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

Abstract

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.

Hyperglycemia‐Triggered Sphingosine‐1‐Phosphate and Sphingosine‐1‐Phosphate Receptor 3 Signaling Worsens Liver Ischemia/Reperfusion Injury by Regulating M1/M2 Polarization

“…The roles of S1PR3 in IRI may be organ specific, which is perhaps related to cell‐specific expression of S1PR3 . Previous studies have shown that DM increases susceptibility to IRI and that inflammation is an important factor in diabetes . In this study, we found that the S1P/S1PR3 pathway was activated in the KCs of hyperglycemic mice and that CAY10444 could suppress hepatocellular injury and inflammation after IR in STZ‐treated mice but not in control mice.…”

“…Overwhelming epidemiological and clinical data have demonstrated that patients with DM are more sensitive to IRI . Diabetes and its associated hyperglycemia are involved in a variety of ischemic tissue injuries, including in the lungs, brain, kidney, and liver . The numerous functions of S1P include the regulation of cell death, proliferation, motility, differentiation, and inflammation .…”

“…(28) Diabetes and its associated hyperglycemia are involved in a variety of ischemic tissue injuries, including in the lungs, brain, kidney, and liver. (29)(30)(31)(32) The numerous functions of S1P include the regulation of cell death, proliferation, motility, differentiation, and inf lammation. (33)(34)(35) Most of the effects of S1P are mediated through the S1PR family, which includes the ubiquitously expressed S1PR1, S1PR2, and S1PR3 subtypes.…”

Efficacy of an artificial pancreas device for achieving tight perioperative glycemic control in living donor liver transplantation

“…Hyperglycemia has been reported to be associated with impaired vasodilation, the suppressed expression of the nitric oxide synthetase gene, and a reduction in the circulating nitric oxide levels . Recently, Zhang et al reported that hyperglycemia aggravates hepatic ischemic reperfusion injury, which might be attributed to chronic oxidative stress and the possible malfunction of the antioxidative system . For these reasons, the reperfusion of the liver graft in patients with intraoperative hyperglycemia may lead to the development of more severe reperfusion injury of the liver.…”

The Antiapoptosis Effect of Glycyrrhizate on HepG2 Cells Induced by Hydrogen Peroxide

“…Chronic oxidative stress may also promote the onset or progression of chronic liver diseases including nonalcoholic fatty liver disease (NAFLD), cirrhosis, hepatitis, and hepatic carcinoma, which if not treated properly are likely to advance to end-stage liver diseases requiring surgical intervention [2]. Major sources of cellular ROS include the mitochondrial respiratory chain and enzymatic reactions mediated by enzyme systems such as xanthine oxidoreductase, nitric oxide (NO) synthase (NOS), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidases [3].…”