Reperfusion induces 5-lipoxygenase translocation and leukotriene C4 production in ischemic brain

1995 ◽  
Vol 268 (3) ◽  
pp. H1249-H1257 ◽  
Author(s):  
T. Ohtsuki ◽  
M. Matsumoto ◽  
Y. Hayashi ◽  
K. Yamamoto ◽  
K. Kitagawa ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Oxygen Radicals ◽  
Oxygen Radical ◽  
Leukotriene C4 ◽  
Radical Scavengers ◽  
Membrane Phospholipids ◽  
Neuronal Necrosis ◽  
Ischemic Brain ◽  
External Stimulation ◽  
C4 Production

5-Lipoxygenase (5-LO) converts arachidonic acid, released from membrane phospholipids upon external stimulation, to leukotriene C4 (LTC4), which induces various kinds of cellular and molecular responses. We examined the effects of 5 min of ischemia on brain 5-LO and LTC4 during reperfusion using the gerbil model of transient forebrain ischemia that develops neuronal necrosis selectively in the hippocampus. Neurons exhibited dense 5-LO immunoreactivity; 5-LO was partially redistributed from cytosolic to particulate fractions 3 min during reperfusion. LTC4 was generated in neurons and was increased in all forebrain regions during reperfusion. Postischemic increases in LTC4 were inhomogeneous; a greater increase was observed in the hippocampus (13.37 +/- 0.24 pmol/g tissue) than in the other regions (cerebral cortex: 3.29 +/- 1.09 pmol/g). Superoxide dismutase and dimethylthiourea, oxygen radical scavengers, attenuated the production of LTC4 and damage to the neurons in the hippocampus during reperfusion. Our findings indicated that reperfusion, which was associated with translocation of cytosolic 5-LO to membranes and generation of oxygen radicals, induced the production of LTC4 and suggested that excess LTC4 production may mediate irreversible reperfusion injuries in the hippocampal neurons.

scholarly journals Oxygen Radicals Do Not Play a Role in Arteriolar Dilation during Cortical Spreading Depression

1996 ◽  
Vol 16 (1) ◽  
pp. 175-179 ◽  
Author(s):  
Wei Meng ◽  
David W. Busija
Keyword(s):  
Superoxide Dismutase ◽  
Cortical Spreading Depression ◽  
Oxygen Radicals ◽  
Spreading Depression ◽  
Oxygen Radical ◽  
Onset Latency ◽  
Radical Scavengers ◽  
Cranial Window ◽  
Cerebral Arterioles

This study examined the role of oxygen radicals in pial arteriolar changes during cortical spreading depression (CSD). CSD was induced by microinjection of 5% KCl in anesthetized adult rabbits. Pial diameter was measured with a closed cranial window and intravital microscopy. During control CSD (n = 12), the dilation amplitude and area were 55 ± 14% and 693 ± 69 mm2 (baseline = 76 ± 14 μm), respectively. Oxygen radical scavengers, superoxide dismutase (SOD; 105 U/ml, topical application; n = 5) or oxypurinol (50 mg/kg i.v.; n = 7), did not alter the dilation amplitude and area or change onset latency during CSD. Further, SOD and oxypurinol did not prevent NG-nitro-L-arginine from attenuating arteriolar dilation during CSD (n = 12). We conclude that oxygen radicals do not play a role in the transient dilation of cerebral arterioles during CSD.

Tumour Necrosis Factor-α and Endotoxin Induce Less Prostaglandin E2 Production from Hypothalami of Rats Fed Coconut Oil than from Hypothalami of Rats Fed Maize Oil

1990 ◽  
Vol 79 (6) ◽  
pp. 657-662 ◽  
Author(s):  
David C. Bibby ◽  
Robert F. Grimble
Keyword(s):  
Prostaglandin E2 ◽  
Tumour Necrosis Factor ◽  
Tumour Necrosis ◽  
Coconut Oil ◽  
Leukotriene C4 ◽  
Tumour Necrosis Factor Α ◽  
Factor Α ◽  
C4 Production ◽  
Necrosis Factor ◽  
Maize Oil

1. The primary aim of the study was to determine whether the stimulatory effect of tumour necrosis factor-α and endotoxin on hypothalamic prostaglandin E2 production was influenced by dietary fats containing different amounts of linoleic acid. Rats received diets containing 20% (w/w) maize oil or 19% (w/w) coconut oil plus 1% (w/w) maize oil for 8 weeks. 2. A subsidiary part of the study examined the effect of tumour necrosis factor-α on the ability of the calcium ionophore A23187 to stimulate prostaglandin E2 and leukotriene C4 production by hypothalami from chow-fed rats. 3. While tumour necrosis factor-α enhanced prostaglandin E2 production in response to A23187, neither agent had an effect on leukotriene C4 production. 4. Hypothalami from rats fed maize oil exhibited increased prostaglandin E2 production in response to both pyrogens. This did not occur with hypothalami from rats fed coconut oil. 5. Coconut oil might exert its modulatory effect by bringing about a reduction in membrane phospholipid arachidonic acid content.

