Endurance training and chronic intermittent hypoxia modulate in vitro salicylate-induced hepatic mitochondrial dysfunction.
Mitochondrial function is modulated by multiple approaches including physical activity, which can afford cross-tolerance against a variety of insults. We therefore aimed to analyze the effects of endurance-training (ET) and chronic-intermittent hypobaric-hypoxia (IHH) on liver mitochondrial bioenergetics and whether these effects translate into benefits against in vitro salicylate mitochondrial toxicity. Twenty-eight young-adult male rats were divided into normoxic-sedentary (NS), normoxic-exercised (NE), hypoxic-sedentary (HS) and hypoxic-exercised (HE). ET consisted of 1h/days of treadmill running and IHH of simulated atmospheric pressure of 49.3 kPa 5h/days during 5weeks. Liver mitochondrial oxygen consumption, transmembrane-electric potential (ΔΨ) and permeability transition pore induction (MPTP) were evaluated in the presence and absence of salicylate. Aconitase, MnSOD, caspase-3 and 8 activities, SH, MDA, SIRT3, Cyp D, HSP70, and OXPHOS subunit contents were assessed. ET and IHH decreased basal mitochondrial state-3 and state-4 respiration, although no alterations were observed in ΔΨ endpoints evaluated in control mitochondria. In the presence of salicylate, ET and IHH decreased state-4 and lag-phase of ADP-phosphorylation. Moreover, ADP-lag phase in hypoxic was further lower than in normoxic groups. Neither ET nor IHH altered the susceptibility to calcium-induced MPTP. IHH lowered MnSOD and increased aconitase activities. ET and IHH decreased caspase 8 activity whereas no effect was observed on caspase 3. The levels of SIRT3 increased with ET and IHH and Cyp D decreased with IHH. Data suggest that ET and IHH do not alter general basal liver mitochondrial function, but may attenuate some adverse effects of salicylate.
Research Centre in Physical Activity, Health and Leisure, Faculty of Sport, University of Porto, Portugal. aascensao@fade.up.pt
A
A
Ascensão
I O
IO
Gonçalves
J
J
Lumini-Oliveira
I
I
Marques-Aleixo
E
E
Dos Passos
S
S
Rocha-Rodrigues
N G
NG
Machado
A C
AC
Moreira
P J
PJ
Oliveira
J R
JR
Torrella
J
J
Magalhães
D000818:Animals; D000860:Hypoxia; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000187:drug effects / Q000502:physiology; D024101:Mitochondrial Proteins / Q000032:analysis; D010101:Oxygen Consumption; D010805:Physical Conditioning, Animal; D051381:Rats; D012459:Salicylates / Q000633:toxicity*
D024101:Mitochondrial Proteins; D012459:Salicylates