Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

Irie, Koichiro; Fujii, Emiko; Ishida, Hiroyasu; Wada, Keiji; Suganuma, Taiyo; Nishikori, Tomohiro; Yoshioka, Toshimasa; Muraki, Takamura

doi:10.1038/sj.bjp.0704073

Cited by 48 publications

(34 citation statements)

References 22 publications

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“…These authors provided evidence that tadalafil therapy decreased the levels of circulating inflammatory cytokines in the studied animals (Varma et al, 2012). In accordance with the current findings, another study demonstrated that pretreatment with PDE5I, zaprinast, inhibited the increase in serum TNF-a level in mice (Iric et al 2001). Similarly, Sildenafil, a prototype of PDE5I has shown good effects in experimental colitis by balancing oxidant-antioxidant status and inhibiting ROM production and release of cytokines (Salari-Sharif and Abdollahi, 2010).…”

Section: Discussionsupporting

confidence: 76%

Evaluation of the colo-protective effects of tadalafil in an experimental model of ulcerative colitis in rats

Labib¹,

Abdelzaher²,

Shaker³

et al. 2017

Afr. J. Pharm. Pharmacol.

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Ulcerative colitis is a serious premalignant condition with a confusing multifactorial pathogenesis. It should warrant all attention by researchers, for exploration of new prophylactic or therapeutic drugs targeting its pathophysiology. The current study was conducted to study the possible role of tadalafil and its potential actions in ulcerative colitis rat model, induced by acetic acid. Forty eight male Wistar albino rats were classified into 6 groups: control group, acetic acid (AA)-ulcerated group, AA-ulcerated + tadalafil (1 mg/kg/day), AA-ulcerated + tadalafil (5 mg/kg/day), AA-ulcerated + tadalafil (10 mg/kg/day) and AA-ulcerated + sulfasalazine 100 mg/kg/day groups. Tissue malondialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) were determined. Also, caspase-3 gene expression was measured as an indicator of apoptosis. Histopathological examination of the colonic tissue was also done. In addition, serum levels of interleukin (IL)-1β and tumour necrosis factor (TNF)-α were measured. In AA-ulcerated group, there was significant elevation in tissue MDA levels and MPO activity with upregulation of caspase 3 gene expression. Meanwhile, AA caused decreases in the SOD activities. Also, AA induced elevation in the serum IL-1β and TNF-α levels. Pretreatment with tadalafil in doses of 1, 5 and 10 mg/kg/days guarded against changes in these parameters. Its effects were dose-dependent. According to the results, pretreatment with tadalafil in doses of 1, 5 and 10 mg/kg/day exerted dosedependent beneficial effects against AA-induced damage of the colon, possibly by exerting antiinflammatory and antioxidant effects. Also, reduction of apoptosis proved to be one of the contributing protective mechanisms of actions.

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Section: Discussionsupporting

confidence: 76%

Evaluation of the colo-protective effects of tadalafil in an experimental model of ulcerative colitis in rats

Labib¹,

Abdelzaher²,

Shaker³

et al. 2017

Afr. J. Pharm. Pharmacol.

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“…LPS has previously been shown to increase microvascular permeability. 27 We demonstrated that LPS increased the permeability of lung vasculature in keeping with the normal physiologic response to an inflammatory stimulus. 28 However, increased vascular permeability facilitates metastasis.…”

