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J Cell Physiol. 2018 Nov;233(11):8677-8690. doi: 10.1002/jcp.26747. Epub 2018 May 15.

Zinc mitigates renal ischemia-reperfusion injury in rats by modulating oxidative stress, endoplasmic reticulum stress, and autophagy.

Author information

1
Faculty of Pharmacy, Department of Physiology, Unité de Biologie et Anthropologie Moléculaire Appliquées au Développement et à la Santé, University of Monastir, Monastir, Tunisia.
2
Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas, Liver Unit Hospital Clínici Provincial, IDIBAPS and CIBERehd, Barcelona, Spain.
3
Laboratoire de Génétique, Biodiversité et Valorisation des Bioressources (LR11ES41), Institute of Biotechnology, University of Monastir, Monastir, Tunisia.

Abstract

Oxidative stress is a major factor involved in the pathogenesis of renal ischemia/reperfusion (I/R). Exogenous zinc (Zn) was suggested as a potent antioxidant; however, the mechanism by which it strengthens the organ resistance against the effects of reactive oxygen species (ROS) is not yet investigated. The present study aims to determine whether acute zinc chloride (ZnCl2 ) administration could attenuate endoplasmic reticulum (ER) stress, autophagy, and inflammation after renal I/R. Rats were subjected to either sham operation (Sham group, n = 6), or 1 hr of bilateral ischemia followed by 2 hr of reperfusion (I/R groups, n = 6), or they received ZnCl2 orally 24 hr and 30 min before ischemia (ZnCl2 group, n = 6). Rats were subjected to 1 hr of bilateral renal ischemia followed by 2 hr of reperfusion (I/R group, n = 6). Our results showed that ZnCl2 enhances renal function and reduces cytolysis (p < 0,05). In addition, it increased significantly the activities of antioxidant enzymes (SOD, CAT, and GPX) and the level of GSH in comparison to I/R (p < 0,05). Interestingly, ZnCl2 treatment resulted in significant decreased ER stress, as reflected by GRP78, ATF-6,p-eIF-2α, XPB-1, and CHOP downregulaion. Rats undergoing ZnCl2 treatment demonstrated a low expression of autophagy parameters (Beclin-1 and LAMP-2), which was correlated with low induction of apoptosis (caspase-9, caspase-3, and p-JNK), and reduction of inflammation (IL-1ß, IL-6, and MCP-1) (p < 0,05). In conclusion, we demonstrated the potential effect of Zn supplementation to modulate ER pathway and autophagic process after I/R.

KEYWORDS:

Zinc; autophagy; endoplasmic; inflammation; ischemia/reperfusion; oxidative stress; reticulum stress

PMID:
29761825
DOI:
10.1002/jcp.26747

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