The response of liver albumin synthesis to infection in rats varies with the phase of the inflammatory process

Abstract

To discriminate between the effects of infection and of anorexia associated with infection, liver albumin synthesis was measured in well-fed rats, in rats injected with live Escherichia coli and in pair-fed rats at different stages of the inflammatory response (1, 6 and 10 days after infection) using a large dose of l-[1-(14)C]valine. Albuminaemia and albumin mRNA levels were unchanged following food restriction. However, absolute albumin synthesis was decreased in pair-fed rats compared with control animals after 1 day of food restriction, and had returned to normal values by day 10 when food intake was restored. Infection was characterized by a decrease in the plasma albumin concentration (35%, 45% and 28% as compared with pair-fed rats at 1, 6 and 10 days after infection respectively). Albumin mRNA levels and relative albumin synthesis were reduced in infected rats as compared with both control and pair-fed animals at all stages of infection. However, during the early acute response, the albumin absolute synthesis rate was similar in infected rats and pair-fed rats, indicating no specific effect of infection at this stage. Later in the course of infection, the amount of albumin synthesized by the liver was lower in infected than in pair-fed rats, and hypoalbuminaemia was probably maintained due to a lack of stimulation of synthesis despite increased food intake.

Albumin turnover: FcRn-mediated recycling saves as much albumin from degradation as the liver produces

“…Immunoadsorption (IA) was employed as an additional method for measuring the appearance rate of albumin and transferrin, modified from Ruot et al (31) with 3 H-labeled plasma from KO and WT mice at 90 min after administration of [ 3 H]leucine. Protein G-Sepharose (100 l; ϳ18 mg human IgG/ml drained beads; Amersham) was preequilibrated with Tris-buffered saline (TBS) and incubated with 100 l (1 mg/ml) of affinity-purified goat IgG against albumin or transferrin (Bethyl, Montgomery, TX) diluted in 200 l of TBS for 1 h at 4°C in an Ultrafree-MC centrifugal filter unit (Millipore, Billerica, MA) with gentle rocking.…”

Impact of Lipopolysaccharide-Induced Inflammation on the Disposition of the Aminocephalosporin Cefadroxil

“…Over the past half century, it has been reported that drug absorption and disposition can be altered during an inflammatory response because of modifications in plasma proteins, drug-metabolizing enzymes, and drug transporters (1). Downregulation of the levels of drug-binding plasma proteins and drug-metabolizing enzymes is now well identified, which translates into increased plasma drug concentrations or decreased clearance of drug substrates (2)(3)(4)(5)(6). More recently, inflammation-mediated regulation of drug transporters has been reported, especially for ATP-binding cassette (ABC) and solute carrier (SLC) transporters (1,5).…”

Dynamics of Albumin Synthetic Response to Intra-Abdominal Abscess in Patients with Gastrointestinal Fistula

“…In particular, a dynamic response (no change, a decrease, and then an increase) of albumin synthesis has been demonstrated in a rat model of sepsis [8]. Also, several studies in humans have shown a biphasic change of albumin synthesis in different phases of cholecystitis, which corresponds to studies in small animals.…”

“…Meanwhile, measurements of albumin synthesis in human beings have been conducted at only one time point, mostly during the acute phase, and several studies have addressed the possibility of albumin synthesis responding differently depending on the stage of the inflammatory process and various stimuli. In fact, a biphasic response (no change, then a decrease) of albumin synthesis has been confirmed in a rat model of sepsis [8]. The pathophysiologic process of intra-abdominal abscess following gastrointestinal fistula differs from those with an acute-phase response and possibly elicits different kinetics of albumin synthesis.…”