Metabolomics of lung microdissections reveals region- and sex-specific metabolic effects of acute naphthalene exposure in mice

2021 ◽  
Author(s):  
Nathanial C Stevens ◽  
Patricia C Edwards ◽  
Lisa M Tran ◽  
Xinxin Ding ◽  
Laura S Van Winkle ◽  
...  
Keyword(s):  
Fossil Fuels ◽  
Metabolic Effects ◽  
Mouse Lung ◽  
Female Mice ◽  
Novel Approach ◽  
Metabolite Profiles ◽  
Treatment Data ◽  
Induced Changes ◽  
Conducting Airways ◽  
Metabolite Abundance

Abstract Naphthalene is a ubiquitous environmental contaminant produced by combustion of fossil fuels and is a primary constituent of both mainstream and side stream tobacco smoke. Naphthalene elicits region-specific toxicity in airway club cells through cytochrome P450 (P450)-mediated bioactivation, resulting in depletion of glutathione and subsequent cytotoxicity. While effects of naphthalene in mice have been extensively studied, few experiments have characterized global metabolomic changes in the lung. In individual lung regions, we found metabolomic changes in microdissected mouse lung conducting airways and parenchyma obtained from animals sacrificed at three timepoints following naphthalene treatment. Data on 577 unique identified metabolites were acquired by accurate mass spectrometry-based assays focusing on lipidomics and non-targeted metabolomics of hydrophilic compounds. Statistical analyses revealed distinct metabolite profiles between the two lung regions. Additionally, the number and magnitude of statistically significant exposure-induced changes in metabolite abundance were different between airways and parenchyma for unsaturated lysophosphatidylcholines (LPCs), dipeptides, purines, pyrimidines, and amino acids. Importantly, temporal changes were found to be highly distinct for male and female mice, with males exhibiting predominant treatment-specific changes only at two hours post-exposure. In females, metabolomic changes persisted until six hours post-naphthalene treatment, which may explain the previously characterized higher susceptibility of female mice to naphthalene toxicity. In both males and females, treatment-specific changes corresponding to lung remodeling, oxidative stress response, and DNA damage were observed. Overall, this study provides insights into potential mechanisms contributing to naphthalene toxicity and presents a novel approach for lung metabolomic analysis that distinguishes responses of major lung regions.

scholarly journals Metabolomics of lung microdissections reveals region- and sex-specific metabolic effects of acute naphthalene exposure in mice

2021 ◽  
Author(s):  
Nathanial Chase Stevens ◽  
Patricia C Edwards ◽  
Lisa M Tran ◽  
Xinxin Ding ◽  
Laura S Van Winkle ◽  
...  
Keyword(s):  
Fossil Fuels ◽  
Metabolic Effects ◽  
Mouse Lung ◽  
Female Mice ◽  
Metabolite Profiles ◽  
Treatment Data ◽  
Induced Changes ◽  
Conducting Airways ◽  
Lung Airways ◽  
Metabolite Abundance

Naphthalene is a ubiquitous environmental contaminant produced by combustion of fossil fuels and is a primary constituent of both mainstream and side stream tobacco smoke. Naphthalene elicits region-specific toxicity in airway club cells through cytochrome P450 (P450)-mediated bioactivation, resulting in depletion of glutathione and subsequent cytotoxicity. While effects of naphthalene in mice have been extensively studied, few experiments have characterized global metabolomic changes in the lung. In individual lung regions, we found metabolomic changes in microdissected mouse lung conducting airways and parenchyma obtained from animals sacrificed 2, 6, and 24 hours following naphthalene treatment. Data on 577 unique identified metabolites were acquired by accurate mass spectrometry-based assays focusing on lipidomics and non-targeted metabolomics of hydrophilic compounds. Statistical analyses revealed distinct metabolite profiles between the two major lung regions. In addition, the number and magnitude of statistically significant exposure-induced changes in metabolite abundance were different between lung airways and parenchyma for unsaturated lysophosphatidylcholines (LPCs), dipeptides, purines, pyrimidines, and amino acids. Importantly, temporal changes were found to be highly distinct for male and female mice, with males exhibiting predominant treatment-specific changes only at two hours post-exposure. In females, metabolomic changes persisted until six hours post-naphthalene treatment, which may explain the previously characterized higher susceptibility of female mice to naphthalene toxicity. In both males and females, treatment-specific changes corresponding to lung remodeling, oxidative stress response, and DNA damage were observed, which may provide insights into potential mechanisms contributing to the previously reported effects of naphthalene exposure in the lung.

