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Oxidative Medicine and Cellular Longevity
Volume 2016, Article ID 3919627, 16 pages
Research Article

Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

1Department of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China
2Department of Thyroid and Breast Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China

Received 16 April 2016; Revised 28 June 2016; Accepted 12 July 2016

Academic Editor: Ruchi Shah

Copyright © 2016 Yihan Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI) and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R) after high (25 mM) or low (5.5 mM) glucose culture. Cell viability, reactive oxygen species (ROS), and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB) were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC) or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.