Role of prostaglandin endoperoxide PGG2 in inflammatory processes

Kuehl, Frederick A.; Humes, John L.; Egan, Robert W.; Ham, Edward A.; Beveridge, G. C.; Arman, C. G. Van

doi:10.1038/265170a0

Cited by 308 publications

(73 citation statements)

References 21 publications

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“…ROS, including hydroxy radical, hydrogen peroxide, and hydrogen peroxide, are demonstrated to be one of the major factors in reperfusion injury. 16,17) The main productive sources of free radicals in I/R are suggested to be involved in the xanthine oxidase-hypoxanthine system, 18) the electron transmission system in mitochondria, the arachidonic cascade, 19) and the NADPH oxidase system in leukocytes. 20) The increased ROS contribute to various consequences responsible for I/R injury, such as modification of phospholipids and proteins leading to lipid peroxidation and oxidation of thiol groups.…”

Section: Discussionmentioning

confidence: 99%

MCI-186 (3-Methyl-1-phenyl-2-pyrazolin-5-one) Attenuated Simulated Ischemia/Reperfusion Injury in Cultured Rat Hippocampal Cells

Xin-sheng

Wang

et al. 2006

Biological & Pharmaceutical Bulletin

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The reactive oxygen species and Ca 2؉ overload play a critical role in ischemia/reperfusion (I/R) injury. MCI-186 has potent effects in the brain as a free radical scavenger in ischemia-reperfusion. Acute glucose-oxygen deprivation and subsequent reoxygenation were used to model ischemia/reperfusion injury in cultured hippocampal cells. MCI-186 reduced malondialdehyde level and raised the SOD activity when applied upon reoxygenation in a dose-dependent manner compared with the untreated group. The peak neuroprotective effects occurred at 100 and 300 m mM. Intracellular free calcium concentration ([Ca 2؉ ] i ) was significantly reduced in the 100 m mM MCI-186-treated group compared to the untreated group (32.5؎4.0 versus 50.2؎3.6, pϽ0.01). Treatment with 100 m mM MCI-186 significantly inhibited the decrease of mitochondria membrane potential after simulated ischemia/ reperfusion (204؎11.6% compared with the untreated group, pϽ0.01). Cell apoptotic rate was significantly decreased following MCI-186 treatment from 33.7؎2.3% (untreated group) to 16.6؎1.4% (100 m mM MCI-186 treated group). There was no significantly protective difference between 100 and 300 m mM MCI-186. MCI-186 effectively protects neuron injury after simulated ischemia/reperfusion by inhibiting lipid peroxidation, reducing Ca 2؉ overload, elevating mitochondria membrane potential, and decreasing apoptosis.

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Section: Discussionmentioning

confidence: 99%

MCI-186 (3-Methyl-1-phenyl-2-pyrazolin-5-one) Attenuated Simulated Ischemia/Reperfusion Injury in Cultured Rat Hippocampal Cells

Xin-sheng

Wang

et al. 2006

Biological & Pharmaceutical Bulletin

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“…Anti-oxidants such as ascorbic acid and propylgallate enhance 6-oxo-PGF1,1 formation from radiolabelled arachidonic acid and PGH2 in ram seminal vesicle microsomes (Beetens, Claeys & Herman, 1981). Likewise, the phenolic compound MK 447 and its analogues enhance PGE2 formation by bovine seminal vesicle microsomes (Kuehl, Humes, Egan, Ham, Beveridge & Van Arman, 1977;Payne, Dewald, Siegl, Gubler, Ott & Baggiolini, 1982) probably by scavenging the enzymeinactivating oxidative radicals produced in prostaglandin biosynthesis. Whether such mechanisms could contribute to the actions of BW755C awaits further study.…”

Section: Discussionmentioning

confidence: 99%

Stimulation and inhibition of prostacyclin formation in the gastric mucosa and ileum in vitro by anti‐inflammatory agents

