Diphenhydramine reduces endotoxin effects on lung vascular permeability in sheep

Brigham, Kenneth L.; Padove, S. J.; Bryant, DJ; McKeen, Charles R.; Bowers, Ronald E.

doi:10.1152/jappl.1980.49.3.516

Cited by 18 publications

(8 citation statements)

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“…A contributory role for histamine and NO in increased pulmonary vascular permeation during septic shock has been documented (10,34,40). In this study, we found that treatment with diphenhydramine or L-NNA significantly but partially inhibited endotoxin-induced lung vascular permeability.…”

Section: Discussionsupporting

confidence: 56%

“…Moreover, we have found that endotoxin administration causes superinduction of histamine H 1 receptors in cardiovascular tissues of rabbits (20,21). Earlier studies showed that blockade of histamine H 1 receptors with diphenhydramine was effective in the increase in lung vascular permeability in animal models of sepsis (10,34). Thus the hypothesis that histamine may, at least in part, mediate increased lung vascular permeability caused by endotoxemia is plausible.…”

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confidence: 80%

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Therapeutic effect of in vivo transfection of transcription factor decoy to NF-κB on septic lung in mice

Matsuda

Hattori²,

Takahashi³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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Nuclear factor-kappaB (NF-kappaB) plays a key role in regulating expression of several genes involved in the pathophysiology of endotoxic shock. We investigated whether in vivo introduction of synthetic double-stranded DNA with high affinity for the NF-kappaB binding site could block expression of genes mediating pulmonary vascular permeation and thereby provide effective therapy for septic lung failure. Endotoxic shock was induced by an intravenous injection of 10 mg/kg Escherichia coli endotoxin in mice. We introduced NF-kappaB decoy oligodeoxynucleotide (ODN) in vivo 1 h after endotoxic shock by using a gene transfer kit. At 10 h, blood samples were collected for measurement of histamine and for blood-gas analysis. Gene and protein expression levels of target molecules were determined by means of Northern and Western blot analyses, respectively. The transpulmonary flux of (125)I-labeled albumin was used as an index of lung vascular permeability. Administration of endotoxin caused marked increases in plasma histamine and gene and protein expressions of histidine decarboxylase, histamine H(1) receptors, and inducible nitric oxide synthase in lung tissues. Elevated lung vascular permeability was also found. Blood-gas analysis showed concurrent decreases in arterial Po(2), Pco(2), and pH. All of these events induced by endotoxin were significantly inhibited by transfection of NF-kappaB decoy ODN but not by its mutated (scrambled) form (used as a control). Our results indicate for the first time the potential usefulness of NF-kappaB decoy ODN for gene therapy of endotoxic shock.

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Section: Discussionsupporting

confidence: 56%

mentioning

confidence: 80%

Therapeutic effect of in vivo transfection of transcription factor decoy to NF-κB on septic lung in mice

Matsuda

Hattori²,

Takahashi³

et al. 2004

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…This suggests that, while both H 1 - and H 2 -receptors are involved in lung and liver injury, only H 2 -receptors contribute to kidney injury in sepsis. The involvement of histamine via H 1 -receptors in lung vascular hyperpermeability in sepsis has been documented [9, 31]. H 2 -receptors have also been shown to be involved in the recruitment of neutrophils and protein leaks in LPS-induced acute lung injury [32].…”

Section: Discussionmentioning

confidence: 99%

Critical role of endogenous histamine in promoting end-organ tissue injury in sepsis