Section: Discussionmentioning

confidence: 60%

Lipopolysaccharide‐induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion

Harmey

Bucana

Wang

et al. 2002

Intl Journal of Cancer

238

202

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Endotoxin/lipopolysaccharide (LPS), a cell wall component of Gram-negative bacteria, is a potent inflammatory stimulus. We previously reported that LPS increased the growth of experimental metastases in a murine tumor model. Here, we examined the effect of LPS exposure on key determinants of metastasis-angiogenesis, tumor cell invasion, vascular permeability, nitric oxide synthase (NOS) and matrix metalloproteinase 2 (MMP2) expression. BALB/c mice bearing 4T1 lung metastases were given an intraperitoneal (i.p.) injection of 10 g LPS or saline. LPS exposure resulted in increased lung weight and incidence of pleural lesions. LPS increased angiogenesis both in vivo and in vitro. Most cancer patients ultimately succumb to metastatic disease, and up to 50% of cancer patients already have metastatic deposits at the time of diagnosis. 1 In many cases, the primary tumor can be successfully treated by surgery, radiotherapy, chemotherapy or a combination but the subsequent growth of previously dormant or clinically undetectable metastatic deposits presents a serious obstacle to the complete eradication of the disease. Elucidating factors that influence the development and progression of metastatic disease is critical to the development of effective therapies for patients with metastatic deposits.Metastatic tumor growth involves a complex series of sequential events involving a number of cell types, cytokines and pathways. After the initial transformation event, growth of a primary tumor is accompanied by extensive angiogenesis. Cells with a metastatic phenotype invade the tissue stroma and penetrate the blood vessels to enter the circulation. The majority of tumor cells entering the circulation are rapidly destroyed but those that do survive can then become trapped in organ capillary beds and extravasate into the organ parenchyma. Cell proliferation and vascularization of the secondary deposit completes the metastatic process. 2 Endotoxin/lipopolysccharide (LPS), a cell wall constituent of Gram-negative bacteria, is released during growth or lysis of bacteria and acts as a potent inflammatory stimulus, eliciting a range of cytokines, growth factors and inflammatory mediators. LPS and some bacteria have been shown to have angiogenic activity. [3][4][5] Inflammation has been linked with angiogenesis, resulting in changes in permeability, activation of endothelium and vessel remodeling. 6 In support of a link between inflammation and tumor progression, there is a growing body of evidence that anti-inflammatory agents such as the nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclo-oxygenase activity, inhibit both tumorigenesis and growth of colon and mammary tumors. 7 Endotoxin is ubiquitously present in air, and we previously implicated endotoxin in surgically induced tumor growth. 8,9 Endogenous gut bacteria are a major source of endotoxin, which can translocate across the gut into the circulation following surgical trauma or thermal injury. 10 -12 Vascular endothelial growth factor (VEGF), also known as va...

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“…Changes in permeability of microvessels of the skin were monitored by extravasation of intracardial administered Evans blue dye (13,47). Briefly, anesthetized animals were injected into the left atrium with 30 mg/kg body weight of Evans blue dissolved in 0.9% saline.…”

Section: Quantification Of Plasma Leakage In Mousementioning

confidence: 99%

Local Bradykinin Formation Is Controlled by Glycosaminoglycans

Renné

Schuh²,

Müller‐Esterl

2005

The Journal of Immunology

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Bradykinin is a potent inflammatory mediator that induces vasodilation, vascular leakage, and pain sensations. This short-lived peptide hormone is liberated from its large precursor protein high molecular weight kininogen (HK) through the contact system cascade involving coagulation factor XII and plasma kallikrein. Although bradykinin release is well established in vitro, the factors and mechanisms controlling bradykinin generation in vivo are still incompletely understood. In this study we demonstrate that binding of HK to glycosaminoglycans (GAGs) of the heparan and chondroitin sulfate type efficiently interferes with bradykinin release in plasma and on endothelial surfaces. Proteolytic bradykinin production on endothelial cells is restored following degradation of cell surface GAG through heparinase. Alternatively, application of HK fragments D3 or light chain, which compete with uncleaved HK for cell binding, promote kininogen proteolysis and bradykinin release. Intravital microscopy revealed that HK fragments increase bradykinin-mediated mesentery microvascular leakage. Topical application of D3 or light chain enhanced bradykinin generation and edema formation in the mouse skin. Our results demonstrate that bradykinin formation is controlled by HK binding to and detachment from GAGs. Separation of the precursor from cell surfaces is a prerequisite for its efficient proteolytic processing. By this means, fragments arising from HK processing propagate bradykinin generation, revealing a novel regulatory level for the kallikrein-kinin system.

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Inhibitory effects of cyclic AMP elevating agents on lipopolysaccharide (LPS)‐induced microvascular permeability change in mouse skin

Cited by 48 publications

References 22 publications

Evaluation of the colo-protective effects of tadalafil in an experimental model of ulcerative colitis in rats

Evaluation of the colo-protective effects of tadalafil in an experimental model of ulcerative colitis in rats

Lipopolysaccharide‐induced metastatic growth is associated with increased angiogenesis, vascular permeability and tumor cell invasion

Local Bradykinin Formation Is Controlled by Glycosaminoglycans

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