Boughton‐Smith

Whittle

1983

British J Pharmacology

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Homogenates of rat gastric mucosa, forestomach and ileum and dog gastric mucosa reproducibly generated prostacyclin from endogenous substrate. Prostacyclin formation was inhibited by pre‐incubation with indomethacin, flurbiprofen, naproxen, ketoprofen or meclofenamate (0.1–10 μm). BW755C (3‐amino‐1[m‐(trifluoromethyl)‐phenyl]‐2‐pyrazoline) stimulated prostacyclin production in the rat gastric mucosa and ileum with inhibition occurring only at high concentrations (>200 μm). The stimulation of prostacyclin production by BW755C in rat forestomach homogenates was less pronounced, with inhibition at concentrations > 20 μm. BW755C thus exhibits differential activity on prostacyclin production from different gastric tissues in vitro. The antioxidant‐lipoxygenase inhibitor, nordihydroguiaretic acid (NDGA, 3–15 μm) likewise augmented rat mucosal prostacyclin formation. Paracetamol stimulated and, at higher concentrations, inhibited prostacyclin formation (> 1 mm), and had comparable activity in both rat gastric tissues. The ability of NDGA and BW755C to enhance prostacyclin generation may reflect the removal of a modulating influence of lipoxygenase products on prostacyclin formation, the diversion of substrate to the cyclo‐oxygenase pathway, or free‐radical scavenging.

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“…The inner medulla was separated by careful dissection, sliced with a Stadie-Riggs microtome and pooled for each experiment. Slices (30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40) mg) were first incubated for 40 min in 3 ml of Krebs-Henseleit buffer containing 1 mg/ml glucose. After washing with prewarmed medium, slices were transferred to flasks containing 2 ml of fresh medium for the final 30 min.…”

Section: Prostaglandinsmentioning

confidence: 99%

Different mode of action between norepinephrine and phenylephrine on prostaglandin synthesis by dog renal inner medullary slices.

1983

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Abstract-The dog renal inner medullary slices synthesized and released prostaglandin (PG) E2, PGF21, PGI2 (measured as 6-keto-PGF,.) and thromboxane (TX) A2 (measured as TXB2). When incubated in the presence of norepinephrine, the synthesis of these arachidonic acid metabolites were stimulated about 2-fold. The norepinephrine effect could be antagonized by the addition of an a-adrenoceptor blocking agent, phenoxy benzamine, but not by a Q-adrenoceptor blocking drug, propranolol. Phenoxybenzamine at concentrations that block norepinephrine stimulation of prostaglandin biosynthesis did not suppress the increase in prostaglandins synthesized by exogenous arachidonic acid. By contrast, phenylephrine caused only PGI2 production without producing other prostaglandins and thromboxane. This phenylephrine effect could not be antagonized by either a or 8-adrenoceptor blocking agents, but it was abolished by the specific PGI2 synthetase inhibitors 15-hydroperoxy arachidonic acid and tranylcypromine. These results suggest that norepinephrine-induced prostaglandin synthesis is mediated via an a-adrenergic receptor mechanism, whereas phenylephrine stimulation is primarily occurring at the step which follows the cyclooxygenase reaction in the metabolism of arachidonic acid.

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Role of prostaglandin endoperoxide PGG2 in inflammatory processes

Cited by 308 publications

References 21 publications

MCI-186 (3-Methyl-1-phenyl-2-pyrazolin-5-one) Attenuated Simulated Ischemia/Reperfusion Injury in Cultured Rat Hippocampal Cells

MCI-186 (3-Methyl-1-phenyl-2-pyrazolin-5-one) Attenuated Simulated Ischemia/Reperfusion Injury in Cultured Rat Hippocampal Cells

Stimulation and inhibition of prostacyclin formation in the gastric mucosa and ileum in vitro by anti‐inflammatory agents

Different mode of action between norepinephrine and phenylephrine on prostaglandin synthesis by dog renal inner medullary slices.

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