Hepatic glutamine metabolism in the septic rat

Abstract

1. The hepatic metabolism of glutamine, alanine, ammonia, urea, glutathione and glucose was studied in rats made septic by caecal ligation and puncture and was compared with that in rats that had undergone sham operation (laparotomy). 2. Sepsis resulted in increases in the plasma activities of gamma-glutamyltransferase (P less than 0.001), alanine aminotransferase (P less than 0.001) and aspartate aminotransferase (P less than 0.001), the serum total and direct bilirubin concentrations (P less than 0.001), and the blood lactate (P less than 0.01), glutamine (P less than 0.05), alanine (P less than 0.001) and urea (P less than 0.05) concentrations, but produced decreases in the blood ketone body (P less than 0.001) and glutathione (P less than 0.05) concentrations and in the plasma cholesterol concentration (P less than 0.05). These changes were associated with marked negative nitrogen balance in septic rats. 3. Sepsis increased total hepatic blood flow (by 22.7%) together with hepatic arterial flow (by 25.8%) and portal venous flow (by 18.7%). Sepsis resulted in marked increases in the net rates of hepatic extraction of glutamine (by 164%), alanine (by 138%) and ammonia (by 259%) with concomitant increases in the net rates of hepatic release of glutamate (by 105%), glutathione (by 87.5%), glucose (by 70.1%) and urea (by 100.4%). 4. Sepsis increased the activities of liver carbamoylphosphate synthase (by 16.4%), ornithine transcarbamylase (by 29.8%), argininosuccinate synthase (by 28.1%) and arginase (by 33.8%). 5. Septic rats exhibited marked increases in hepatic protein (by 46.0%), RNA (by 43.4%) and DNA (by 37.7%) contents. These changes were accompanied by marked increases in the activity of thymidine kinase (by 35.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Sequential changes in in vivo muscle and liver protein synthesis and plasma and tissue glutamine levels in sepsis in the rat

“…Glutamine metabolism in the liver has been shown to be essential for the maintenance of ammonia and bicarbonate homoeostasis [44]. The hepatic extraction of glutamine is increased in sepsis, possibly due to an effect of the pro-inflammatory cytokines tumour necrosis factor α and interleukin-6 [43,45]. This is associated with a concomitant increase in the net release of glutamate, glutathione, glucose and urea [43].…”

“…The hepatic extraction of glutamine is increased in sepsis, possibly due to an effect of the pro-inflammatory cytokines tumour necrosis factor α and interleukin-6 [43,45]. This is associated with a concomitant increase in the net release of glutamate, glutathione, glucose and urea [43]. Glutathione is an important antioxidant produced from glutamine that may have a vital role in protective responses to sepsis and shock [46].…”

“…Of interest, however, is the fact that liver glutamine levels were unchanged following CLP. In the liver, glutamine is utilized for the synthesis of urea and glutathione, and as a substrate for gluconeogenesis [42,43]. Hepatic glutaminase activity is increased during starvation, diabetes and consumption of a high-protein diet [42].…”

Does Neutrophil-Mediated Oxidative Stress Play Any Significant Role in Producing Hepatocellular Dysfunction During Early Sepsis?

“…Similarly, a decrease in reduced glutathione and an increase in lipid peroxidation were also observed in the lungs following endotoxin challenge [35]. In addition, hepatic glutathione levels were reduced by 45% following acute infection [36], which was accompanied by an increased net rate of hepatic release of glutathione during sepsis [37]. Moreover, glutathione deficiency increases organ dysfunction following hemorrhagic shock [38].…”

Normal Serum Alanine Concentration Differentiates Transient Neonatal Lactic Acidemia from an Inborn Error of Energy Metabolism

“…Seizures due to hypoxic brain injury result in transient elevation of lactic acid, alanine and glutamate in neonatal rats [8] . Lactic acidosis and a marked increase in serum alanine concentrations have also been described in association with sepsis [9] . Young infants of HIV-infected mothers exposed to nucleoside analogues frequently develop reversible lactic acidemia with the elevation of serum alanine concentration [10] .…”