Methacholine-induced bronchoconstriction in dogs: effects of lung volume and O3 exposure

1988 ◽  
Vol 65 (6) ◽  
pp. 2679-2686 ◽  
Author(s):  
S. T. Kariya ◽  
S. A. Shore ◽  
W. A. Skornik ◽  
K. Anderson ◽  
R. H. Ingram ◽  
...  
Keyword(s):  
Lung Volume ◽  
Maximal Response ◽  
Maximal Effect ◽  
Response Curves ◽  
Lung Volumes ◽  
Before And After ◽  
Residual Capacity ◽  
Induced Changes ◽  
Conducting Airways ◽  
Concentration Response Curve

The maximal effect induced by methacholine (MCh) aerosols on pulmonary resistance (RL), and the effects of altering lung volume and O3 exposure on these induced changes in RL, was studied in five anesthetized and paralyzed dogs. RL was measured at functional residual capacity (FRC), and lung volumes above and below FRC, after exposure to MCh aerosols generated from solutions of 0.1-300 mg MCh/ml. The relative site of response was examined by magnifying parenchymal [RL with large tidal volume (VT) at fast frequency (RLLS)] or airway effects [RL with small VT at fast frequency (RLSF)]. Measurements were performed on dogs before and after 2 h of exposure to 3 ppm O3. MCh concentration-response curves for both RLLS and RLSF were sigmoid shaped. Alterations in mean lung volume did not alter RLLS; however, RLSF was larger below FRC than at higher lung volumes. Although O3 exposure resulted in small leftward shifts of the concentration-response curve for RLLS, the airway dominated index of RL (RLSF) was not altered by O3 exposure, nor was the maximal response using either index of RL. These data suggest O3 exposure does not affect MCh responses in conducting airways; rather, it affects responses of peripheral contractile elements to MCh, without changing their maximal response.

scholarly journals Deletion of Rptor in pre‐osteoblasts reveals a role for the mTORC1 complex in dietary‐induced changes to bone mass and glucose homeostasis in female mice

JBMR Plus ◽  
2021 ◽  
Author(s):  
Pawanrat Tangseefa ◽  
Sally K. Martin ◽  
Agnieszka Arthur ◽  
Vasilios Panagopoulos ◽  
Amanda J. Page ◽  
...  
Keyword(s):  
Bone Mass ◽  
Glucose Homeostasis ◽  
Female Mice ◽  
Induced Changes

scholarly journals Immunolocalization of Sonic Hedgehog (Shh) in Developing Mouse Lung

2001 ◽  
Vol 49 (12) ◽  
pp. 1593-1603 ◽  
Author(s):  
Leigh-Anne D. Miller ◽  
Susan E. Wert ◽  
Jeffrey A. Whitsett
Keyword(s):  
Epithelial Cells ◽  
Sonic Hedgehog ◽  
Normal Development ◽  
Clara Cell ◽  
Mouse Lung ◽  
Lung Hypoplasia ◽  
Hepatocyte Nuclear Factor ◽  
Clara Cells ◽  
Lung Morphogenesis ◽  
Conducting Airways

Expression of sonic hedgehog (Shh) is required for normal development of the lung during embryogenesis. Loss of Shh expression in mice results in tracheoesophageal fistula, lung hypoplasia, and abnormal lung lobulation. To determine whether Shh may play a role later in lung morphogenesis, immunostaining for Shh was performed in mouse lung from embryonic day (E) 10.5 to postnatal day (PD) 24. Shh was detected in the distal epithelium of the developing mouse lung from E10.5 to E16.5. From E16.5 until PD15, Shh was present in epithelial cells in both the peripheral and conducting airways. Although all cells of the developing epithelium uniformly expressed Shh at E10.5, Shh expression was restricted to subsets of epithelial cells by E16.5. Between E16.5 and PD15, non-uniform Shh staining of epithelial cells was observed in the conducting airways in a pattern consistent with the distribution of non-ciliated bronchiolar cells (i.e., Clara cells) and the Clara cell marker CCSP. Shh did not co-localize with hepatocyte nuclear factor/forkhead homologue-4 (HFH-4), β-tubulin, or with the presence of cilia. These results support the concept that Shh plays a distinct regulatory role in the lung later in morphogenesis, when it may influence formation or cytodifferentiation of the conducting airways.

