Exercise mitigates diclofenac‐induced liver mitochondrial dysfunction

Abstract

Both chronic physical exercise models augmented the resistance to in vitro diclofenac-induced mitochondrial alterations, including increased MPTP susceptibility, possibly by modulating oxidative stress and MPTP regulators.

Exercise modulates liver cellular and mitochondrial proteins related to quality control signaling

“…Complementarily to previously published data [3], a novel finding of the present work is that signaling markers of mitochondrial dynamics and autophagy are increased by both chronic exercise modalities, which suggest that these quality control-related processes are, at least in part, involved in liver plasticity and in the physiological adaptations that result in a more "energetically fit" and robust hepatic phenotype against the deleterious consequences of aging, metabolic diseases and drug-induced liver injury [1][2][3]8,15]. In the present study we did not test whether these particular exercise-related liver mitochondrial adaptations are also reproducible in models of obesity or other stressful pathological conditions to the liver.…”

“…In a complementary paper recently published by our group, we showed that chronic exercise induces adaptations in molecular and functional parameters associated with mitochondrial functionality, including respiratory fitness, permeability transition pore resistance, metabolic enzymes, oxidative stress and apoptotic signaling [3]. However, given the relevant interplay between mitochondrial dynamics and autophagic mechanisms in cellular and mitochondrial quality control and metabolism, the present work aimed at determining, for the first time, the effect of two distinct chronic exercise modalities on quality control-related liver protein signaling markers.…”

“…Accordingly, Samant et al [20] reported that SIRT3 promotes mitochondrial function not only by regulating the activity of metabolic enzymes, but also by regulating mitochondrial dynamics by targeting OPA1, since this fusion-related protein is hyperacetylated under pathological stress and the mitochondrial deacetylase SIRT3 was capable of deacetylating OPA1 and elevating its GTPase activity. Moreover, recent data from our laboratory suggest that chronic exercise-induced increased hepatic mitochondrial SIRT3 was accompanied by improved mitochondrial function and increased resistant to non-steroid anti-inflammatory drug-induced injury [8,21]. 5.…”

“…Moreover, as it has recently been demonstrated by our group [3], exercise-induced adaptations result in improved liver mitochondrial function, increasing the resistance to deleterious conditions such as drug-and obesity-related disorders [2,4]. However, emerging importance has been attributed to the interplay between mitochondrial biogenesis, dynamics and auto(mito)phagy in exercise-induced regulation of cellular adaptation to stress, although this was never explored in the context of the hepatic tissue.…”

“…However, emerging importance has been attributed to the interplay between mitochondrial biogenesis, dynamics and auto(mito)phagy in exercise-induced regulation of cellular adaptation to stress, although this was never explored in the context of the hepatic tissue. Therefore, in complement to the previously referred and published paper [3], the present work aimed to analyze the effects of two distinct physical exercise modalities (ET and VPA), which respectively intend to mimic systematic training programs and voluntary daily physical activity, on markers of mitochondrial biogenesis, fusion and fission, and autophagy. As autophagy and mitochondrial dynamics deregulation have been implicated in the pathogenesis of common liver diseases, since inadequate activation of mitochondrial repair processes may contribute to accumulation of mitochondrial damage [5], it is likely that the manipulation of these interrelated processes through exercise may hold potential therapeutic value.…”