RESUMEN
Alcohol, or ethanol, is a major contributor to detrimental diseases and comorbidities worldwide. Alcohol use during pregnancy intervenes the developing embryos leading to morphological changes, neurocognitive defects, and behavioral changes known as fetal alcohol spectrum disorder (FASD). Zebrafish have been used as a model to study FASD; however, the mechanism and the impact of ethanol on oxidative stress and inflammation in the zebrafish FASD model remain unexplored. Hence, we exposed zebrafish embryos to different concentrations of ethanol (0â¯%, 0.5â¯%, 1.0â¯%, 1.25â¯%, and 1.5â¯% ethanol (v/v)) at 4-96â¯hours post-fertilization (hpf) to study and characterize the ethanol concentration for the FASD model to induce oxidative stress and inflammation. Here, we studied the survival rate and developmental toxicity parameters at different time points and measured oxidative stress, reactive oxygen species (ROS) generation, apoptosis, and pro-inflammatory gene expression in zebrafish larvae. Our findings indicate that ethanol causes various developmental abnormalities, including decreased survival rate, spontaneous tail coiling, hatching rate, heart rate, and body length, associated with increased malformation. Further, ethanol exposure induced oxidative stress by increasing lipid peroxidation and nitric oxide production and decreasing glutathione levels. Subsequently, ethanol increased ROS generation, apoptosis, and pro-inflammatory gene (TNF-α and IL-1ß) expression in ethanol exposed larvae. 1.25â¯% and 1.5â¯% ethanol had significant impacts on zebrafish larvae in all studied parameters. However, 1.5â¯% ethanol showed decreased survival rate and increased malformations. Overall, 1.25â¯% ethanol is the ideal concentration to study the oxidative stress and inflammation in the zebrafish FASD model.
Asunto(s)
Relación Dosis-Respuesta a Droga , Embrión no Mamífero , Etanol , Inflamación , Estrés Oxidativo , Pez Cebra , Animales , Estrés Oxidativo/efectos de los fármacos , Etanol/toxicidad , Embrión no Mamífero/efectos de los fármacos , Inflamación/inducido químicamente , Inflamación/patología , Trastornos del Espectro Alcohólico Fetal/patología , Especies Reactivas de Oxígeno/metabolismo , Modelos Animales de Enfermedad , Apoptosis/efectos de los fármacosRESUMEN
In recent years, mitochondria have gained significant interest in the field of biomedical research due to their impact on human health and ageing. As mitochondrial dynamics are strongly controlled by clock genes, misalignment of the circadian rhythm leads to adverse metabolic health effects. In this review, by exploring various aspects of research and potential links, we hope to update the current understanding of the intricate relationship between DRP1-mediated mitochondrial dynamics and changes in circadian rhythmicity leading to health issues. Thus, this review addresses the potential bidirectional relationships between DRP1-linked mitochondrial function and circadian rhythm misalignment, their impact on different metabolic pathways, and the potential therapeutics for metabolic and systemic disorders.