Lung morphology and growth of rats exposed to tobacco smoke and alcohol

Magnani, Karla Luciana; Catâneo, Daniele Cristina; Capelozzi, Vera Luíza; Defaveri, Júlio; Hasimoto, Érica Nishida; Catâneo, Antônio José Maria

doi:10.1590/s0102-86502012001000004

Cited by 5 publications

(5 citation statements)

References 16 publications

(10 reference statements)

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“…In contrast with its potent effects on fibroblasts, romidepsin had little effect on ATII cell number or lamellar bodies, suggesting minimal toxicity on this cell typ e . Lamellar bodies are storage organelles of pulmonary surfactant and their degeneration has been reported as a marker of toxicity and injury for the lung epithelium [ 44 – 46 ]. Our findings are consistent with studies of romidepsin in CTCL where no pulmonary toxicity was reported [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

et al. 2017

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Idiopathic pulmonary fibrosis (IPF) is a progressive disease that usually affects elderly people. It has a poor prognosis and there are limited therapies. Since epigenetic alterations are associated with IPF, histone deacetylase (HDAC) inhibitors offer a novel therapeutic strategy to address the unmet medical need. This study investigated the potential of romidepsin, an FDA-approved HDAC inhibitor, as an anti-fibrotic treatment and evaluated biomarkers of target engagement that may have utility in future clinical trials. The anti-fibrotic effects of romidepsin were evaluated both in vitro and in vivo together with any harmful effect on alveolar type II cells (ATII). Bronchoalveolar lavage fluid (BALF) from IPF or control donors was analyzed for the presence of lysyl oxidase (LOX). In parallel with an increase in histone acetylation, romidepsin potently inhibited fibroblast proliferation, myofibroblast differentiation and LOX expression. ATII cell numbers and their lamellar bodies were unaffected. In vivo, romidepsin inhibited bleomycin-induced pulmonary fibrosis in association with suppression of LOX expression. LOX was significantly elevated in BALF of IPF patients compared to controls. These data show the anti-fibrotic effects of romidepsin, supporting its potential use as novel treatment for IPF with LOX as a companion biomarker for evaluation of early on-target effects.

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Section: Discussionmentioning

confidence: 99%

The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

et al. 2017

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“…Hence, since the positions of the OCs are not adjustable, it has the possible limitation of yielding inaccurate SAB measurements for animals with body lengths greater than 26 cm. Indeed, it has been reported that male Wistar rats can attain an average body length of 28.2 ± 0.9 cm (SD, n = 14) when they reach a weight of 593 ± 65 g (Magnani et al, 2012). Despite the last possibility, it should be noted that the studies of continuous SAB in adult rats are usually performed in animals weighing no more than 300 g (Drew et al, 1973;Hefco et al, 2003;Krebs-Kraft & Parent, 2008;Stefani et al, 1999), presumably with a body length of less than 26 cm.…”

Section: Discussionmentioning

confidence: 99%

An automated Y-maze based on a reduced instruction set computer (RISC) microcontroller for the assessment of continuous spontaneous alternation in rats

et al. 2015

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Continuous spontaneous alternation behavior (SAB) in a Y-maze is used for evaluating working memory in rodents. Here, the design of an automated Y-maze equipped with three infrared optocouplers per arm, and commanded by a reduced instruction set computer (RISC) microcontroller is described. The software was devised for recording only true entries and exits to the arms. Experimental settings are programmed via a keyboard with three buttons and a display. The sequence of arm entries and the time spent in each arm and the neutral zone (NZ) are saved as a text file in a non-volatile memory for later transfer to a USB flash memory. Data files are analyzed with a program developed under LabVIEW® environment, and the results are exported to an Excel® spreadsheet file. Variables measured are: latency to exit the starting arm, sequence and number of arm entries, number of alternations, alternation percentage, and cumulative times spent in each arm and NZ. The automated Y-maze accurately detected the SAB decrease produced in rats by the muscarinic antagonist trihexyphenidyl, and its reversal by caffeine, having 100 % concordance with the alternation percentages calculated by two trained observers who independently watched videos of the same experiments. Although the values of time spent in the arms and NZ measured by the automated system had small discrepancies with those calculated by the observers, Bland-Altman analysis showed 95 % concordance in three pairs of comparisons, while in one it was 90 %, indicating that this system is a reliable and inexpensive alternative for the study of continuous SAB in rodents.

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“…Subsequent studies showed that both low birth weight (LBW) and respiratory infections in infancy were associated with decreased adult lung function and death from COPD [Barker et al 1991]. Evidence to support the concept of ‘foetal programming’, whereby insults during critical periods of development produce permanent structural, physiological or epigenetic changes with lifelong consequences [Miller and Marty, 2010; Barker, 2012], has also been provided by experimental animal models [Kallapur and Ikegami, 2006; Kramer et al 2009; Shimoda and Semenza, 2011; Abbott and Winzer-Serhan, 2012; Hilgendorff et al 2012; Magnani et al 2012; Maritz and Mutemwa, 2012; Sutherland et al 2012]. These studies have shown that insults to the developing lung during intrauterine or very early postnatal life lead to increased susceptibility to respiratory disease during both childhood and later life [Gluckman et al 2008; Harding and Maritz, 2012].…”

Section: Introductionmentioning

confidence: 99%

Early life influences on the development of chronic obstructive pulmonary disease

Stocks

Sonnappa

2013

Ther Adv Respir Dis

124

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There is increasing evidence that chronic obstructive pulmonary disease (COPD) is not simply a disease of old age that is largely restricted to heavy smokers, but may be associated with insults to the developing lung during foetal life and the first few years of postnatal life, when lung growth and development are rapid. A better understanding of the long-term effects of early life factors, such as intrauterine growth restriction, prenatal and postnatal exposure to tobacco smoke and other pollutants, preterm delivery and childhood respiratory illnesses, on the subsequent development of chronic respiratory disease is imperative if appropriate preventive and management strategies to reduce the burden of COPD are to be developed. The extent to which insults to the developing lung are associated with increased risk of COPD in later life depends on the underlying cause, timing and severity of such derangements. Suboptimal conditions in utero result in aberrations of lung development such that affected individuals are born with reduced lung function, which tends to remain diminished throughout life, thereby increasing the risk both of wheezing disorders during childhood and subsequent COPD in genetically susceptible individuals. If the current trend towards the ever-increasing incidence of COPD is to be reversed, it is essential to minimize risks to the developing lung by improvements in antenatal and neonatal care, and to reduce prenatal and postnatal exposures to environmental pollutants, including passive tobacco smoke. Furthermore, adult physicians need to recognize that lung disease is potentially associated with early life insults and provide better education regarding diet, exercise and avoidance of smoking to preserve precious reserves of lung function in susceptible adults. This review focuses on factors that adversely influence lung development in utero and during the first 5 years of life, thereby predisposing to subsequent COPD.

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Lung morphology and growth of rats exposed to tobacco smoke and alcohol

Cited by 5 publications

References 16 publications

The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

The histone deacetylase inhibitor, romidepsin, as a potential treatment for pulmonary fibrosis

An automated Y-maze based on a reduced instruction set computer (RISC) microcontroller for the assessment of continuous spontaneous alternation in rats

Early life influences on the development of chronic obstructive pulmonary disease

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