Inhibitory Effect of the Intravenous Anesthetic, Ketamine, on Rat Mesangial Cell Proliferation

Jimi, Nobuo; Segawa, Keiko; Minami, Kouichiro; Sata, Takeyoshi; Shigematsu, Akio

doi:10.1213/00000539-199701000-00034

Cited by 23 publications

(11 citation statements)

References 19 publications

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“…[2][3][4] In addition, Jimi et al . 5 demonstrated that ketamine inhibits TNF-α induced [ 3 H]thymidine incorporation into rat mesangial cells, demonstrating that ketamine also inhibits other welldescribed biologic effects of TNF-α. Ketamine reduces the systemic production and release of the proinflammatory cytokine IL-6 during and following cardiopulmonary bypass (CPB).…”

Section: Discussionmentioning

confidence: 94%

“…Ketamine reduces the systemic production and release of the proinflammatory cytokine IL-6 during and following cardiopulmonary bypass (CPB). 6 Since CPB is a clinical condition characterized by systemic endotoxemia, 6 these reports [2][3][4][5][6] demonstrate that ketamine has antiinflammatory activity (reduces the LPSinduced release and/or biological effects of the proinflammatory cytokines). However, the mechanism of suppression by ketamine of the LPS-induced proinflammatory cytokine production and release has not previously been reported.…”

Section: Discussionmentioning

confidence: 99%

“…5 In addition, ketamine attenuates the systemic release of the proinflammatory cytokine IL-6 in humans during and following cardiopulmonary bypass in vivo , 6 a clinical condition characterized by systemic endotoxemia and proinflammatory cytokine production and release. Because NF-6B activation initiates LPS-induced production of TNF-α by inflammatory cells, these reports suggest that ketamine may exert its antiinflammatory effect by inhibiting LPS-induced NF-6B activation.…”

Section: Laboratory Investigationsmentioning

confidence: 99%

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Ketamine suppresses endotoxin-induced NF-κB expression

Sakai

Ichiyama

Whitten

et al. 2000

Can J Anesth/J Can Anesth

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Purpose: Ketamine reduces endotoxin-induced production of proinflammatory cytokines, including tumour necrosis factor-α (TNF), in several types of inflammatory cells, including monocytes and macrophages. Transcription of the genes that encode production of these proinflammatory cytokines is regulated by nuclear factor-kappa B (NF-6B). Cytoplasmic B protein is activated by endotoxin (LPS) as well as by TNF, allowing B protein to migrate into the cell nucleus to activate gene transcription for these inflammatory mediators. Because NF-6B is likely involved in brain injury and inflammatory neurodegenerative disease, such as multiple sclerosis, we examined whether ketamine inhibits LPS-induced activation of NF-6B in human glioma cells in vitro and intact mouse brain cells in vivo. Methods: Endotoxin-induced NF-6B expression in both the human glioma cells in vitro and the intact mouse brain cells in vivo was determined by electrophoretic mobility shift assays (EMSA) of nuclear extracts and measurement of NF-6B expression by densitometry. Endotoxin was injected intracerebroventricularly in vivo and intact brain was harvested. Klenow fragment labeling was used to identify NF-6B protein for both the in vivo and vitro experiments.Results: Endotoxin treatment increased NF-6B expression (P < 0.05) both in vivo and vitro compared with control (untreated) cells. Ketamine suppressed endotoxin-induced neuronal NF-6B activation in a dose-dependent manner (P < 0.05, except for the 10 -5 M concentration in vitro) both in vivo and vitro.Conclusion: Ketamine inhibits endotoxin-induced NF-6B expression in brain cells in vivo and vitro and it is suggested that this may have implications in the neuroprotective effects of ketamine reported by other investigators.Objectif : La kétamine réduit la production de cytokines pro-inflammatoires induite par endotoxine, y compris le facteur nécrosant des tumeurs (TNF), dans certains types de cellules inflammatoires comprenant les monocytes et les macrophages. La transcription des gènes qui encodent la production de ces cytokines pro-inflammatoires est réglée par le facteur-kappa B nucléaire (NF-6B).La protéine cytoplasmique 6B est activée par l'endotoxine (LPS) et par le TNF et peut ainsi migrer dans le noyau cellulaire et activer la transcription génique pour ces médi-ateurs de l'inflammation. Comme le NF-6B participe probablement aux lésions cérébrales et aux maladies inflammatoires neurodégénératives, dont la sclérose en plaques, notre but était de savoir si la kétamine inhibe l'activation de NF-6B induit par LPS dans des cellules de gliome humain in vitro et dans des cellules cérébrales intactes de souris in vivo. Méthode : L'expression du NF-6B induite par endotoxine dans les cellules humaines in vitro et dans les cellules de souris in vivo a été déterminée par une étude de retardement de la mobilité électrophorétique (ERME) d'extraits nucléaires et la mesure de l'expression du NF-6B a été faite par densitométrie. L'endotoxine a été injectée dans les ventricules cérébraux in vivo et du tissu...

