Chu 2016 World J Gastroenterol

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Chu MJ, Premkumar R, Hickey AJ, Jiang Y, Delahunt B, Phillips AR, Bartlett A (2016) Steatotic livers are susceptible to normothermic ischemia-reperfusion injury from mitochondrial Complex-I dysfunction. World J Gastroenterol 22:4673-84.

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Chu MJ, Premkumar R, Hickey AJ, Jiang Y, Delahunt B, Phillips AR, Bartlett A (2016) World J Gastroenterol

Abstract: To assess effects of ischemic preconditioning (IPC, 10-min ischemia/10-min reperfusion) on steatotic liver mitochondrial function after normothermic ischemia-reperfusion injury (IRI).

Sixty male Sprague-Dawley rats were fed 8-wk with either control chow or high-fat/high-sucrose diet inducing > 60% mixed steatosis. Three groups (n = 10/group) for each dietary state were tested: (1) IRI group underwent 60 min partial hepatic ischemia and 4 h reperfusion; and (2) IPC group underwent IPC prior to same standard IRI, iii) Sham underwent the same surgery without IRI or IPC. Hepatic mitochondrial function were analysed by oxygraphs. Mitochondrial Complex-I, Complex-II enzyme activity, serum alanine transferase (ALT) and histological injury were measured.

Steatotic-IRI livers had a greater increase in ALT (2476 ± 166 vs 1457 ± 103 IU/L, P < 0.01) and histological injury following IRI compared to the lean liver group. Steatotic-IRI demonstrated lower Complex-I activity at baseline [78.4 ± 2.5 vs 116.4 ± 6.0 nmol/(min.mg protein), P < 0.001] and following IRI [28.0 ± 6.2 vs 104.3 ± 12.6 nmol/(min.mg protein), P < 0.001]. Steatotic-IRI also demonstrated impaired Complex-I function post-IRI compared to the lean liver IRI group. Complex-II activity was unaffected by hepatic steatosis or IRI. Lean liver mitochondrial function was unchanged following IRI. IPC normalized ALT and histological injury in steatotic livers but had no effect on overall steatotic liver mitochondrial function or individual mitochondrial complex enzyme activities.

Warm IRI impairs steatotic liver Complex-I activity and function. The protective effects of IPC in steatotic livers may not be mediated through mitochondria.

Keywords: Mitochondrial respiration, Fatty liver, Liver ischemia, Oxidative phosphorylation, Liver injury, Hepatic steatosis, Ischemic preconditioning

O2k-Network Lab: NZ Auckland Hickey AJ


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Obesity, Other  Stress:Ischemia-reperfusion  Organism: Rat  Tissue;cell: Liver  Preparation: Homogenate 


Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k 

2016-04 

Correction

An Oroboros O2k was used in this publication, whereas the Anton Paar/Oroboros Oxygraph was the first-generation instrument for high-resolution respirometry, which was replaced by the O2k in 2002.