Oxygen radical mechanisms of brain injury following ischemia and reperfusion

1991 ◽  
Vol 71 (4) ◽  
pp. 1185-1195 ◽  
Author(s):  
R. J. Traystman ◽  
J. R. Kirsch ◽  
R. C. Koehler
Keyword(s):  
Fatty Acids ◽  
Brain Injury ◽  
Free Fatty Acids ◽  
Blood Brain Barrier ◽  
Adenine Nucleotides ◽  
Oxygen Radical ◽  
Brain Barrier ◽  
Ischemia And Reperfusion ◽  
Radical Scavengers ◽  
Blood Brain

This review addresses current understanding of oxygen radical mechanisms as they relate to the brain during ischemia and reperfusion. The mechanism for radical production remains speculative in large part because of the difficulty of measuring radical species in vivo. Breakdown of lipid membranes during ischemia leads to accumulation of free fatty acids. Decreased energy stores during ischemia result in the accumulation of adenine nucleotides. During reperfusion, metabolism of free fatty acids via the cyclooxygenase pathway and metabolism of adenine nucleotides via the xanthine oxidase pathway are the most likely sources of oxygen radicals. Although leukocytes have been found to accumulate in some models of ischemia and reperfusion, their mechanistic role remains in question. Therapeutic strategies aimed at decreasing brain injury have included administration of radical scavengers at the time of reperfusion. Efficacy of traditional oxygen radical scavengers such as superoxide dismutase and catalase may be limited by their inability to cross the blood-brain barrier. Lipid-soluble antioxidants appear more efficacious because of their ability to cross the blood-brain barrier and because of their presence in membrane structures where peroxidative reactions can be halted.

Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation

1988 ◽  
Vol 254 (5) ◽  
pp. G768-G774 ◽  
Author(s):  
D. A. Parks ◽  
T. K. Williams ◽  
J. S. Beckman
Keyword(s):  
Small Intestine ◽  
Oxygen Radicals ◽  
Total Activity ◽  
Xanthine Dehydrogenase ◽  
Oxygen Radical ◽  
Morphological Evidence ◽  
Cellular Injury ◽  
Rat Intestine ◽  
Entire Small Intestine ◽  
Ischemic Intestine

Oxygen radicals derived from xanthine oxidase (XO) are important mediators of the cellular injury associated with reperfusion of ischemic intestine, stomach, liver, kidney, and pancreas. XO exists in nonischemic tissue predominantly as xanthine dehydrogenase (XDH) and converts to oxygen radical-producing XO with ischemia. Grinding intestine under liquid nitrogen and placing the powder in phosphate buffer (pH 7.0) containing thiol reductants and protease inhibitors adequately preserved total XDH + XO activity and the percentage in the oxidase form (%XO) for 24 h. Total activity in nonischemic intestine ranged from 374 nmol.min-1.g-1 in duodenum to 138 nmol.min-1.g-1 in ileum, while XO activity was approximately 19% of total activity throughout the entire small intestine. The rate of XDH conversion to XO during normothermic ischemia varied only slightly throughout the intestine, increasing 13% per hour to 34, 46, and 61% XO after 1, 2, and 3 h of ischemia, respectively. Our results contrast with previous reports where XDH conversion to XO occurred within 60 s ischemia but are consistent with physiological and morphological evidence of ischemic injury and provide further support for involvement of XO in intestinal injury associated with ischemia.

Clinical Indications for the Administration of Oxygen Radical Scavengers

1993 ◽  
pp. 1271-1277
Author(s):  
J. Hill ◽  
T. Lindsay ◽  
C. R. Valeri ◽  
D. Shepro ◽  
H. B. Hechtman
Keyword(s):  
Oxygen Radical ◽  
Radical Scavengers ◽  
Clinical Indications

Reactivity of Oxygen Radicals [HO•, RO•, HOO•, ROO-, and RC(O)O•]

1992 ◽  
Author(s):  
Donald T. Sawyer ◽  
R. J. P. Williams
Keyword(s):  
Oxygen Atom ◽  
Hydroxyl Radical ◽  
Gas Phase ◽  
Oxygen Radicals ◽  
Oxygen Radical ◽  
Superoxide Ion ◽  
Radical Reactivity ◽  
The Family ◽  
Hydrocarbon Substrates

Oxygen radicals are defined as those molecules that contain an oxygen atom with an unpaired, nonbonding electron (e.g., HO·). Although triplet dioxygen (·O2·) and superoxide ion (O2 - ·) come under this definition, their nonradical chemistry dominates their reactivity, which is discussed in Chapters 6 (·O2·) and 7 (O2-·). The hydroxyl radical (HO·) is the most reactive member of the family of oxygen radicals [HO·, RO·, ·O·, HOO·, ROO·, and RC(O)O·], and is the focus of most oxygen radical research. In the gas phase the dramatic example of oxygen radical reactivity with hydrocarbon substrates is combustion, which is initiated by HO· (or RO· or MO·) and propagated by ·O2· and ·O·.

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