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.

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.

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

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.

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.

Direct metabolic effects of isoproterenol and propranolol in ischemic myocardium of the dog

1980 ◽  
Vol 239 (4) ◽  
pp. H469-H469
Author(s):  
Michael Goodlett ◽  
Kyran Dowling ◽  
Lynne J. Eddy ◽  
James M. Downey
Keyword(s):  
High Energy ◽  
Ischemic Myocardium ◽  
The Other ◽  
Energy Utilization ◽  
Metabolic Effects ◽  
Low Flow ◽  
High Energy Phosphate ◽  
Drug Induced ◽  
Flow Rates ◽  
Induced Changes

The effect of either isoproterenol or propranolol on the metabolism of ischemic myocardium was examined. To ensure that all changes were due to changes in metabolism and not drug-induced changes in residual flow to the ischemic regions, we devised a preparation in which two coronary branches on the same heart were simultaneously perfused at a low flow rate. Microsphere measurements verified that the two ischemic regions were receiving identical blood flow rates. One branch received an infusion of 0.9% NaCl and the other received the drug. After 1 h both regions were biopsied and the high-energy phosphate levels in each region were determined. ATP and phosphocreatine each fell to about 50% of their starting values in the 0.9% NaCl-treated regions, and isoproterenol did not further depress the high-energy phosphate concentrations. Propranolol, on the other hand, significantly preserved the high-energy phosphate concentrations. We conclude that although isoproterenol seemed incapable of accelerating energy utilization in ischemic myocardium, propranolol is apparently capable of reducing it.

scholarly journals Analgesic effects of optogenetic inhibition of basolateral amygdala inputs into the prefrontal cortex in nerve injured female mice

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Vinicius M. Gadotti ◽  
Zizhen Zhang ◽  
Junting Huang ◽  
Gerald W. Zamponi
Keyword(s):  
Prefrontal Cortex ◽  
Nerve Injury ◽  
Basolateral Amygdala ◽  
Thermal Hyperalgesia ◽  
Pyramidal Cells ◽  
Male Mice ◽  
Female Mice ◽  
Analgesic Effects ◽  
Induced Changes ◽  
Thermal Stimuli

AbstractPeripheral nerve injury can lead to remodeling of brain circuits, and this can cause chronification of pain. We have recently reported that male mice subjected to spared injury of the sciatic nerve undergo changes in the function of the medial prefrontal cortex (mPFC) that culminate in reduced output of layer 5 pyramidal cells. More recently, we have shown that this is mediated by alterations in synaptic inputs from the basolateral amygdala (BLA) into GABAergic interneurons in the mPFC. Optogenetic inhibition of these inputs reversed mechanical allodynia and thermal hyperalgesia in male mice. It is known that the processing of pain signals can exhibit marked sex differences. We therefore tested whether the dysregulation of BLA to mPFC signaling is equally altered in female mice. Injection of AAV-Arch3.0 constructs into the BLA followed by implantation of a fiberoptic cannula into the mPFC in sham and SNI operated female mice was carried out, and pain behavioral responses were measured in response to yellow light mediated activation of this inhibitory opsin. Our data reveal that Arch3.0 activation leads to a marked increase in paw withdrawal thresholds and latencies in response to mechanical and thermal stimuli, respectively. However, we did not observe nerve injury-induced changes in mPFC layer 5 pyramidal cell output in female mice. Hence, the observed light-induced analgesic effects may be due to compensation for dysregulated neuronal circuits downstream of the mPFC.

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