Fluoxetine Attenuates Chronic Methamphetamine‐induced Pulmonary Arterial Remodelling: Possible Involvement of Serotonin Transporter and Serotonin 1B Receptor

Liu, Ming; Wang, Yun; Wang, Hanming; Bai, Yang; Zhang, Xinhua; Sun, Yingxian; Wang, Huailiang

doi:10.1111/j.1742-7843.2012.00933.x

Cited by 26 publications

(23 citation statements)

References 26 publications

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“…On day 22, the rats in all the groups were anaesthetized with 3% pentobarbital sodium (40 mg/ kg). Systemic arterial pressure (SAP) and pulmonary arterial pressure (PAP) were recorded under the same conditions as previously described (22)(23)(24). The right carotid artery was isolated and cannulated with a polyethylene catheter to a fluid-filled force transducer.…”

Section: Assessment Of Pahmentioning

confidence: 99%

“…The pulmonary arteries (external diameter, 60-80 µm) were randomly selected for high-power (x400) evaluation. Pulmonary vascular remodeling was measured as the percentage of medial thickness, which was calculated according to previously described methods as follows: medial wall thickness (%) = (external diameter -internal diameter)/ external diameter) x100% (22); wall area (%) = (total vessel area -lumen area)/total vessel area x100% (25).…”

Section: Assessment Of Pahmentioning

confidence: 99%

“…The levels of Tph-1 and SERT protein were calculated as the average optical density. Immunohistochemical staining followed a basic indirect protocol using a citrate antigen-retrieval method (5,22).…”

Section: Assessment Of Pahmentioning

confidence: 99%

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4-Chloro-DL-phenylalanine protects against monocrotaline-induced pulmonary vascular remodeling and lung inflammation

Bai¹,

Wang²,

Liu³

et al. 2013

International Journal of Molecular Medicine

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The present study was performed to investigate the effects of 4-chloro-DL-phenylalanine (PCPA), a tryptophan hydroxylase (Tph) inhibitor (TphI), on pulmonary vascular remodeling and lung inflammation in monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats. Animal models of PAH were established using Sprague-Dawley (SD) rats by a single intraperitoneal injection of MCT (60 mg/kg). PCPA (50 or 100 mg/kg/day) was administered to the rats with PAH. On day 22, hemodynamic measurements and morphological observations of the lung tissues were performed. The levels of Tph-1 and serotonin transporter (SERT) in the lungs were analyzed by immunohistochemistry and western blot analysis. The expression of matrix metalloproteinase (MMP)-2 and MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 and inflammatory cytokines were assayed by western blot analysis. The activity of MMP-2 and MMP-9 was evaluated by gelatin zymography (GZ). MCT markedly promoted PAH, increased the right ventricular hypertrophy index, pulmonary vascular remodeling, lung inflammation and mortality, which was associated with the increased expression of Tph-1, SERT, MMP-2/-9, TIMP-1/-2 and inflammatory cytokines. PCPA markedly attenuated MCT-induced pulmonary vascular remodeling and lung inflammation, inhibited the expression of Tph-1 and SERT and suppressed the expression of MMP-2/-9, TIMP-1/-2, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α) and intercellular adhesion molecule-1 (ICAM-1). These findings suggest that the amelioration of MCT-induced pulmonary vascular remodeling and lung inflammation by PCPA is associated with the downregulation of Tph-1, SERT, MMP/TIMP and inflammatory cytokine expression in rats.

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Section: Assessment Of Pahmentioning

confidence: 99%

Section: Assessment Of Pahmentioning

confidence: 99%

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4-Chloro-DL-phenylalanine protects against monocrotaline-induced pulmonary vascular remodeling and lung inflammation

Bai¹,

Wang²,

Liu³

et al. 2013

International Journal of Molecular Medicine

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“…A previous study (11) reported that the inhibition of 5-HTR2a and 5-HTR2b had no effect on efferocytosis, although inhibiting SERT prevented 5-HT-impaired efferocytosis. A previous epidemiological study (12) suggested that MA abuse significantly increased the risk of developing pulmonary arterial hypertension (PAH). The disease severity and susceptibility to PAH may be associated with the increased SERT activity (13).…”

Section: Introductionmentioning

confidence: 99%

Fluoxetine protects against methamphetamine-induced lung inflammation by suppressing oxidative stress through the SERT/p38 MAPK/Nrf2 pathway in rats

Wang

Liu

et al. 2016

Molecular Medicine Reports

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Methamphetamine (MA) abuse is a major public health and safety concern throughout the world and a growing burden on healthcare costs. The purpose of the present study was to investigate the protective effect of fluoxetine against MA-induced chronic pulmonary inflammation and to evaluate the potential role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidative stress. Wistar rats were divided into control, MA and two fluoxetine-treated groups. Rats in the MA and the two fluoxetine-treated groups were treated daily with intraperitoneal injection of 10 mg/kg MA twice daily. Rats in the two fluoxetine-treated groups were injected intragastrically with fluoxetine (2 and 10 mg/kg) once daily, respectively. After 5 weeks, the rats were euthanized and hematoxylin and eosin staining, immunohistochemistry, western blot analysis and redox assay were performed. It was demonstrated that chronic exposure to MA can induce pulmonary inflammation in rats, with the symptoms of inflammatory cell infiltration, crowded lung parenchyma, thickened septum and a reduced number of alveolar sacs. Fluoxetine attenuated pulmonary inflammation and the expression of interleukin-6 and tumor necrosis factor-α in rat lungs. Fluoxetine inhibited MA-induced increases in the expression levels of serotonin transporter (SERT) and p-p38 mitogen-activated protein kinase (MAPK), and reversed the MA-induced decrease in nuclear Nrf2 and human heme oxygenase-1 in lungs. Fluoxetine at 10 mg/kg significantly reversed the reduced glutathione (GSH) level, the ratio of GSH/oxidized glutathione, and the reactive oxygen species level in rat lungs from the MA group. These findings suggested that fluoxetine, a SERT inhibitor, has a protective effect against MA-induced lung inflammation by suppressing oxidative stress through the SERT/p38 MAPK/Nrf2 pathway in rats.

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“…Thus, the 5-HT reuptake inhibition mediated by fluoxetine is also likely to be effective in animal models of obsessive--compulsive disorder (OCD) [91], panic-like behaviour [92], as well as in bulimia and anorexia nervosa [93]. Indeed, this drug was observed to be effective in pulmonary vascular remodelling induced by methamphetamine [94] and in relieving premenstrual syndrome [95]. However, like other findings with SSRI, fluoxetine had no effect reversing pain-related behaviours [96].…”

Section: Other Preclinical Studiesmentioning

confidence: 99%

Fluoxetine: a case history of its discovery and preclinical development

Pérez-Caballero

Torres-Sánchez

Bravo

et al. 2014

Expert Opinion on Drug Discovery

132

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Fluoxetine Attenuates Chronic Methamphetamine‐induced Pulmonary Arterial Remodelling: Possible Involvement of Serotonin Transporter and Serotonin 1B Receptor

Cited by 26 publications

References 26 publications

4-Chloro-DL-phenylalanine protects against monocrotaline-induced pulmonary vascular remodeling and lung inflammation

4-Chloro-DL-phenylalanine protects against monocrotaline-induced pulmonary vascular remodeling and lung inflammation

Fluoxetine protects against methamphetamine-induced lung inflammation by suppressing oxidative stress through the SERT/p38 MAPK/Nrf2 pathway in rats

Fluoxetine: a case history of its discovery and preclinical development

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