期刊
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
卷 44, 期 7, 页码 668-677出版社
WILEY
DOI: 10.1111/eci.12285
关键词
Apoptotic signalling; bioenergetics; exercise; liver toxicity; nonsteroid anti-inflammatory drugs; oxidative stress
资金
- Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/89807/2012, SFRH/BD36626/2007, SFRH/BD/61889/2009, SFRH/BPD/66935/2009, SFRH/BPD/4225/2007]
- Muscletech Network [MTN20100101]
- Plan Nacional I+D+I [DEP2010-22205-C02-01]
- FCT [PTDC/DES/113580/2009 - FCOMP-01-0124-FEDER-014705]
- [PEst-OE/SAU/UI0617/2011]
- [Pest-C/SAU/LA0001/2013-2014]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/61889/2009] Funding Source: FCT
Background Several strategies have been developed to counteract liver injury as a consequence of nonsteroid anti-inflammatory drugs toxicity. Here, we aimed to determine whether physical exercise results in liver mitochondrial protection against in vitro diclofenac toxicity. Material and methods Male adult Sprague-Dawley rats were divided into sedentary, 12-week endurance training (ET) and voluntary activity (VPA). In vitro liver mitochondrial function as assessed by oxygen consumption, transmembrane electric potential () and susceptibility to the mitochondrial permeability transition pore (MPTP) was evaluated in the absence and presence of diclofenac. Mitochondrial oxidative stress markers [MnSOD, aconitase, -SH and MDA, SIRT3, p66shc(Ser36)/p66shc ratio] and apoptotic signalling (caspases 3, 8 and 9, Bax, Bcl-2 and CypD) were assessed. Content of OXPHOS components and qualitative liver morphological evaluation were assessed. Results Despite no effects of ET and VPA on basal liver mitochondrial oxygen consumption or endpoints, exercised animals showed lower susceptibility to MPTP. Diclofenac-induced decrease in , increased state 4 respiration and susceptibility to MPTP opening were all prevented by exercise. Under untreated conditions, VPA group showed higher aconitase activity, while ET decreased MDA and increased Bax content. VPA decreased p66shc(Ser36), complex III and V OXPHOS subunits. Both ET and VPA increased complex IV OXPHOS subunit, and SIRT3 and Bcl-2 content and decreased caspase 9 activity. Unexpectedly, ET and VPA decreased ANT. Conclusions 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.
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