Primerjava toksičnosti etanola in acetaldehida za podganje astrocite v primarni kulturi

This study compared the effects of toxicity of ethanol and its first metabolite acetaldehyde in rat astrocytes through cell viability and cell proliferation. The cells were treated with different concentrations of ethanol in the presence or absence of a catalase inhibitor 2-amino-1,2,4 triazole (AMT) or with different concentrations of acetaldehyde. Cell viability was assessed using the trypan blue test. Cell proliferation was assessed after 24 hours and after seven days of exposure to either ethanol or acetaldehyde. We showed that both ethanol and acetaldehyde decreased cell viability in a dose-dependent manner. In proliferation studies, after seven days of exposure to either ethanol or acetaldehyde, we observed a significant dose-dependent decrease in cell number. The protein content study showed biphasic dose-response curves, after 24 hours and seven days of exposure to either ethanol or acetaldehyde. Co-incubation in the presence of AMT significantly reduced the inhibitory effect of ethanol on cell proliferation. We concluded that long-term exposure of astrocytes to ethanol is more toxic than acute exposure. Acetaldehyde is a much more potent toxin than ethanol, and at least a part of ethanol toxicity is due to ethanol’s first metabolite acetaldehyde.V študiji smo primerjali toksičnost etanola in njegovega prvega metabolita acetaldehida za podganje astrocite z določitvijo celične viabilnosti in proliferacije. Celične kulture smo tretirali z različnimi koncentracijami etanola, etanola v prisotnosti inhibitorja katalaze 2-amino-1,2,4 triazol-a (AMT) ali z različnimi koncentracijami acetaldehida. Celično viabilnost smo vrednotili s pomočjo testa s tripanskim modrilom, celično proliferacijo pa s štetjem celic in določitvijo koncentracije proteinov po 24-urni, kot tudi 7-dnevni izpostavljenosti. S študijo smo pokazali, da tako etanol kot tudi acetaldehid v odvisnosti od njune koncentracije zmanjšata celično viabilnost. V študiji proliferacije sta etanol in acetaldehid, v odvisnosti od njunih koncentracij, značilno zmanjšala število celic po 7-dnevni izpostavljenosti. Pri ugotavljanju vsebnosti proteinov smo dobili bifazno krivuljo tako po 24-urni, kot tudi po 7-dnevni izpostavljenosti različnim koncentracijam etanola oziroma acetaldehida. Prisotnost AMT je signifi kantno zmanjšala učinek etanola na celično proliferacijo. Zaključimo lahko, da je dolgotrajna izpostavljenost astrocitov etanolu bolj toksična kot akutna. Acetaldehid je močnejši toksin kot etanol in vsaj del toksičnosti etanola je posledica delovanja njegovega prvega metabolita, acetaldehida

Characterizing the scent and chemical composition of Panthera leo marking fluid using solid-phase microextraction and multidimensional gas chromatography–mass spectrometry-olfactometry

Lions (Panthera leo) use chemical signaling to indicate health, reproductive status, and territorial ownership. To date, no study has reported on both scent and composition of marking fluid (MF) from P. leo. The objectives of this study were to: 1) develop a novel method for simultaneous chemical and scent identification of lion MF in its totality (urine + MF), 2) identify characteristic odorants responsible for the overall scent of MF as perceived by human panelists, and 3) compare the existing library of known odorous compounds characterized as eliciting behaviors in animals in order to understand potential functionality in lion behavior. Solid-phase microextraction and simultaneous chemical-sensory analyses with multidimensional gas-chromatography-mass spectrometry-olfactometry improved separating, isolating, and identifying mixed (MF, urine) compounds versus solvent-based extraction and chemical analyses. 2,5-Dimethylpyrazine, 4-methylphenol, and 3-methylcyclopentanone were isolated and identified as the compounds responsible for the characteristic odor of lion MF. Twenty-eight volatile organic compounds (VOCs) emitted from MF were identified, adding a new list of compounds previously unidentified in lion urine. New chemicals were identified in nine compound groups: ketones, aldehydes, amines, alcohols, aromatics, sulfur-containing compounds, phenyls, phenols, and volatile fatty acids. Twenty-three VOCs are known semiochemicals that are implicated in attraction, reproduction, and alarm-signaling behaviors in other species

Acute and chronic alcohol injections increase taurine in the nucleus accumbens.

Intracerebral microdialysis was used to investigate release of amino acid neurotransmitters in response to acute and chronic injection of alcohol in unanaesthetised animals. Increases in taurine levels but not of glutamate or GABA were found after acute injection of alcohol. Chronic injection of alcohol, in increasing doses over six weeks, resulted in substantially greater increases in taurine levels. Basal levels of all three amino acids were increased after chronic injection of alcohol, up to a dose of 2 g/kg body weight, but not at higher doses. Higher doses may overcome the compensatory capacity which induces increases concentrations of these neuromodulators after chronic exposure to alcohol

The nicotine + alcohol interoceptive drug state: contribution of the components and effects of varenicline in rats

RATIONALE: Nicotine and alcohol co-use is highly prevalent, and as such, individuals experience the interoceptive effects of both substances together. Therefore, examining sensitivity to a compound nicotine and alcohol (N+A) interoceptive cue is critical to broaden our understanding of mechanisms that may contribute to nicotine and alcohol co-use. OBJECTIVES: This work assessed the ability of a N+A interoceptive cue to gain control over goaltracking behavior and determined the effects of the α4β2 nicotinic partial agonist and smoking cessation compound varenicline on sensitivity to N+A. METHODS: Two groups of male Long-Evans rats were trained to discriminate N+A (0.4 mg/kg nicotine + 1 g/kg alcohol, IG) from water under two different training conditions using a Pavlovian drug discrimination task. The effects of varenicline (0, 1, 3 mg/kg, IP) administered alone and on sensitivity to N+A and the components were determined. RESULTS: Under both training conditions, N+A rapidly gained control over behavior, with a greater contribution of nicotine to the N+A compound cue. Varenicline fully substituted for the N+A training dose and varenicline (1 mg/kg) enhanced sensitivity to the lowest N+A dose (0.1N+0.1A). Given the high selectivity of varenicline for the α4β2 receptor, this finding suggests a functional role for α4β2 nicotinic acetylcholine receptors (nAChR) in modulating sensitivity to N+A. CONCLUSIONS: The N+A compound cue is a unique cue that is modulated in part, by activity at the α4β2 nAChR. These findings advance understanding of the interoceptive effects of nicotine and alcohol in combination and may have implications in relation to their co-use