Comparative Proteomic Analysis of Radiation-Induced Changes in Mouse Lung: Fibrosis-Sensitive and -Resistant Strains

2008 ◽  
Vol 169 (4) ◽  
pp. 417-425 ◽  
Author(s):  
Xiaoping Ao ◽  
David M. Lubman ◽  
Mary A. Davis ◽  
Xianying Xing ◽  
Feng-Ming Kong ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Lung Fibrosis ◽  
Mouse Lung ◽  
Comparative Proteomic Analysis ◽  
Radiation Induced ◽  
Resistant Strains ◽  
Induced Changes

Epigenetic regulation of genes in learning and memory

2010 ◽  
Vol 48 ◽  
pp. 263-274 ◽  
Author(s):  
Tania L. Roth ◽  
Eric D. Roth ◽  
J. David Sweatt
Keyword(s):  
Learning And Memory ◽  
Cognitive Dysfunction ◽  
Epigenetic Regulation ◽  
Memory Formation ◽  
Covalent Modification ◽  
Gene Activity ◽  
Neural Function ◽  
Post Translational Modifications ◽  
Novel Approach ◽  
Induced Changes

Rapid advances in the field of epigenetics are revealing a new way to understand how we can form and store strong memories of significant events in our lives. Epigenetic modifications of chromatin, namely the post-translational modifications of nuclear proteins and covalent modification of DNA that regulate gene activity in the CNS (central nervous system), continue to be recognized for their pivotal role in synaptic plasticity and memory formation. At the same time, studies are correlating aberrant epigenetic regulation of gene activity with cognitive dysfunction prevalent in CNS disorders and disease. Epigenetic research, then, offers not only a novel approach to understanding the molecular transcriptional mechanisms underlying experience-induced changes in neural function and behaviour, but potential therapeutic treatments aimed at alleviating cognitive dysfunction. In this chapter, we discuss data regarding epigenetic marking of genes in adult learning and memory formation and impairment thereof, as well as data showcasing the promise for manipulating the epigenome in restoring memory capacity.

scholarly journals Oestrogen replacement fails to fully revert ovariectomy-induced changes in adipose tissue monoglycerides, diglycerides and cholesteryl esters of rats fed a lard-enriched diet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Valter Tadeu Boldarine ◽  
Ellen Joyce ◽  
Amanda Paula Pedroso ◽  
Mônica Marques Telles ◽  
Lila Missae Oyama ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Neutral Lipids ◽  
Saturated Fat ◽  
Metabolic Effects ◽  
Cholesteryl Esters ◽  
Ovx Rats ◽  
Lipid Species ◽  
Retroperitoneal White Adipose Tissue ◽  
Induced Changes

AbstractMenopause may be accompanied by abdominal obesity and inflammation, conditions accentuated by high-fat intake, especially of saturated fat (SFA)-rich diets. We investigated the consequences of high-SFA intake on the fatty acid (FA) profile of monoglycerides, diglycerides and cholesteryl esters from retroperitoneal white adipose tissue (RET) of rats with ovariectomy-induced menopause, and the effect of oestradiol replacement. Wistar rats were either ovariectomized (Ovx) or sham operated (Sham) and fed either standard chow (C) or lard-enriched diet (L) for 12 weeks. Half of the Ovx rats received 17β-oestradiol replacement (Ovx + E2). Body weight and food intake were measured weekly. RET neutral lipids were chromatographically separated and FAs analysed by gas chromatography. Ovariectomy alone increased body weight, feed efficiency, RET mass, leptin and insulin levels, leptin/adiponectin ratio, HOMA-IR and HOMA-β indexes. OvxC + E2 showed attenuation in nearly all blood markers. HOMA-β index was restored in OvxL + E2. OvxC showed significantly disturbed SFA and polyunsaturated FA (PUFA) profile in RET cholesteryl esters (CE). OvxC also showed increased monounsaturated FA (MUFA) in the monoglyceride diglyceride (Mono–Di) fraction. Similar changes were not observed in OvxL, although increased SFA and decreased PUFA was observed in Mono–Di. Overall, HRT was only partially able to revert changes induced by ovariectomy. There appears to be increased mobilization of essential FA in Ovx via CE, which is a dynamic lipid species. The same results were not found in Mono–Di, which are more inert. HRT may be helpful to preserve FA profile in visceral fat, but possibly not wholly sufficient in reverting the metabolic effects induced by menopause.