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Laboratory Investigationsmentioning

confidence: 99%

See 1 more Smart Citation

Ketamine suppresses endotoxin-induced NF-κB expression

Sakai

Ichiyama

Whitten

et al. 2000

Can J Anesth/J Can Anesth

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“…This is the first report on the effects of continuous infusions of ketamine, propofol, or thiamylal on the decrease in RBF induced by exogenous NA. Our previous reports showed that ketamine increased adenosine 3),5)-cyclic monophosphate levels in cultured mesangial cells of the rat kidney [23]. Recent studies [9] have revealed that adrenomedullin, which also increases the cyclic adenosine monophosphate levels in mesangial cells of rat kidney, inhibits the pressor effects and the decrease in RBF induced by NA in rats.…”

Section: Discussionmentioning

confidence: 93%

Effects of the Intravenously Administered Anaesthetics Ketamine, Propofol, and Thiamylal on the Cortical Renal Blood Flow in Rats

Shiga

Minami²,

Uezono³

et al. 2003

Pharmacology

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Intravenous anaesthetics such as ketamine, propofol, and thiamylal are widely used, although the direct effects of these anaesthetics on the renal blood flow (RBF) have not been well elucidated. In this study, we examined the effects of bolus and continuous administrations of ketamine, propofol, and thiamylal on cortical RBF and the effects of noradrenaline (NA) on RBF under continuous administration of these anaesthetics. We used laser Doppler flowmetry to measure the effects of bolus injection and continuous infusion of ketamine, propofol, and thiamylal on cortical RBF in male Wistar rats. We also examined the effects of the anaesthetics on mean arterial blood pressure (MAP) and heart rate (HR). Bolus injections of ketamine, propofol, or thiamylal (1–8 mg/kg each, n = 10) at clinically relevant concentrations did not affect MAP, HR, or RBF. Continuous administration of ketamine, propofol, or thiamylal (1–8 mg/kg/h each, n = 10) did not affect MAP, HR or RBF. Exogenous NA (2 µg/kg) caused an increase in MAP and a decrease in RBF and HR. In experiments with continuous infusions of propofol or thiamylal (1–8 mg/kg/h each, n = 10), similar results were observed without infusion of any anaesthetics. However, bolus injection of NA did not result in a decrease in RBF during continuous ketamine infusion (98.8 ± 6.7% of control, n = 6, p < 0.05), while ketamine did not affect the NA-induced increase in MAP. In conclusion, bolus and continuous administrations of ketamine, propofol, and thiamylal did not affect the RBF. From our present findings, ketamine would be useful for maintaining the RBF.

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“…Segawa et al [12] reported that adrenomedullin, a hypotensive peptide originally isolated from human pheochromocytoma, increases intracellular cAMP levels in MCs. Moreover, an intravenous anesthetic, ketamine, inhibits MC proliferation via increased intracellu-Ogata/Minami/Segawa/Yamamoto/Kim/ Shigematsu lar cAMP levels [13]. These results suggest that cAMP inhibits MC proliferation.…”

Section: Introductionmentioning

confidence: 85%

A Forskolin Derivative, Colforsin Daropate Hydrochloride, Inhibits Rat Mesangial Cell Mitogenesis via the Cyclic AMP Pathway

Ogata

Minami²,

Segawa³

et al. 2003

Pharmacology

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A forskolin derivative, colforsin daropate hydrochloride (CDH), has been introduced as an inotropic agent that acts directly on adenylate cyclase to increase intracellular cyclic AMP (cAMP) levels and ventricular contractility, resulting in positive inotropic activity. We investigated the effects of CDH on rat mesangial cell (MC) proliferation. CDH (10^–7–10^–5 mol/l) inhibited [³H]thymidine incorporation into cultured rat MCs in a concentration-dependent manner. CDH (10^–7–10^–5 mol/l) also decreased cell numbers in a similar manner, and stimulated cAMP accumulation in MCs in a concentration-dependent manner. A protein kinase A inhibitor, H-89, abolished the inhibitory effects of CDH on MC mitogenesis. These findings suggest that CDH would inhibit the proliferation of rat MCs via the cAMP pathway.

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Inhibitory Effect of the Intravenous Anesthetic, Ketamine, on Rat Mesangial Cell Proliferation

Cited by 23 publications

References 19 publications

Ketamine suppresses endotoxin-induced NF-κB expression

Ketamine suppresses endotoxin-induced NF-κB expression

Effects of the Intravenously Administered Anaesthetics Ketamine, Propofol, and Thiamylal on the Cortical Renal Blood Flow in Rats

A Forskolin Derivative, Colforsin Daropate Hydrochloride, Inhibits Rat Mesangial Cell Mitogenesis via the Cyclic AMP Pathway

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