Fluoxetine inhibits monocrotaline-induced pulmonary arterial remodeling involved in inhibition of RhoA–Rho kinase and Akt signalling pathways in rats

2012 ◽  
Vol 90 (11) ◽  
pp. 1506-1515 ◽  
Author(s):  
Han-Ming Wang ◽  
Yun Wang ◽  
Ming Liu ◽  
Yang Bai ◽  
Xin-Hua Zhang ◽  
...  
Keyword(s):  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Small Gtpase ◽  
Signalling Pathway ◽  
Selective Serotonin ◽  
Signalling Pathways ◽  
Arterial Remodeling ◽  
Pulmonary Arterial

Activation of the small GTPase Ras homolog gene family member A (RhoA) and Rho-associated kinase (ROCK) are important in the pathogenesis of pulmonary arterial hypertension (PAH). Selective serotonin reuptake inhibitors inhibit activation of RhoA and ROCK in vitro, and ameliorate PAH and pulmonary arterial remodeling in vivo. However, little is known about whether the RhoA–ROCK signalling pathway is involved in the treatment of PAH with fluoxetine in vivo. The aim of the present study was to investigate the involvement of the RhoA–ROCK signalling pathway in the protective effect of the selective serotonin reuptake inhibitor fluoxetine against monocrotaline (MCT)-induced pulmonary arterial remodeling. MCT was applied to establish PAH in male Wistar rats. Fluoxetine was administered by gastric gavage once a day for 21 d. The results showed that MCT induced pulmonary arterial remodeling, raised the serotonylation and membrane translocation of RhoA in the lungs, and increased serotonin transporter (5-HTT), RhoA, and ROCK2 expression, and extracellular signal-regulated kinase (ERK) and Akt phosphorylation in the pulmonary arteries and the lungs. Fluoxetine markedly inhibited these MCT-induced changes. The findings suggest that fluoxetine inhibits MCT-induced pulmonary arterial remodeling in rats by inhibition of the RhoA–ROCK and Akt signalling pathways.

The adverse skeletal effects of selective serotonin reuptake inhibitors

2012 ◽  
Vol 27 (3) ◽  
pp. 156-169 ◽  
Author(s):  
E.M. Tsapakis ◽  
Z. Gamie ◽  
G.T. Tran ◽  
S. Adshead ◽  
A. Lampard ◽  
...  
Keyword(s):  
Bone Formation ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Mineral Density ◽  
Increased Risk ◽  
Risk Of Falls

AbstractSelective serotonin reuptake inhibitors (SSRIs) are a widely used group of antidepressants (ADs) with reported potential detrimental effects on bone mineral density (BMD) and increased fracture risk. Here, a comprehensive review of the in vitro, in vivo and clinical studies to date was carried out using the medical search engines MEDLINE (1950 to September 2010) and EMBASE (1980 to September 2010). Serotonin (5-HT) receptors have been identified on osteoclast, osteoblast and osteocyte cell lines. The effect of SSRIs on bone formation and resorption appears to be governed by the activation of a number of 5-HT receptors on osteoblasts and osteoclasts via endocrine, autocrine/paracrine and neuronal pathways. In vitro, in vivo and clinical collective data appears to indicate that SSRIs have a negative effect on bone at the therapeutic dose levels widely used for the treatment of depression in current clinical practice. Caution may therefore have to be employed with the use of SSRIs in patients at an increased risk of falls and osteoporosis. Further studies are needed in order to fully elicit the role of SSRIs in bone formation and their effects in the low oestrogen state.

scholarly journals Mutual promotion of FGF21 and PPARγ attenuates hypoxia-induced pulmonary hypertension

2019 ◽  
Vol 244 (3) ◽  
pp. 252-261 ◽  
Author(s):  
Gexiang Cai ◽  
Jingjing Liu ◽  
Meibin Wang ◽  
Lihuang Su ◽  
Mengsi Cai ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Mouse Lung ◽  
Fibroblast Growth Factor 21 ◽  
Arterial Remodeling ◽  
Collagen Deposition ◽  
Pparγ Agonist ◽  
Pulmonary Arterial ◽  
The Relationship

