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Extract from root of Pueraria lobata inhibits an acute alcohol tolerance in high-preferring (WHP) and low-preferring (WLP) alcohol-drinking rats
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Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45
showed significant disturbances in ECG recording and changes in BP. Collectively, these results suggested that ADD424042 has a clinical potential in design of novel compounds for treatment of refractory epilepsy. http://dx.doi.org/10.1016/j.pharep.2015.06.043 Toxicity of the kynurenine pathway elements to the early life stages of zebrafish (Daniorerio) Michał Majewski 1, Piotr Jakubowski 1, Piotr Podlasz 2, Natalia Kasica 2, Marta Pugaczewska 1 1
Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland 2 Department of Animal Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland Tryptophan metabolites, the substances which are intensively metabolized in animals and humans, were tested for lethality, hatching, heart-beat and teratogenicity in a 3-day assay using zebrafish embryos and for lethality in 5 day old larval forms. 3Hydroxykynurenine (3-OH-Kyn) and 3-hydroxyanthranilic acid (3-OH-AA) are known because of their neurotoxic properties through oxygen radical generation; whereas, quinolinic acid (QUIN) toxicity is a result of an NMDA receptor agonist. On the other hand, kynurenic acid (KYNA) works as a neuroprotectant and an AMPA, NMDA and kainate glutamate receptor antagonist. In the present study, zebrafish embryos and 5dpf larvae were used as a model to investigate the developmental toxicities of a nine kynurenines, namely, QUIN, kynurenic acid, kynurenine (Lkyn), 3-OH-Kyn, 3-OH-AA, anthranilic acid (AA), xanthurenic acid (XA), picolinic acid (PA) and nicotinic acid (NA). The half lethal concentration (LC50) values indicated that the rank order of toxicities of the kynurenines were QUIN > AA > KYNA > XA > 3OH-Kyn > NA > 3-OH-AA > PA. LC50 was higher in 5 dpf larvae in comparison to 24, 48 and 72 hpf embryos. The kynurenine exposure resulted in a variety of developmental lesions in the embryos/larvae, such as a delay in time to hatch or accelerated hatching, pericardial edema, malformation of head and growth retardation. These data suggest that QUIN, AA, and KYNA are more potent toxicants than others, and indicate that further research of their toxicities is required. http://dx.doi.org/10.1016/j.pharep.2015.06.044 Impact of balance between protein kinase and phosphatase activities on state-dependent memory of psychoactive drugs in passive avoidance task in mice Agnieszka Michalak, Graz˙yna Biała Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland Neuroplasticity plays a great role in memory formation as well as addiction development. Phosphorylation provokes structural and functional changes in synapses, hence mediates this specific ability of the brain to be remodeled. Psychoactive drugs may produce a very specific type of memory called state-dependent memory. It is a phenomenon in which the retrieval of newly acquired information is possible only if the subject is in the same
sensory context and physiological state as during the encoding phase. The aim of this study was to evaluate if modulation of protein kinase/phosphatase activities influences morphine- and ethanol-induced state-dependent memory, including cross statedependent memory between morphine, ethanol and nicotine. Experiments were conducted on male Swiss mice. To assess memory function passive avoidance test was used. The apparatus consists of two compartments: an illuminated one and a dark part, equipped with the energized grid floor. The test is based on the association formed between an aversive stimulus (a foot shock) and a specific environmental context. Morphine (10.0 mg/kg sc) and ethanol (1.0 g/kg ip) triggered state-dependent memory and cross state-dependent memory with an additional account of nicotine (0.1 mg/kg sc). FK-506 – a phosphatase inhibitor (1.0 and 5.0 mg/kg ip) and SL-327 – a kinase inhibitor (3.0 and 10.0 mg/kg ip) were used in order to estimate involvement of protein kinase/ phosphatase activities in cognitive effects of used psychoactive drugs. The results suggest that protein kinase/phosphatase balance is involved in morphine- and ethanol-induced state-dependent learning. http://dx.doi.org/10.1016/j.pharep.2015.06.045 Extract from root of Pueraria lobata inhibits an acute alcohol tolerance in high-preferring (WHP) and low-preferring (WLP) alcoholdrinking rats Przemysław Ł. Mikołajczak 1,2, Michał Szulc 1, Ewa Kamin´ska 1, Wanda Dyr 3, Edyta Wyszogrodzka 3, Agnieszka Gryszczyn´ska 2, Teresa Bobkiewicz-Kozłowska 1 1