Solvent-Loaded Microspheres for Permeability Enhancement in Heavy Crude Oil Reservoirs

2021 ◽  
Author(s):  
Cengiz Yegin ◽  
Cenk Temizel ◽  
Mustafa Akbulut
Keyword(s):  
Energy Demand ◽  
Fossil Fuels ◽  
Analytical Techniques ◽  
Recovery Factor ◽  
Low Permeability ◽  
Sand Column ◽  
Permeability Enhancement ◽  
Recovery Potential ◽  
Novel Approach ◽  
Vis Spectroscopy

ABSTRACT With their abundancy and high-quality, it is predicted that fossil fuels will remain as the main resource that will meet the global energy demand in the several upcoming decades. Developments in hydrocarbon recovery technologies, both from conventional and unconventional reservoirs, have substantially contributed to the overall production levels in recent years. However, recovery factors obtained by using the current methods are still considered to be insufficient, and the companies have been looking for new materials and methods to enhance the efficiency and amount of recovery. One of the major issues related to low recovery factors is low permeability of reservoirs. Existence of blockages in pore throats and high level of heterogeneity lowers the mobility of hydrocarbons. In this study, we discuss development of an innovative material to be used as an additive in reservoir injection fluids to remove pore blockages in order to enhance the recovery levels. This additive material is made of pressure-sensitive microspheres loaded with solvents, which can (i) easily disperse in the injection fluid and travel to the low-permeability regions, (ii) break under pressure and confinement to release solvents, and (iii) remove blockages by targeting surroundings, especially asphalt-based particles and grains. This approach relies on the breakage of microcapsules in the confined region and release of the solvents to target blockages in porous media. In other words, the developed microspheres improve permeability of reservoirs as a result of pressure- and confinement-dependent breakage and release of solvents. Preparation of these microspheres was achieved by the encapsulation of solvent (toluene) emulsions in silica-based solid shells. Structure and stability of the solvent-loaded microspheres were examined using a variety of analytical techniques including UV-vis spectroscopy, optical microscopy, scanning electron microscope (SEM) and dynamic light scattering (DLS). It was found that the prepared microspheres possessed smooth surfaces with shell thicknesses in the range of 100-150 nm. Additionally, sand column tests were performed to evaluate the recovery potential of injection fluids in presence of solvent-loaded microspheres. It was shown that the use of solvent encapsulated in microspheres doubled the recovery factor of heavy oil compared to that of free solvent dispersed in the injection fluid. Such enhancement in the recovery factor was related to the release of solvents in localized areas, i.e., confined regions, as a consequence of breakage of microspheres. This novel approach of delivering solvents to low-permeability regions provides a significant driving force to eliminate pore blockages to facilitate mobilization of hydrocarbons trapped in confined spaces.

scholarly journals Non-invasive stimulation of vagal afferents reduces gastric frequency

2019 ◽  
Author(s):  
Vanessa Teckentrup ◽  
Sandra Neubert ◽  
João C. P. Santiago ◽  
Manfred Hallschmid ◽  
Martin Walter ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Vagus Nerve ◽  
Energy Homeostasis ◽  
Resting Energy Expenditure ◽  
Vagal Afferents ◽  
Metabolic Effects ◽  
Net Energy ◽  
Non Invasive ◽  
Induced Changes ◽  
Stimulation Of

AbstractMetabolic feedback between the gut and the brain relayed via the vagus nerve contributes to energy homeostasis. We investigated in healthy adults whether non-invasive stimulation of vagal afferents impacts energy homeostasis via efferent effects on metabolism or digestion. In a randomized crossover design, we applied transcutaneous auricular vagus nerve stimulation (taVNS) while recording efferent metabolic effects using simultaneous electrogastrography (EGG) and indirect calorimetry. We found that taVNS reduced gastric myoelectric frequency (p =.008), but did not alter resting energy expenditure. We conclude that stimulating vagal afferents induces gastric slowing via vagal efferents without acutely affecting net energy expenditure at rest. Collectively, this highlights the potential of taVNS to modulate digestion by activating the dorsal vagal complex. Thus, taVNS-induced changes in gastric frequency are an important peripheral marker of brain stimulation effects.

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