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An experimental study on the role of naloxone in facilitating alcohol metabolism in acute alcohol intoxication rats

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<p>Naloxone has been used in acute alcohol intoxication (AAI) in China and some other Asian countries.

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However, the effects of naloxone on alcohol metabolism and its mechanisms are unclear. This study aimed to explore the role of naloxone in facilitating alcohol metabolism.</p> <p>AAI rat model was established by force-feeding alcohol.

The effect of naloxone in facilitating alcohol metabolism was detected using an improved breathalyzer. The open field test (OFT) was also used to observe the behavioral changes in rats.</p> <p>By breathalyzer, naloxone could promote alcohol metabolism in a dose-dependent manner. Naloxone could promote the arousal of rats and increase the spontaneous activity of rats.

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But Cytochrome P450 2E1 (CYP2E1) protein and mRNA showed no significant changes. Naloxone promotes alcohol metabolism, and the changing trend of blood alcohol concentration shows a good pharmacokinetics-pharmacodynamics (PK-PD) correlation with adrenocorticotropic hormone (ACTH) expression and behavioral changes in rats.</p> <p>We established a method via gas collection bottles to evaluate the metabolic activity of CYP2E1 and alcohol dehydrogenase (ADH) in rats and established a metabolic model reflecting the changes in segmented alcohol concentrations over time.

Naloxone could promote alcohol metabolism by promoting arousal, which is beneficial to AAI.</p> <p>Breathalyzers have been used by traffic police for roadside enforcement for many years. By measuring the breath alcohol concentration, the device automatically converts it into a blood alcohol concentration. However, using this noninvasive, simple, and highly operable device to measure blood alcohol concentration in rats has long been a challenge.

In this study, we used a gas collection bottle to collect the exhaled breath of rats over a 10-min period and optimized the method for measuring exhaled alcohol concentration (automatically converted to blood alcohol concentration) using a breathalyzer equipped with a built-in suction pump. Gas chromatography was adopted to detect the effect of naloxone facilitating alcohol metabolism to verify the reliability and feasibility of the breathalyzer method.

Furthermore, we established a segmented alcohol kinetic model, which effectively assessed alcohol metabolism activity (primarily Cytochrome P450 2E1 and alcohol dehydrogenase activity). Using this method, we evaluated the potential of naloxone to promote alcohol metabolism activity and analyzed the possible mechanism: promoting adrenocorticotropic hormone (ACTH) production, enhancing arousal, and increasing alcohol metabolism activity, rather than acting at the level of enzymatic protein or transcription.

In addition, through behavioral experiments, we analyzed the promoting effect of naloxone on spontaneous activity in rats with acute alcohol intoxication, further confirming that the possible mechanism by which naloxone promotes alcohol metabolism activity involves promoting arousal and restoring cardiovascular and liver function. Naloxone promotes alcohol metabolism, and the trend of changes in blood alcohol concentration shows a good pharmacokinetics-pharmacodynamics correlation with ACTH expression and behavioral changes in rats.</p> <p>Naloxone can promote the arousal of rats with acute alcohol intoxication.</p> <p>Naloxone could enhance metabolic activities of Cytochrome P450 2E1 and Alcohol dehydrogenase in rats.</p> <p>Naloxone on promoting alcohol metabolism in rats may be related to the increase of adrenocorticotropic hormone.</p> <p>Alcohol metabolism showed significant sex differences with or without naloxone, and female rats outperformed male rats.</p>

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