Department of Pharmacology, Poznan´ University of Medical Sciences, Poznan´, Poland 2 Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, Poznan´, Poland 3 Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warszawa, Poland
The aim of this study was to examine the ability of extract from root of Pueraria lobata (kudzu) and its isoflavonoids (puerarin and daidzin) to inhibit the development of acute ethanol tolerance. The experiments were performed on male Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats treated with kudzu (500 mg/kg, po), puerarin (150 mg/kg, po) or daidzin (40 mg/kg, po) once a day for 8 consecutive days 60 min before ethanol injection. For development of alcohol tolerance the rats were injected with ethanol in a dose of 3.0 g/kg (ip) daily for 8 consecutive days and 30, 60 and 90 min after alcohol administration a hypothermia testing procedure was used. Moreover, on 8th day a sleep time period produced by ethanol was measured. It was found that WHP and WLP rats differ in their hypothermic effect of alcohol, since both on the 1st and 8th day of the experiment WLP animals showed a stronger lowering of rectal temperature. In both group of rats a tolerance to the hypothermic effect especially after 60 and 90 min was observed. Kudzu and the isoflavonoids blocked the acute alcohol tolerance especially after 90 min from administration of ethanol in WHP and WLP animals, whereas the compounds did not affect the sleep time period of rats. However, more study is needed for understanding kudzu’s mechanism involved in the development of alcohol tolerance. http://dx.doi.org/10.1016/j.pharep.2015.06.046
Abstracts – XIX Congress PTF / Pharmacological Reports 67S (2015) 2–45
showed significant disturbances in ECG recording and changes in BP. Collectively, these results suggested that ADD424042 has a clinical potential in design of novel compounds for treatment of refractory epilepsy. http://dx.doi.org/10.1016/j.pharep.2015.06.043 Toxicity of the kynurenine pathway elements to the early life stages of zebrafish (Daniorerio) Michał Majewski 1, Piotr Jakubowski 1, Piotr Podlasz 2, Natalia Kasica 2, Marta Pugaczewska 1 1
Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland 2 Department of Animal Anatomy, Faculty of Veterinary Medicine, University of Warmia and Mazury in Olsztyn, Olsztyn, Poland Tryptophan metabolites, the substances which are intensively metabolized in animals and humans, were tested for lethality, hatching, heart-beat and teratogenicity in a 3-day assay using zebrafish embryos and for lethality in 5 day old larval forms. 3Hydroxykynurenine (3-OH-Kyn) and 3-hydroxyanthranilic acid (3-OH-AA) are known because of their neurotoxic properties through oxygen radical generation; whereas, quinolinic acid (QUIN) toxicity is a result of an NMDA receptor agonist. On the other hand, kynurenic acid (KYNA) works as a neuroprotectant and an AMPA, NMDA and kainate glutamate receptor antagonist. In the present study, zebrafish embryos and 5dpf larvae were used as a model to investigate the developmental toxicities of a nine kynurenines, namely, QUIN, kynurenic acid, kynurenine (Lkyn), 3-OH-Kyn, 3-OH-AA, anthranilic acid (AA), xanthurenic acid (XA), picolinic acid (PA) and nicotinic acid (NA). The half lethal concentration (LC50) values indicated that the rank order of toxicities of the kynurenines were QUIN > AA > KYNA > XA > 3OH-Kyn > NA > 3-OH-AA > PA. LC50 was higher in 5 dpf larvae in comparison to 24, 48 and 72 hpf embryos. The kynurenine exposure resulted in a variety of developmental lesions in the embryos/larvae, such as a delay in time to hatch or