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cc-by, (c) Santos, 2018
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/132048

Physical exercise as non-pharmacological tool to counteract drug-induced liver mitochondrial injury: effects on mitochondrial bioenergetics, oxidative stress, apoptosis, dynamics and auto (mito) phagy signalling markers

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[eng] Liver diseases resulting from the toxicity induced by frequent pharmacological drug consumption are among the main health problems of modern western societies. On the other hand, healthy life-style-based behaviors including physical exercise are critical for counteracting, by preventing and/or treating, the drug-associated deleterious consequences for the hepatic tissue. The present thesis aimed to study, in a rat model, the effects of two chronic physical exercise regimens on liver morphological, biochemical and functional features centered on mitochondria, as these subcellular network compartments are known as dynamic structures closely involved in important mechanisms related to both the physiopathology of the disease and the beneficial adaptations of tissues afforded by exercise. Functional alterations in liver mitochondria were measured in in vitro: respiratory-driven endpoints, susceptibility to permeability transition pore opening. Additionally, enzymatic activities and the expression of proteins involved in redox response, apoptotic cell death, mitochondrial biogenesis, dynamic and autophagic markers were analyzed throughout the experimental work comprised in this thesis. Basal mitochondrial responses to toxic drugs exposure, both after in vitro (diclofenac) and in vivo (doxorubicin) stimulation were determined. It was overall concluded that chronic physical exercise induced liver mitochondrial alterations suggestive of positive remodeling, which were translated in a resultant more resistant phenotype against the in vitro toxicity of diclofenac and the in vivo harmful effects of doxorubicin. The observed mitigation effects were associated with favorable modifications in functional endpoints of mitochondrial respiration and in key signaling proteins related to oxidative stress and damage, apoptosis, mitochondrial biogenesis and dynamics, and auto(mito)phagy-related quality control mechanisms.

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SANTOS ALVES, Estela. Physical exercise as non-pharmacological tool to counteract drug-induced liver mitochondrial injury: effects on mitochondrial bioenergetics, oxidative stress, apoptosis, dynamics and auto (mito) phagy signalling markers. [consulta: 23 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/132048]

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