Tezosentan Attenuates Organ Injury and Mesenteric Blood Flow Decrease in Endotoxemia and Cecal Ligation and Puncture

Erdem, Ayşen; Sevgili, Ayşe Meltem; Akbıyık, Filiz; Atilla, Pergin; Çakar, Nur; Balkanci, Zeynep Dicle; İskit, Alper B.; Güç, M. Oğuz

doi:10.1016/j.jss.2006.08.028

Cited by 10 publications

(7 citation statements)

References 38 publications

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“…Light microscopic examination showed dilated congested marginal blood sinusoids in the spleen. This result is consistent with a recent study pointed out that tezosentan, a dual endothelin ETA/ETB receptor antagonist, caused venous sinusoidal dilation in the spleen [43].…”

Section: Discussionsupporting

confidence: 93%

Blocking Type I Interferon (IFN) Signaling Impairs Antigen Responsiveness of Circulating Lymphocytes and Alters Their Homing to Lymphoid Organs: Protective Role of Type I IFN

Badr

Waly

Eldien

et al. 2010

Cell Physiol Biochem

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Background: We recently demonstrated that type I Interferon (IFN) rescues in vitro, human B-lymphocytes from apoptosis via PI3Kδ/Akt, Rho-A, NFĸB and Bcl-2/BclXL. In the present study we extended our work to clarify, in vivo, the role of type I IFN signalling on the circulating and lymphoid organs homing lymphocytes. Methodology: Two groups of mice 13 in each were set: type I IFN signalling blocked mice injected with anti-IFNAR1 antagonist antibody (10 mg/kg body weight) once/day for up to 20 days, and control group were injected with vehicle alone. Results: Flow cytometry analysis to monitor the blood lymphocyte phenotype and proliferation have shown a significant decrease in CD45R/CD220⁺ B cells, CD4⁺ and CD8⁺ T cells in treated animals. Furthermore, the proliferative capacities of these lymphocyte subsets were significantly decreased in treated animals compared to those of control mice. Marked reduction in the plasma levels of IL-2 and IL-7 (cytokines important for the development of T and B cells) but not of IL-6 or IL-10 was observed in treated mice and this may a cause for emergence decrease in B and T cell numbers. Immunohistochemical studies have further shown a marked reduction in the numbers of CD20⁺ B cells in spleen and Peyer’s patches and CD3⁺ T cells in thymus of treated animals. Moreover, electron microscopy examinations have revealed a loss of lymphocytes with characteristic features of apoptosis. Conclusion: Our data confirmed that the in vivo inhibition of type I IFN signaling induce decrease in the numbers and defective functions of circulating and lymphoid organs homing lymphocytes providing a strong evidence for the protective effects of type 1 IFNs (IFN-α/ β) on B and T lymphocytes.

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Section: Discussionsupporting

confidence: 93%

Blocking Type I Interferon (IFN) Signaling Impairs Antigen Responsiveness of Circulating Lymphocytes and Alters Their Homing to Lymphoid Organs: Protective Role of Type I IFN

Badr

Waly

Eldien

et al. 2010

Cell Physiol Biochem

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“…Decrease of mesenteric blood flow leads to impaired intestinal barrier integrity and therefore translocation of microorganisms into the bloodstream. Spread of the microorganisms triggers massive and uncontrolled release of inflammatory cytokines and subsequent free radicals which ultimately causes negative effects on the vessels and multiple organs (Balzan et al 2007;Erdem et al 2007;Koh et al 2002;Yuksel et al 2009). …”

Section: Discussionmentioning

confidence: 99%

Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats

Ozer

Göktaş

Kılınç

et al. 2017

Can. J. Physiol. Pharmacol.

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Keyword:infliximab, sepsis, survival, multiple organ dysfunction, vascular reactivity and mesenteric arterial blood flow https://mc06.manuscriptcentral.com/cjpp-pubs AbstractTumor necrosis factor-alpha (TNF-α) is a pivotal mediator that triggers inflammatory process, oxidative stress and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, oxidative and inflammatory injuries in cecal ligation and puncture (CLP) induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, CLP+infliximab subgroups. 24 hours before the operations rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg). 20 hours after operations MBF and phenylephrine responses of isolated aortic rings were measured. Tissue damages were examined biochemically and histopathologically. showed protective effects in sepsis due to its improvement effects on mesenteric perfusion, aortic function and its anti-inflammatory and antioxidative effects.

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“…Endothelin receptor antagonists have been evaluated in different animal models of ALI/ARDS. While studies have shown that they have protective effects in some models of ALI/ARDS [12,13,40–42], their efficacy may vary in different experimental models of lung injury or following different modes of administration. This was reflected in a study by Hubloue et al.…”

Section: Discussionmentioning

confidence: 99%

Effect of the endothelin receptor antagonist tezosentan on alpha‐naphthylthiourea‐induced lung injury in rats

Atalay

Yurdakan

Yilmaz-Sipahi

2012

The Kaohsiung J of Med Scie

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Acute lung injury is an inflammatory syndrome that increases the permeability of the blood-gas barrier, resulting in high morbidity and mortality. Despite intensive research, treatment options remain limited. We investigated the protective efficacy of tezosentan, a novel, dual endothelin receptor antagonist, in an experimental model of alpha-naphthylthiourea (ANTU)-induced acute lung injury in rats. ANTU was intraperitoneally (i.p.) injected into rats at a dose of 10 mg/kg. Tezosentan was injected 30 minutes before ANTU was subcutaneously (s.c.) injected at doses of 2, 10, or 30 mg/kg, 60 minutes before ANTU was injected at doses of 2, 10, or 30 mg/kg (i.p.), and 90 minutes before ANTU at a dose of 10 mg/kg (i.p.). Four hours later, the lung weight/body weight (LW/BW) ratio and pleural effusion (PE) were measured. When injected 30 minutes before ANTU at doses of 2, 10, or 30 mg/kg (s.c.), tezosentan had no effect on lung pathology. When injected 60 minutes before ANTU at doses of 2, 10, or 30 mg/kg (i.p.) or 90 minutes before ANTU (10 mg/kg, i.p.), tezosentan significantly decreased the PE/BW ratio and had a prophylactic effect on PE formation at all doses. Therefore, tezosentan may attenuate lung injury. Furthermore, its acute and inhibitory effects on fluid accumulation were more effective in the pleural cavity than in the interstitial compartment in this experimental model.

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Tezosentan Attenuates Organ Injury and Mesenteric Blood Flow Decrease in Endotoxemia and Cecal Ligation and Puncture

Cited by 10 publications

References 38 publications

Blocking Type I Interferon (IFN) Signaling Impairs Antigen Responsiveness of Circulating Lymphocytes and Alters Their Homing to Lymphoid Organs: Protective Role of Type I IFN

Blocking Type I Interferon (IFN) Signaling Impairs Antigen Responsiveness of Circulating Lymphocytes and Alters Their Homing to Lymphoid Organs: Protective Role of Type I IFN

Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats

Effect of the endothelin receptor antagonist tezosentan on alpha‐naphthylthiourea‐induced lung injury in rats

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