and medications including general anesthetic agents are thought to cause a change in these genes/proteins. On the other hand the activation or inhibition of the genes/proteins can contribute to the reduction of the oxidative stress potential of anesthetic agents. We investigated the effect of combination therapy of KL001 with isoflurane. Twentyfour mice were randomly divided into 4 groups of 6 animals each as a control, KL001, isoflurane and KL001 plus isoflurane group. Animals were exposed to isoflurane for 4 hours and KL001 was administered of 100 mg/kg at night hours. The Cry levels and oxidative stress parameters including malondialdehyde (MDA) level and superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) activities were investigated in liver, kidney, brain, and erythrocyte. Our results showed decreased MDA level in erythrocyte and liver, increased GSH-Px activity in liver and brain, increased SOD activity in erythrocyte, kidney, and brain, decreased CAT activity in liver in isoflurane group. According to our findings, isoflurane changed the oxidative stress parameters remarkably in brain. We also found a decrease of Cry level in the plasma, liver, and brain in isoflurane group. KL001 increased Cry level inhibited by isoflurane and decreased the isoflurane-induced oxidative stress. In conclusion, our data indicated that we can reduce the potential oxidative stress of isoflurane or other anesthetic agents by triggering the Cry level with a synthetic activator or by arranging drug administration time at certain period of the day. Especially in early hours of the morning, KL001 may be protective against isoflurane-induced oxidative stress. In further research, the effects of Per, Clock, and Bmal1 on anesthetic agents toxicity can also be investigated. It can be determined at which time the operations are performed to create the least toxicity. https://doi.org/10.1016/j.toxlet.2018.06.644 P06-25 This poster abstract has been withdrawn https://doi.org/10.1016/j.toxlet.2018.06.1361 P06-26 In vitro antiproliferative effects of Fe3 O4 BA loaded liposomes C.G. Farcas 1,2,∗ , E.A. Moaca 2 , D. Coricovac 2 , C. Dehelean 2 , F. Loghin 1 1 “Iuliu Hatieganu” University of Medicine and Pharmacy, Toxicology, Cluj-Napoca, Romania 2 “Victor Babes” University of Medicine and Pharmacy, Toxicology, Timisoara, Romania

Betulinic acid (BA) is a phytocompound which has been reported to exhibit multiple pharmacological activities, such as: antitumoral effect with selectivity on tumor cells, anti-inflammatory, antioxidant, antimalarial and antimicrobial properties. However, BA is a

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highly hydrophobic compound. This property limits its bioavailability and makes it imposible for in vivo administration. The present study proposes a new formulation of BA as Fe3 O4 BA loaded liposomes, which might improve its membrane permeability. Fe3 O4 nanoparticles serve as carriers and as a method to augment BA efficacy by making the liposomes suitable for hyperthermia therapy. The liposomes containing magnetic nanoparticles (Fe3 O4 ) and BA were synthetized by thin film dispersing method and characterized by standard methods, such as: FTIR, DSC, zeta potential, TEM (transmission electron microscopy) in terms of active compound content, size and stability. The cytotoxic effects of the novel liposomes was evaluated on human healthy and breast cancer cell lines (MCF7, MDA-MB-231) by MTT and LDH assays. The Fe3 O4 BA loaded liposomes obtained were stable and with the sizes in the range recommended for biological use. Moreover, these liposomes exhibited a higher antitumor activity when compared with BA liposomes and BA in dimethylsulfoxide, what indicates a synergistic effect of BA and Fe3 O4 formulated as liposomes. These data will be used as background for further in vivo studies to demonstrate their efficacy as antitumor agents in breast cancer animal models. Acknowledgements: This research was supported by a grant of “Iuliu Hatieganu” University of Medicine and Pharmacy, project number 1300/23/13.01.2017. https://doi.org/10.1016/j.toxlet.2018.06.646 P06-27 Evaluation of the cytotoxicity of cocaine and adulterants in precursor cells of the glia R.A. Rocha 1,∗ , J. Figueroa 1 , R. Manzo 2 , D. Diaz 2 , A. Vasquez 2 , ˜ 1 D. Soto 2 , B. Duffau 1 , I. Trivino 1 2

ISP, Análisis de Ilícitos, Santiago, Chile ISP, Biotecnología, Santiago, Chile

Cocaine hydrochloride is a highly addictive illicit drug, which generates harmful effects on the health of population, specifically in the nervous system. A high percentage of the cocaine consumed in our country is adulterated with substances such as caffeine or levamisole. In relation to these adulterants substance it is unknown if such substances are less or more harmful than cocaine itself. The objective of this study has been to evaluate the cytotoxicity of cocaine and adulterants using the line human fetal glial cells from brain SVG-P12, through the use of viability, apoptosis and cell necrosis assays. The results show that the exposure to cocaine for 24 hours (≥ 5 mM) generates a decrease in cell viability and an increase in apoptosis and cell necrosis (≥ 0.5 mM). With respect to tested adulterants, a decrease in cell viability was observed due to the exposure of caffeine (≥ 15 mM) and levamisole (≥ 7.5 mM);observing that adulterants produce a decrease in cell viability at higher concentrations than cocaine. In the same way as for cocaine, an increase in apoptosis and cell necrosis was observed (dose-dependent) for caffeine and levamisole (≥ 2 mM). From this study it can be concluded that the harmful effects of cocaine in precursor cells of the glia occur at lower concentrations, than levamizol and caffeine, and that it is of interest to evaluate the effects of the mixtures of these drugs. https://doi.org/10.1016/j.toxlet.2018.06.647

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