Formation of activated oxygen in the hypoxic rat liver

Abstract

The biliary GSSG efflux rate of normoxic perfused rat liver was 1.5 +/- 0.2 nmol/min/g liver wet weight. The GSSG efflux rate as indicator for the flux through the glutathione peroxidase reaction and, therefore, for an oxidative loading increased with the extent of hypoxia. 2.6 +/- 0.5 nmol/min/g were released from the severely hypoxic liver. The hydroxyl radical scavenger formate as well as the xanthine oxidase inhibitor allopurinol reduced the efflux rate of GSSG. GSH was released from the perfused liver at a rate of 15.5 nmol/min/g which was nearly unchanged in severe hypoxia. The high rate of glucose liberation from the hypoxic liver declined to almost that of the normoxic organ in the presence of formate. There is an 'oxidative stress' during hypoxic liver perfusion which probably originates from increased generation of activated oxygen species in the degradation of purine nucleotides.

Hypoxic suppression ofE. coli-induced NF-κB and AP-1 transactivation by oxyradical signaling

“…Xanthine oxidase-derived oxyradicals are abundantly generated during severe H/R stress of the liver without microbial exposure (14,28). Hepatic oxyradical generation likewise follows gramnegative bacterial stimulation without preceding hypoxic stress (4,33).…”

“…Common to hypoxic stress of mammalian cells or their stimulation by gram-negative microbial products is the de novo generation of oxyradicals from mitochondrial and xanthine oxidase-derived origins (4,6,14,28). Oxyradical-mediated signaling activates canonical oxidation-reduction (redox)-sensitive transcription factors, such as the NF-B/c-Rel and activator protein (AP)-1 families of DNA-binding proteins, followed by their nuclear localization and binding to specific cis-acting motifs in the promoter regions of inflammatory cytokine genes (5,15,30).…”

“…Oxyradical-mediated signaling activates canonical oxidation-reduction (redox)-sensitive transcription factors, such as the NF-B/c-Rel and activator protein (AP)-1 families of DNA-binding proteins, followed by their nuclear localization and binding to specific cis-acting motifs in the promoter regions of inflammatory cytokine genes (5,15,30). Oxyradical generation and signaling in the intact liver are well documented after experimental perturbations in the hepatic O 2 supply, resulting in hypoxic stress (14,28), or challenge by gram-negative stimuli (4,33). Consequently, it has been assumed, but not proven, that combined or sequential hypoxic stress of the liver and intraportal bacteremia additively promote oxyradical-mediated transactivation of NF-B and AP-1 complexes.…”

Oxygenogenesis, a Defence Mechanism of the Newt for Surviving Anoxic Stress~!2008-11-11~!2009-01-14~!2009-03-13~!

“…The biochemical origin of the molecular oxygen released in the anoxic newts' blood is a very complex problem, but if we consider that the elements in play are only lack of oxygen, hepatic parenchyma, and products of haemolytic crisis, we can individuate several clews. Hypoxia is known to induce, especially in the liver, the production of free radicals, the so-called ROS, reactive oxygen species [45][46][47][48][49][50], but the hepatocytes possess enzymes which neutralise the ROS just by producing molecular oxygen [51,52] -essentially superoxide dismutase (SOD) and catalase. The Fe 2+ released in large amounts during the haemolytic process and destined to oxidise into Fe 3+ outside the cells [53] should be linked with this process as an electron donor.…”

Dynamics of Hepatic Melanogenesis in Newts in Recovery Phase from Hypoxia~!2008-11-17~!2008-12-01~!2009-01-26~!

“…From abundant literature it appears that in hypoxia several organs, especially the liver, produce superoxides [42][43][44][45][46][47]; thanks to catalysis by Fe 2+ of haemolytic origin, molecular oxygen can be continuously generated from the superoxides through the Haber-Weiss cycle [48,49] -and we have been able to demonstrate that indeed in newts under anoxia haemolysis and oxygenogenesis occur simultaneously [1]. When, after respiratory crisis, an animal return to normoxia, and thus normal oxygen levels from the external environment return to the blood circulation, the equilibrium of the reaction of endogenous production of the molecule shifts to the left, and the superoxides are no longer utilised within the system and neutralised; it follows that they attack the DNA in the cells where oxygenogenesis is taking place and kill them [28].…”