In Vitro effects of tamoxifen on equine neutrophils

Borlone, C; Morales, Natalia; Henríquez, Claudio; Folch, Hugo; Olave, Carla; Sarmiento, José; Uberti, Benjamín; Morán, Gabriel

doi:10.1016/j.rvsc.2016.11.003

Cited by 16 publications

(20 citation statements)

References 49 publications

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“…Simvastatin, as an effective serum cholesterol-lowering agent could reduce the percentage of neutrophil in BALF and improve airway inflammation and remodeling in obese asthma mice [81]. Tamoxifen had a direct action on equine peripheral blood neutrophils and dampened the respiratory burst production [82]. Rosiglitazone (RSG), a peroxisome proliferator-activated receptor- γ agonist, has been reported to attenuate airway inflammation by inhibiting the proliferation of effector T cells in a murine model of neutrophilic asthma in vivo [48].…”

Section: Asthmatic Neutrophilsmentioning

confidence: 99%

Advanced Role of Neutrophils in Common Respiratory Diseases

Liu

Pang

Wang

et al. 2017

Journal of Immunology Research

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Respiratory diseases, always being a threat towards the health of people all over the world, are most tightly associated with immune system. Neutrophils serve as an important component of immune defense barrier linking innate and adaptive immunity. They participate in the clearance of exogenous pathogens and endogenous cell debris and play an essential role in the pathogenesis of many respiratory diseases. However, the pathological mechanism of neutrophils remains complex and obscure. The traditional roles of neutrophils in severe asthma, chronic obstructive pulmonary diseases (COPD), pneumonia, lung cancer, pulmonary fibrosis, bronchitis, and bronchiolitis had already been reviewed. With the development of scientific research, the involvement of neutrophils in respiratory diseases is being brought to light with emerging data on neutrophil subsets, trafficking, and cell death mechanism (e.g., NETosis, apoptosis) in diseases. We reviewed all these recent studies here to provide you with the latest advances about the role of neutrophils in respiratory diseases.

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Section: Asthmatic Neutrophilsmentioning

confidence: 99%

Advanced Role of Neutrophils in Common Respiratory Diseases

Liu

Pang

Wang

et al. 2017

Journal of Immunology Research

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“…The few clinical studies that have looked into the potential use of TAM for equine airway inflammation have been based on a single dosage (approximately 0,25 mg/kg) extrapolated from human medicine, with conflicting results regarding clinical efficacy based on that single empirical dose [15,16]. However, there is robust pre-clinical information on modulation of inflammation, which warrants the pharmacokinetic and safety data presented here [17][18][19][20][21]. Oral TAM absorption was similar to findings in other species, since plasma concentration of TAM was maximum 3 h after oral administration, comparably to reports in humans and mice, where maximum concentration is also reached between 4 and 9 h postadministration [1].…”

