Distribution and pharmacokinetics of double-radiolabeled endotoxin in the rat brain and peripheral organs

Abstract

The endotoxin, lipopolysaccharide (LPS), of Salmonella typhimurium was biosynthetically labeled with (3)H and (14)C incorporated into the fatty acyl chains and glucosamine residues, respectively. The radio-labeled LPS was isolated from the bacteria and then injected into Sprague-Dawley rats. The distribution of (14)C and (3)H-LPS in plasma and other organs was determined following intraperitoneal (IP) doses of (14)C and (3)H-LPS (200 μg/kg). Plasma concentrations of both fatty acyl chains and glucosamine residues were biphasic, with a relatively rapid decay followed by a slow decline for 48 h. Similar biphasic results were found in the peripheral organs (kidney and heart) and brain barrier tissues (meninges and choroid plexus). In other brain tissues (brain stem, caudate nucleus, hypothalamus, frontal cortex, cerebellum and hippocampus), the glucosamine residue was biphasic, whereas the fatty acyl chains showed accumulation. Highest concentrations of LPS were found in the plasma, spleen and the liver. In addition, in the liver, sustained elevations of (14)C-glucosamine and (3)H-fatty acyl chains were observed. This indicates LPS accumulation in the liver. By contrast, the spleen showed biphasic decay of glucosamine residues and accumulation of fatty acyl chains. In the brain barrier tissues, peak LPS concentrations were significantly reduced (about 70%) and were further reduced (about 95%) in other brain tissues. The high elevation of LPS in the spleen is considered indicative of an immune response. Our findings highlight the potential significant role of lipid A as shown with the sustained elevation of (3)H-fatty acyl chains in the brain.

Histological effects and pharmacokinetics of lipopolysaccharide derived from Porphyromonas gingivalis on rat maxilla and liver concerning with progression into non‐alcoholic steatohepatitis

“…In comparison, the highest level of radioactivity in the organs (brain, liver, spleen, and kidney) was observed in the liver through 24 hours (Figure B). The present result clearly indicates that the pharmacokinetics of R‐LPS radioactivity from P. gingivalis in the liver was analogous to that from S. typhimurium . The R‐LPS radioactivity in the liver of HD/LPS (+) rats was the highest after 60 minutes, and at 35% was significantly higher than that of BD/LPS (+) rats even after 24 hours(Table ).…”

“…LPS is composed of a long carbohydrate chain (O‐antigen), a core polysaccharide and lipid A. Lipid A has chains of fatty acids attached to a disaccharide. Kim et al . confirmed that the 3 H‐fatty acid and 14 C‐glucosamine regions of lipid A in S. typhimurium ‐LPS were biosynthesized using 3 H‐sodium acetate and 14 C‐N‐acetyl‐D‐glucosamine as a precursor, respectively.…”

“…Unlabeled LPS was extracted from P. gingivalis (strain W83) grown in soybean‐casein digest (SCD) medium (soybean‐casein digest (SCD) medium, Nihon Pharmaceutical Co., Ltd., Tokyo, Japan). R‐LPS was biosynthesized in P. gingivalis with [2‐ 3 H] sodium acetate (740 GBq/mmol) ([2‐ 3 H] sodium acetate, American Radiolabeled Chemicals, Inc, St. Louis, M I) and N‐acetyl‐D‐[1‐ 14 C] glucosamine (1.85 GBq/mmol) (N‐acetyl‐D‐[1‐ 14 C] glucosamine, PerkinElmer,Waltham, MA) in the same SCD medium, according to the method of Kim et al …”

“…On the other hand, few studies have focused on the in vivo dynamics of LPS. Recently, Kim et al . reported that intraperitoneally injected radiolabeled LPS from Salmonella typhimurium accumulated in the liver of rats.…”

Effects of docosahexaenoic acid on locomotor activity in ethanol-treated HIV-1 transgenic rats

“…Through both paracellular and transcellular mechanisms, Tat and gpl20 HIV-1 viral proteins can alter BBB integrity and function (McRae 2016), and these effects might allow binge EtOH-induced elevations of plasma endotoxin to leak into brain tissues. Endotoxin in the brain can be degraded into fatty acid and glucosamine residues, which can penetrate into brain tissues (Kim et al 2014). Thus, there might be a “positive feedback” mechanism underlying how persistent HIV-1 proteins promote elevated plasma endotoxin leakage into the brain tissues, particularly following repeated binge exposure to EtOH.…”