Hyperglycemia induced by glucose infusion causes hepatic oxidative stress and systemic inflammation, but not STAT3 or MAP kinase activation in liver in rats

Abstract

The purpose of this study was to determine the effects of acute hyperglycemia induced by glucose infusion on oxidative stress, systemic inflammation, and several key signal intermediates in liver for the systemic inflammatory response in nonstressed rats. Rats received saline or glucose infusion (hyperglycemic clamp) for 3 hours. Rats without catheter insertion were included as an additional control for observing the effects of surgical stress. Levels of malondialdehyde (MDA) and total glutathione to assess oxidative stress were determined in liver and muscle. Proinflammatory cytokines including tumor necrosis factor (TNF), interleukin (IL)-1 and IL-6, and alpha 1 acid glycoprotein (alpha1-AG) were determined in serum. The protein content and phosphorylation of extracellular signal-regulated kinase (ERK)1/2, p38 stress-activated protein kinase (p38), and signal transducer and activator of transcription-3 (STAT-3) were examined in the liver tissue with or without IL-6 stimulation. The results showed that acute hyperglycemia significantly increased MDA release and depleted total glutathione in liver but not in muscle. Hyperglycemia also significantly elevated the production of TNF, IL-1, and alpha1-AG, but not IL-6 in serum. However, hyperglycemia for 3 hours in vivo did not activate ERK1/2, p38 and STAT3 in liver, and also did not alter the response of these signal proteins to IL-6 stimulation. These data suggest that acute (3 hours) hyperglycemia causes hepatic oxidative stress and activates a low-grade systemic inflammation but does not affect key components of the IL-6 signaling pathway in liver.