Section: Discussionmentioning

confidence: 94%

Tamoxifen in horses: pharmacokinetics and safety study

et al. 2019

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Background Tamoxifen (TAM), a selective modulator of estrogen receptors (SERMs) has been recently explored as a therapeutic option for the oral treatment of airway inflammation in the horse. The objective of this work was to establish pharmacokinetic parameters of TAM and its main metabolites in equines, as well as to determine its clinical safety in short-term treatments. Results We determined TAM and its three main metabolites (4-OH tamoxifen, endoxifen, and N-desmethyl tamoxifen) in plasma after single administration of 0.25 mg/kg in healthy adult horses ( n = 12). A maximum concentration of TAM was achieved 3 h after the oral administration (4.65 pg/mL ± 1.69); 4-OH tamoxifen was the metabolite that reached the highest concentration (78 pg/mL ± 70), followed by N-desmethyl tamoxifen (0.43 pg / mL ± 0.48), and finally endoxifen (0.17 pg/mL ± 0.17). All metabolites showed peak concentration 2 h after oral administration of the drug. Oral TAM bioavailability was 13,15% ± 4,18, with a steady state volume of distribution of 7831 ± 2922 (L/kg). Elimination half-life was 15.40 ± 5.80 h, and clearance was 5876 ± 699 (mL/kg/min). Clinical safety of TAM was determined over a 7-day course of treatment (0.25 mg/kg, orally q 24 h, n = 20). No adverse effects were observed through clinical examination, blood hematology, serum biochemistry, ophthalmological and reproductive examinations. Endometrial edema observed in some mares was attributed to normal cyclic activity. Conclusions Tamoxifen has moderate oral bioavailability and a large volume of distribution, with three main metabolites in horses. Additionally, oral TAM administration over a 7-day treatment period demonstrated to be clinically safe, without adverse effects on clinical, hematological or serum biochemical parameters. These data could contribute to the continued research into this drug’s potential for the treatment of different inflammatory conditions in equine species. Electronic supplementary material The online version of this article (10.1186/s13620-019-0143-7) contains supplementary material, which is available to authorized users.

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“…The effects of tamoxifen on neutrophils are controversial with in vitro studies suggesting an anti‐inflammatory effect by the induction of apoptosis, a reduction of the chemotactic response and respiratory burst production, a decreased production of 5‐lipoxygenase and a diminution of the neutrophilic infiltration to the site of injury . In contrast, other experiments have shown activation of neutrophils by an enhancement of their chemotaxis, phagocytic and bactericidal activity, and neutrophil extracellular traps (NETs) formation .…”

Section: Discussionmentioning

confidence: 99%

“…As estrogen administration has been associated with both improvement and, contrariwise, to the development of asthma in women, studying the impact of an estrogen receptor modulator could help delineate the role of sex hormones in asthma . Recently, it showed promising results for the treatment of severe equine asthma by reducing the neutrophilic chemotactic response and respiratory burst production and by inducing apoptosis of peripheral and pulmonary neutrophils in vitro . Tamoxifen was also studied in healthy adult horses in which an asthma‐like inflammation was experimentally reproduced by exposure to Aspergillus fumigatus contaminated hay.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of tamoxifen for the treatment of severe equine asthma

Mainguy-Seers

Picotte

Lavoie

2018

Veterinary Internal Medicne

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BackgroundTamoxifen, a selective estrogen receptor modulator, decreased airway neutrophilia and improved clinical signs in an experimental model of equine asthma, and induced neutrophilic apoptosis in vitro.Hypothesis/ObjectivesTamoxifen reduces airway neutrophilia and improves lung function in severe asthmatic horses.AnimalsTwelve severe asthmatic horses from a research herd.MethodsRandomized controlled blinded study design. The effects of a 12‐day oral treatment with tamoxifen (0.22 mg/kg, q24h) or dexamethasone (0.06 mg/kg, q24h) on lung function, endoscopic tracheal mucus score and bronchoalveolar lavage fluid cytology were compared.ResultsTamoxifen significantly improved the pulmonary resistance (R L; mean reduction of 1.15 cm H2O/L/s [CI: 0.29‐2.01, P = .007] on day 13), but had no effect on the other variables evaluated. Dexamethasone normalized lung function (mean reduction of R L of 2.48 cm H2O/L/s [CI: 1.54‐3.43, P < .0001] on day 13), without affecting airway neutrophilia.Conclusions and Clinical ImportanceResults of this study do not support the use of tamoxifen at the dose studied as an antineutrophilic medication in the treatment of asthmatic horses in chronic exacerbation.

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In Vitro effects of tamoxifen on equine neutrophils

Cited by 16 publications

References 49 publications

Advanced Role of Neutrophils in Common Respiratory Diseases

Advanced Role of Neutrophils in Common Respiratory Diseases

Tamoxifen in horses: pharmacokinetics and safety study

Efficacy of tamoxifen for the treatment of severe equine asthma

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