Fibroblast growth factor 21 (FGF21), a primarily liver-derived endocrine factor, has the beneficial effect of protecting blood vessels. Peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated nuclear transcription factor, has been reported to effectively inhibit pulmonary hypertension (PH). The purpose of this study is to investigate the role of FGF21 in hypoxia-induced PH (HPH) and explore the relationship between FGF21 and PPARγ in this disorder. Adult C57BL/6 mice were subjected to four weeks of hypoxia to establish a PH model. The effects of FGF21 and PPARγ agonists and antagonists were investigated in HPH mice, as well as the relationship between FGF21 and PPARγ in this model. Moreover, we investigated the underlying mechanisms of this relationship between FGF21 and PPARγ in vivo and in vitro. In vivo, we found that hypoxia resulted in pulmonary hypertension, right ventricular hypertrophy, pulmonary arterial remodeling, and pulmonary arterial collagen deposition. Furthermore, hypoxia decreased FGF21 and PPARγ levels. These changes were reversed by exogenous FGF21 and a PPARγ agonist and were further enhanced by a PPARγ antagonist. The hypoxia-induced decrease in β-klotho (KLB) expression was improved by the PPARγ agonist and further reduced by the PPARγ antagonist. Exogenous FGF21 increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation (Thr172) and PPARγ coactivator-1α (PGC-1α) expression in PH mouse lung homogenates. In vitro, we found that knockdown of AMPK or using an AMPK antagonist inhibited the FGF21-mediated up-regulation of PPARγ expression, and the PPARγ-mediated up-regulation of FGF21 expression was inhibited by knockdown of KLB. These results indicated that FGF21 exerts protective effects in inhibiting HPH. FGF21 and PPARγ mutually promote each other’s expression in HPH via the AMPK/PGC-1α pathway and KLB protein. Impact statement In this study, we reported for the first time that FGF21 alleviated hypoxia-induced pulmonary hypertension through attenuation of increased pulmonary arterial pressure, pulmonary arterial remodeling and collagen deposition in vivo, and we confirmed the mutual promotion of FGF21 and PPARγ in hypoxia-induced pulmonary hypertension. Additionally, we found that FGF21 and PPARγ mutually promote each other’s expression via the AMPK/PGC-1α pathway and KLB protein in vitro and in vivo. Pulmonary hypertension is a progressive and serious pathological phenomenon with a poor prognosis, and current therapies are highly limited. Our results provide novel insight into potential clinical therapies for pulmonary hypertension and establish the possibility of using this drug combination and potential dosage reductions in clinical settings.

Effect of selective serotonin reuptake inhibitors on in vitro fertilization outcome

2009 ◽  
Vol 92 (4) ◽  
pp. 1312-1314 ◽  
Author(s):  
Brooke E. Friedman ◽  
Jayna L. Rogers ◽  
Lora K. Shahine ◽  
Lynn M. Westphal ◽  
Ruth B. Lathi
Keyword(s):  
In Vitro Fertilization ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Vitro Fertilization

Selective Serotonin Reuptake Inhibitors and Pulmonary Arterial Hypertension

CHEST Journal ◽  
2012 ◽  
Vol 141 (2) ◽  
pp. 348-353 ◽  
Author(s):  
Irfan A. Dhalla ◽  
David N. Juurlink ◽  
Tara Gomes ◽  
John T. Granton ◽  
Hong Zheng ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Pulmonary Arterial

scholarly journals Paroxetine and bupropion have no in vitro effects on lynphocyte proliferation and viability

2007 ◽  
Vol 56 (2) ◽  
pp. 116-119 ◽  
Author(s):  
Ramiro Ronchetti ◽  
Mariana Dal Pizzol ◽  
Rodrigo Pestana Lopes ◽  
Rachel Rubin da Silva ◽  
Gabriel José Chittó Gauer ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Cell Viability ◽  
Reuptake Inhibitor ◽  
Peripheral Blood ◽  
Serotonin Reuptake ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Selective Serotonin ◽  
Favorable Effect ◽  
Immunological Effects

OBJECTIVE: Initial studies with tricyclic antidepressants demonstrated that they jeopardize the immune system activity. Recent studies suggested that selective serotonin reuptake inhibitors would have stimulating immunological effects. Here, we explored the in vitro immunological effects of two antidepressants used in clinical practice, paroxetine (selective serotonin reuptake inhibitor) and bupropion (norepinephrine and dopamine reuptake inhibitor). METHOD: Peripheral blood samples were obtained from 16 healthy volunteers and the peripheral blood mononuclear cells were isolated and cultured in vitro. We evaluated the effects of bupropion and paroxetine on cell viability as well as the ability to suppress phytohemagglutinin-induced lymphocyte proliferation. RESULTS: Both antidepressants produced neither significant effect on cell viability nor on T-cell proliferation. CONCLUSIONS: This could be of valuable information for the clinical practice when these drugs are administered. These results indicate a more favorable effect of such psychopharmacological drugs when compared to reported immunological effects associated with tryciclic antidepressants.

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