Endotoxin stimulates hydrogen peroxide detoxifying activity in rat hepatic endothelial cells

Abstract

During endotoxemia, hepatic endothelial cells can be exThe study aimed to assess the effect of lipopolysacchaposed to oxidative stress, because sinusoidal endothelial cells ride (LPS) in vivo (from Escherichia coli, 2 mg/kg body are the first sites of neutrophil adhesion and are in direct weight intraperitoneally) on the production and elimicontact with activated Kupffer cells. 06 mol/L on endothelial cells after saline and LPS this reduced coenzyme is required for the functions of glutatreatment, respectively. No differences were detected in thione peroxidase (via glutathione) and for the stability of H 2 O 2 -stimulated fluorescence between resting and LPS-catalase.12,13 Therefore, the metabolism of glucose through stimulated Kupffer cells. Administration of varying glu-the HMS is potentially important for either the production cose concentrations in vitro significantly decreased the or the elimination of reactive oxygen species (ROS) in cells 14,15 However, lates the gene expression of GLUT1 glucose transporter, gene expression of Se-dependent glutathione peroxidase and glucose-6-phosphate dehydrogenase (G6PD), superoxide CuZn-dependent superoxide dismutase was elevated in endodismutases, and glutathione peroxidase in hepatic endo-thelial cells only. 15 The LPS-induced responses of these functhelial cells. The present data indicate that the LPS-in-tionally related genes of glucose metabolism and ROS-elimiduced metabolic alterations are accompanied by an nating pathways suggested that activated endothelial cells increased H 2 O 2 -detoxifying capacity in hepatic endothe-may have an increased capacity to metabolize hydrogen perlial cells. This may represent a protective mechanism oxide (H 2 O 2 ). Therefore, in the present study, we aimed to against exogenous oxidative stress caused by activated determine whether endotoxemia alters H 2 O 2 detoxifying achepatic phagocytes during inflammation. Our observa-tivity in freshly isolated hepatic endothelial and Kupffer tions are consistent with primed production of reactive cells. We investigated H 2 O 2 metabolism 22 hours after a sinoxygen species (ROS) in LPS-activated Kupffer cells. gle LPS injection intraperitoneally, because this treatment (HEPATOLOGY 1996;24:691-696.)caused alterations in the gene expression of glucose metabolic enzymes and ROS-eliminating pathways in a cell-specific fashion. 15 We also tested the effect of glucose availability and the potential involvement of nitric oxide on H 2 O 2 metabolism Abbreviations: HMS, hexose monophosphate shunt; NADPH, reduced nicotinamide adein these cells.nine dinucleotide phosphate; ROS, reactive oxygen species; LPS, lipopolysaccharide; DCFdiacetate, 2,7-dicholorfluorescin diacetate; L-NMMA, N G -monomethyl-L-arginine; PMA,

Endotoxemia, pentose cycle, and the oxidant/antioxidant balance in the hepatic sinusoid

“…Although LPS does not increase glutathione concentration significantly in endothelial cells, baseline cellular GSH content is about threefold greater in endothelial than Kupffer cells [14]. Moreover, after exogenous hydrogen peroxide challenge, recovery of reduced glutathione is faster and the concentration of cellassociated peroxides is attenuated in LPS-activated endothelial cells [14,53]. These facts reveal that, in endothelial cells, the elevated glucose uptake and primed HMS activity represent a functional support for the up-regulated NADPH-dependent ROS-detoxifying pathways during endotoxemia.…”

“…Nitric oxide may quench oxygen radicals, however, this gives rise to new reactive species, which eventually represent additional burden on ROS detoxifying pathways [19,44,52]. Arginine analogs inhibited HMS activity in resting macrophages, whereas they had no effect on zymosan-induced HMS activity [49] nor did they alter peroxide levels after subtoxic oxidative stress in hepatic endothelial cells [53]. Thus, when iNOS is induced, nitric oxide may alter the oxidant balance by targeting multiple sites of the HMS-dependent ROS metabolic pathways.…”

Experimental LPS-induced cholestasis alters subcellular distribution and affects colocalization of Mrp2 and Bsep proteins: A quantitative colocalization study

“…Rats were injected intraperitoneally with either LPS (2 mg/kg body weight) (Spolarics et al, 1996) or vehicle (physiological saline) as a control. LPS from Escherichia coli 055:B5 (Difco Laboratories, Detroit, MI) was dissolved in sterile physiological saline (0.9% NaCl, w/v).…”

Peroxynitrite Protects Neurons against Nitric Oxide-mediated Apoptosis

“…Hepatocytes are cells prone to hydrogen peroxide (H 2 O 2 )-mediated activation of glucose-6-phosphate dehydrogenase (G6PD), an enzyme that catalyzes the first rate-limiting step in the oxidative branch of the pentose phosphate pathway (PPP) (18,19). Furthermore, stimulation of this pathway in neurons (20) and astrocytes (21) has been proposed to elicit a protective action against H 2 O 2 toxicity through the PPP activity-mediated production of NADPH, a cofactor necessary for GSH regeneration from oxidized glutathione (GSSG) (22,23).…”