Preoperative fasting protects mice against hepatic ischemia/reperfusion injury: Mechanisms and Effects on liver regeneration

✍ Scribed by Ricky Harminder Bhogal; Barnaby Thomas Francis Stephenson; Simon Charles Afford

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 39 KB
• Volume: 17
• Category: Article
• ISSN: 1527-6465
• DOI: 10.1002/lt.22390

✦ Synopsis

We read with great interest the recent article by Verweij et al. 1 The authors ascribe the beneficial effects of preoperative fasting in reducing liver ischemia/reperfusion injury to the induction of heme oxygenase 1 and various antioxidants, including superoxide dismutase 2, glutathione peroxidase 1, and glutathione reductase. Other beneficial effects of preoperative fasting include the reduction of pselectin expression, the reduced production of proinflammatory cytokines, and the reduced generation of superoxide radicals after liver reperfusion. However, it is well known that starvation also induces the cellular process known as autophagy. This catabolic process involves the degradation of a cell's own components through the resident lysosomal machinery. 2 With respect to Verweij et al.'s work, the specific autophagic process known as macroautophagy is particularly interesting. 2 In this process, damaged organelles and unused, long-lived proteins are sequestered in a double-membrane vesicle termed the autophagosome. This autophagosome is then able to fuse in the cytoplasm with a lysosome to form an autophagolysosome; the contents are then degraded via acidic lysosomal hydrolases. Moreover, during nutrient starvation, as described by Verweij et al., increased levels of autophagy or, more specifically, macroautophagy lead to the breakdown of nonvital cellular components and the release of nutrients, and this ensures that vital cellular processes can continue. 3 Here we present an example of how autophagy could also explain some of the authors' experimental results. Previous work has shown that the mitochondrion is the central generator of superoxide radicals in the cell. 4 Verweij et al. 1 have demonstrated that starvation decreases superoxide radical generation, and this is consistent with macroautophagy of damaged mitochondria. Indeed, autophagy-related protein 7, a regulatory autophagy protein, may be a key mediator of this nutrient-mediated autophagy. 5 Hence, the sequestration of damaged or dysfunctional mitochondria would allow increased cellular energy from the degraded organelle but also decrease cell death, as the authors have demonstrated. Therefore, although the authors have shown that the induction of antioxidants and heme oxygenase 1 underlies some of the benefits of preoperative fasting in reducing liver ischemia/reperfusion injury, the contributions made by other processes such as autophagy should not be forgotten.