accelerated hatching, pericardial edema, malformation of head and growth retardation. These data suggest that QUIN, AA, and KYNA are more potent toxicants than others, and indicate that further research of their toxicities is required. http://dx.doi.org/10.1016/j.pharep.2015.06.044 Impact of balance between protein kinase and phosphatase activities on state-dependent memory of psychoactive drugs in passive avoidance task in mice Agnieszka Michalak, Graz˙yna Biała Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Lublin, Poland Neuroplasticity plays a great role in memory formation as well as addiction development. Phosphorylation provokes structural and functional changes in synapses, hence mediates this specific ability of the brain to be remodeled. Psychoactive drugs may produce a very specific type of memory called state-dependent memory. It is a phenomenon in which the retrieval of newly acquired information is possible only if the subject is in the same
sensory context and physiological state as during the encoding phase. The aim of this study was to evaluate if modulation of protein kinase/phosphatase activities influences morphine- and ethanol-induced state-dependent memory, including cross statedependent memory between morphine, ethanol and nicotine. Experiments were conducted on male Swiss mice. To assess memory function passive avoidance test was used. The apparatus consists of two compartments: an illuminated one and a dark part, equipped with the energized grid floor. The test is based on the association formed between an aversive stimulus (a foot shock) and a specific environmental context. Morphine (10.0 mg/kg sc) and ethanol (1.0 g/kg ip) triggered state-dependent memory and cross state-dependent memory with an additional account of nicotine (0.1 mg/kg sc). FK-506 – a phosphatase inhibitor (1.0 and 5.0 mg/kg ip) and SL-327 – a kinase inhibitor (3.0 and 10.0 mg/kg ip) were used in order to estimate involvement of protein kinase/ phosphatase activities in cognitive effects of used psychoactive drugs. The results suggest that protein kinase/phosphatase balance is involved in morphine- and ethanol-induced state-dependent learning. http://dx.doi.org/10.1016/j.pharep.2015.06.045 Extract from root of Pueraria lobata inhibits an acute alcohol tolerance in high-preferring (WHP) and low-preferring (WLP) alcoholdrinking rats Przemysław Ł. Mikołajczak 1,2, Michał Szulc 1, Ewa Kamin´ska 1, Wanda Dyr 3, Edyta Wyszogrodzka 3, Agnieszka Gryszczyn´ska 2, Teresa Bobkiewicz-Kozłowska 1 1
Department of Pharmacology, Poznan´ University of Medical Sciences, Poznan´, Poland 2 Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, Poznan´, Poland 3 Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warszawa, Poland
The aim of this study was to examine the ability of extract from root of Pueraria lobata (kudzu) and its isoflavonoids (puerarin and daidzin) to inhibit the development of acute ethanol tolerance. The experiments were performed on male Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP) rats treated with kudzu (500 mg/kg, po), puerarin (150 mg/kg, po) or daidzin (40 mg/kg, po) once a day for 8 consecutive days 60 min before ethanol injection. For development of alcohol tolerance the rats were injected with ethanol in a dose of 3.0 g/kg (ip) daily for 8 consecutive days and 30, 60 and 90 min after alcohol administration a hypothermia testing procedure was used. Moreover, on 8th day a sleep time period produced by ethanol was measured. It was found that WHP and WLP rats differ in their hypothermic effect of alcohol, since both on the 1st and 8th day of the experiment WLP animals showed a stronger lowering of rectal temperature. In both group of rats a tolerance to the hypothermic effect especially after 60 and 90 min was observed. Kudzu and the isoflavonoids blocked the acute alcohol tolerance especially after 90 min from administration of ethanol in WHP and WLP animals, whereas the compounds did not affect the sleep time period of rats. However, more study is needed for understanding kudzu’s mechanism involved in the development of alcohol tolerance. http://dx.doi.org/10.1016/j.pharep.2015.06.046