Assessment of diphenhydramine toxicity – Is its mode of action conserved between human and zebrafish?

Barreto, Ângela; Santos, Joana; Capitão, Ana; Rodrigo, Eusébio,; Damasceno, Évila Pinheiro; Machado, Ana Luísa; Rocha, Luciana S.; Calisto, Vânia; Amorim, Mónica J.B.; Maria, V.L.

doi:10.1016/j.envint.2022.107263

Cited by 12 publications

(5 citation statements)

References 64 publications

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“…It has been suggested that the correlation of membrane-based transporters and their binding to plasma proteins can affect the distribution of APIs between water and fish plasma. 4 CMZ binding to plasma proteins is not conducive to its transport to muscle. Alexishvili et al.…”

Section: Discussionmentioning

confidence: 95%

“… 2 The biological effects of several human APIs, such as psychiatric medications, on fish have been found to be similar to those of their mode of action (MOA). 3 , 4 , 5 The read-across hypothesis states that pharmacological effects of the drug on non-targeted organisms are observed when the concentration of the drug in non-targeted biological plasma is equal to the human therapeutic plasma concentration (H T PC), provided that the molecular target (usually a receptor or enzyme) is conserved. 2 , 6 Several studies 7 , 8 , 9 have demonstrated the evolutionary conservation of some protein targets of drugs that are structurally and functionally conserved in zebrafish ( Danio rerio ) and other aquatic species.…”

Section: Introductionmentioning

confidence: 99%

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Effects of carbamazepine on the central nervous system of zebrafish at human therapeutic plasma levels

Yang,

Bao,

Hao

et al. 2023

iScience

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Effects of carbamazepine on the central nervous system of zebrafish at human therapeutic plasma levels

Yang,

Bao,

Hao

et al. 2023

iScience

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“…Se ha tratado de establecer, por medio de estudios retrospectivos y prospectivos, la relación entre la dosis ingerida y las manifestaciones clínicas en contexto de intoxicación. En particular, hay un umbral de dosis de 1 gr para la aparición de síntomas severos como delirium o psicosis, convulsiones, arritmias y coma 10 . Sin embargo, con dosis de 500 mg se pueden presentar síntomas menores y moderados, prolongaciones del complejo QRS y el intervalo QTc en casos con factores de riesgo cardiovascular, por lo cual las dosis de 500 mg requieren monitorización electrocardiográfica continua 9 .…”

Section: Discussionunclassified

Uso de emulsiones lipídicas en el tratamiento exitoso de un caso de intoxicación por difenhidramina

Angulo¹,

Arias²,

Pérez

2022

medupb

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La difenhidramina tiene efectos antihistamínico anti-H1 específico y antimuscarínico que pueden ocasionar un desenlace fatal según la dosis total ingerida. Se reporta un caso de intoxicación por difenhidramina tratado de forma exitosa con emulsiones lipídicas a pesar de ingesta de dosis letal. Se presenta el caso de un paciente de 19 años que ingresó por intoxicación por difenhidramina a dosis de 25 mg/kg (1.5 g) después del tiempo de descontaminación, con toxidrome anticolinérgico, con neurotoxicidad, cardiotoxicidad (QRS y QT prolongados) y sin respuesta al enfoque inicial, se iniciaron emulsiones lipídicas y, a su vez, se logró alta temprana por evolución clínica favorable y resolución de la prolongación del intervalo QTc y del cuadro anticolinérgico. La emulsión lipídica es una opción terapéutica para disminuir la morbimortalidad y la estancia hospitalaria por contrarrestar la cardiotoxicidad y neurotoxicidad producidas por moléculas lipofílicas como la difenhidramina.

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“…A lot of data on the effects of various chemical agents added to water on the zebrafish heart rate have been published to date. Often, exposures to toxicants lead to a decrease in heart rate (Barreto et al, 2022;Cui et al, 2022;Yu et al, 2022). Increased heart rate in response to the addition of chemicals to water was also described (Shabnam and Philip, 2018;Li et al, 2019;.…”

Section: Discussionmentioning

confidence: 99%

Influence of hypomagnetic field on the heartbeat in zebrafish embryos

Крылов

Мачихин²,

Sizov³

et al. 2022

Front. Physiol.

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The magnetic environment may influence the functioning of the cardiovascular system. It was reported that low-frequency and static magnetic fields affect hemodynamics, heart rate, and heart rate variability in animals and humans. Moreover, recent data suggest that magnetic fields affect the circadian rhythms of physiological processes. The influence of the magnetic environment on heart functionating during early development has been studied insufficiently. We utilized transparent zebrafish embryos to evaluate the effect of the hypomagnetic field on the characteristics of cardiac function using a noninvasive optical approach based on photoplethysmographic microscopic imaging. The embryos were exposed to the geomagnetic and hypomagnetic fields from the second to the 116th hour post fertilization under a 16 h light/8 h dark cycle or constant illumination. The exposure of embryos to the hypomagnetic field in both lighting modes led to increased embryo mortality, the appearance of abnormal phenotypes, and a significant increase in the embryo’s heartbeat rate. The difference between maximal and minimal heartbeat intervals, maximal to minimal heartbeat intervals ratio, and the coefficient of variation of heartbeat rate were increased in the embryos exposed to the hypomagnetic field under constant illumination from 96 to 116 h post fertilization. The dynamics of heartbeat rate changes followed a circadian pattern in all studied groups except zebrafish exposed to the hypomagnetic field under constant illumination. The results demonstrate the importance of natural magnetic background for the early development of zebrafish. The possible mechanisms of observed effects are discussed.

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Assessment of diphenhydramine toxicity – Is its mode of action conserved between human and zebrafish?

Cited by 12 publications

References 64 publications

Effects of carbamazepine on the central nervous system of zebrafish at human therapeutic plasma levels

Effects of carbamazepine on the central nervous system of zebrafish at human therapeutic plasma levels

Uso de emulsiones lipídicas en el tratamiento exitoso de un caso de intoxicación por difenhidramina

Influence of hypomagnetic field on the heartbeat in zebrafish embryos

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