Trehalose attenuates renal ischemia-reperfusion injury by enhancing autophagy and inhibiting oxidative stress and inflammation.

Renal ischemia-reperfusion injury (IRI) is one of the most common acute kidney injuries, there is still a lack of effective treatment in the clinical setting. Trehalose (Tre), a naturally disaccharide, has been demonstrated to protect against oxidative stress, inflammation, and apoptosis. However, whether it could protect against IR-induced renal injury needs to be investigated. In an in vivo experiment, C57BL/6J mice were pretreated with or without Tre (2 g/kg) through a daily single intraperitoneal injection for 3 days before renal IR surgery. Renal function, apoptosis, oxidative stress, and inflammation were analyzed to evaluate kidney injury. In in vitro experiment, mouse proximal tubular cells were treated with or without Tre under a hypoxia-reoxygenation (H/R) condition. Western blotting, autophagy flux detection, and apoptosis assay were performed to evaluate the level of autophagy and the anti-apoptosis effect of Tre. The in vivo results showed that the renal damage induced by IR was ameliorated by Tre treatment, as the renal histology and renal function were improved and the enhanced protein levels of kidney injury molecule 1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were blocked. Moreover, autophagy was activated by Tre pretreatment along with inhibition of the IRI-induced apoptosis, oxidative stress, and inflammation. The in vitro results showed that Tre treatment activated autophagy and protected against H/R-induced tubular cell apoptosis and oxidative stress. Our results demonstrated that Tre protects against IR-induced renal injury, possibly by enhancing autophagy and blocking oxidative stress, inflammation, and apoptosis, suggesting its potential use for the clinical treatment of renal IRI.