Hattori

Yamazaki

Ohashi

et al. 2016

ICMx

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BackgroundHistamine assumes an important role as a major mediator in various pathologic disorders associated with inflammation and immune reactions. However, the involvement of histamine in the pathological conditions and symptoms of sepsis remains entirely unknown. In this study, we establish that histamine is identified as a contributory mediator to promoting the development of organ injury in sepsis.MethodsHistidine decarboxylase (HDC) gene knockout (HDC−/−) mice, histamine H1-/H2-receptor gene-double knockout (H1R−/−/H2R−/−) mice, and their littermate wild-type (WT) C57BL/6J mice underwent cecal ligation and puncture (CLP) or sham operation. Some WT mice were injected intraperitoneally with d-chlorpheniramine and famotidine 60 min before CLP to block H1- and H2-receptors, respectively.ResultsIn mice rendered septic by CLP, tissue histamine levels were elevated in association with increased HDC expression. Sepsis-induced abnormal cytokine production and multiple organ injury (lung, liver, and kidney) were significantly less pronounced in HDC−/− mice as compared with WT controls, and HDC deficiency had improved survival in sepsis. This benefit corresponded with a significant reduction in activation levels of the nuclear factor (NF)-κB signaling pathway. H1R−/−/H2R−/− mice apparently behaved similar to HDC knockout mice in reducing sepsis-related pathological changes. Pharmacological interventions with H1- and H2-receptor antagonists indicated that both H1- and H2-receptors were involved in septic lung and liver injury, whereas only H2-receptors contributed to septic kidney injury.ConclusionsIn the setting of sepsis, histamine, through activation of H1- and H2-receptors, serves as an aggravating mediator to contribute to the development of sepsis-driven major end-organ failure.Electronic supplementary materialThe online version of this article (doi:10.1186/s40635-016-0109-y) contains supplementary material, which is available to authorized users.

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“…In agreement with this, the current study showed a significant increase in H 1 -receptor mRNA in lungs from CLP-induced septic mice. Histamine can affect pulmonary vascular response, lung mechanics, and pulmonary vascular permeability, effects that may be blocked by H 1 -receptor antagonism (Brigham et al, 1980). Thus, histamine may be a potentially important mediator in the pathogenesis of septic lung injury.…”

Section: Discussionmentioning

confidence: 99%

Nuclear Factor-κB Decoy Oligodeoxynucleotides Prevent Acute Lung Injury in Mice with Cecal Ligation and Puncture-Induced Sepsis

Matsuda

Hattori²,

Jesmin³

et al. 2004

Mol Pharmacol

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The transcription factor nuclear factor-B (NF-B) plays a key role in expression of many inflammatory genes responsible for the pathophysiology of sepsis-induced acute lung injury. We investigated whether the introduction of synthetic doublestranded oligodeoxynucleotides (ODNs) with consensus NF-B sequence as transcription factor decoy can prevent acute lung injury with suppression of pulmonary expression of multiple genes involved in its pathological process in a cecal ligation and puncture septic mouse model. NF-B decoy ODNs were introduced with the aid of the hemagglutinating virus of Japanenvelope vector method. Northern blot analysis indicated that transfection of NF-B decoy ODN, but not of its scrambled form, resulted in a significant inhibition of sepsis-induced gene overexpression of inducible nitric-oxide synthase (iNOS), cyclooxygenase-2, histamine H 1 -receptor, platelet-activating factor receptor, and bradykinin B 1 and B 2 receptors in lung tissues. Histological damage in lungs (wall thickening, inflammatory infiltrate, and hemorrhage), increased pulmonary vascular permeability, and blood gas exchange impairment were clearly documented in mice after cecal ligation and puncture. These changes were strongly eliminated by the introduction of NF-B decoy but not of scrambled ODN. The effects of the iNOS inhibitor FR260330 on these histological and functional derangements compared unfavorably with those of NF-B decoy ODN transfection. Our results suggest that ODN decoy, acting as in vivo competitor for the transcription factor's ability to bind to cognate recognition sequence, may represent an effective strategy in the treatment of septic acute lung injury.

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Diphenhydramine reduces endotoxin effects on lung vascular permeability in sheep

Cited by 18 publications

References 0 publications

Therapeutic effect of in vivo transfection of transcription factor decoy to NF-κB on septic lung in mice

Therapeutic effect of in vivo transfection of transcription factor decoy to NF-κB on septic lung in mice

Critical role of endogenous histamine in promoting end-organ tissue injury in sepsis

Nuclear Factor-κB Decoy Oligodeoxynucleotides Prevent Acute Lung Injury in Mice with Cecal Ligation and Puncture-Induced Sepsis

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