In vivo protective effects of nootkatone against particles-induced lung injury caused by diesel exhaust is mediated via the Nf-κB pathway

Abderrahim Nemmar, Suhail Al-Salam, Sumaya Beegam, Priya Yuvaraju, Naserddine Hamadi, Badreldin H. Ali

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported so far. In this study we evaluated the possible protective effects of nootkatone on diesel exhaust particles (DEP)-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t.) instilled with either DEP (30 µg/mouse) or saline (control). Nootkatone was given to mice by gavage, 1 h before i.t. instillation, with either DEP or saline. Twenty-four hours following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment significantly prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated macrophage and neutrophil infiltration in the lung interstitium, assessed by histolopathology. Moreover, DEP caused a significant increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all significantly alleviated by nootkatone pretreatment. Similarly, nootkatone prevented DEP-induced DNA damage and prevented the proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-κB) induced by DEP. We conclude that nootkatone prevented the DEP-induced increase in airway resistance, lung inflammation, oxidative stress, and the subsequent DNA damage and apoptosis through a mechanism involving inhibition of NF-κB activation. Nootkatone could possibly be considered a beneficial protective agent against air pollution-induced respiratory adverse effects.

Original languageEnglish
Article number263
JournalNutrients
Volume10
Issue number3
DOIs
Publication statusPublished - Mar 1 2018

Fingerprint

nootkatone
Vehicle Emissions
Lung Injury
protective effect
lungs
Lung
transcription factor NF-kappa B
8-epi-prostaglandin F2alpha
Airway Resistance
Neutrophil Infiltration
Air Pollution
air pollution
DNA damage
DNA Damage
neutrophils
Pneumonia
mice
Oxidative Stress
oxidative stress
pretreatment

Keywords

  • Airway resistance
  • Diesel exhaust particles
  • Inflammation
  • Lung
  • NF-κB
  • Nootkatone
  • Oxidative stress

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

Cite this

In vivo protective effects of nootkatone against particles-induced lung injury caused by diesel exhaust is mediated via the Nf-κB pathway. / Nemmar, Abderrahim; Al-Salam, Suhail; Beegam, Sumaya; Yuvaraju, Priya; Hamadi, Naserddine; Ali, Badreldin H.

In: Nutrients, Vol. 10, No. 3, 263, 01.03.2018.

Research output: Contribution to journalArticle

Nemmar, Abderrahim ; Al-Salam, Suhail ; Beegam, Sumaya ; Yuvaraju, Priya ; Hamadi, Naserddine ; Ali, Badreldin H. / In vivo protective effects of nootkatone against particles-induced lung injury caused by diesel exhaust is mediated via the Nf-κB pathway. In: Nutrients. 2018 ; Vol. 10, No. 3.
@article{359d2a684c414732a7a36d4afd690b32,
title = "In vivo protective effects of nootkatone against particles-induced lung injury caused by diesel exhaust is mediated via the Nf-κB pathway",
abstract = "Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported so far. In this study we evaluated the possible protective effects of nootkatone on diesel exhaust particles (DEP)-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t.) instilled with either DEP (30 µg/mouse) or saline (control). Nootkatone was given to mice by gavage, 1 h before i.t. instillation, with either DEP or saline. Twenty-four hours following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment significantly prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated macrophage and neutrophil infiltration in the lung interstitium, assessed by histolopathology. Moreover, DEP caused a significant increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all significantly alleviated by nootkatone pretreatment. Similarly, nootkatone prevented DEP-induced DNA damage and prevented the proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-κB) induced by DEP. We conclude that nootkatone prevented the DEP-induced increase in airway resistance, lung inflammation, oxidative stress, and the subsequent DNA damage and apoptosis through a mechanism involving inhibition of NF-κB activation. Nootkatone could possibly be considered a beneficial protective agent against air pollution-induced respiratory adverse effects.",
keywords = "Airway resistance, Diesel exhaust particles, Inflammation, Lung, NF-κB, Nootkatone, Oxidative stress",
author = "Abderrahim Nemmar and Suhail Al-Salam and Sumaya Beegam and Priya Yuvaraju and Naserddine Hamadi and Ali, {Badreldin H.}",
year = "2018",
month = "3",
day = "1",
doi = "10.3390/nu10030263",
language = "English",
volume = "10",
journal = "Nutrients",
issn = "2072-6643",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "3",

}

TY - JOUR

T1 - In vivo protective effects of nootkatone against particles-induced lung injury caused by diesel exhaust is mediated via the Nf-κB pathway

AU - Nemmar, Abderrahim

AU - Al-Salam, Suhail

AU - Beegam, Sumaya

AU - Yuvaraju, Priya

AU - Hamadi, Naserddine

AU - Ali, Badreldin H.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported so far. In this study we evaluated the possible protective effects of nootkatone on diesel exhaust particles (DEP)-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t.) instilled with either DEP (30 µg/mouse) or saline (control). Nootkatone was given to mice by gavage, 1 h before i.t. instillation, with either DEP or saline. Twenty-four hours following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment significantly prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated macrophage and neutrophil infiltration in the lung interstitium, assessed by histolopathology. Moreover, DEP caused a significant increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all significantly alleviated by nootkatone pretreatment. Similarly, nootkatone prevented DEP-induced DNA damage and prevented the proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-κB) induced by DEP. We conclude that nootkatone prevented the DEP-induced increase in airway resistance, lung inflammation, oxidative stress, and the subsequent DNA damage and apoptosis through a mechanism involving inhibition of NF-κB activation. Nootkatone could possibly be considered a beneficial protective agent against air pollution-induced respiratory adverse effects.

AB - Numerous studies have shown that acute particulate air pollution exposure is linked with pulmonary adverse effects, including alterations of pulmonary function, inflammation, and oxidative stress. Nootkatone, a constituent of grapefruit, has antioxidant and anti-inflammatory effects. However, the effect of nootkatone on lung toxicity has not been reported so far. In this study we evaluated the possible protective effects of nootkatone on diesel exhaust particles (DEP)-induced lung toxicity, and the possible mechanisms underlying these effects. Mice were intratracheally (i.t.) instilled with either DEP (30 µg/mouse) or saline (control). Nootkatone was given to mice by gavage, 1 h before i.t. instillation, with either DEP or saline. Twenty-four hours following DEP exposure, several physiological and biochemical endpoints were assessed. Nootkatone pretreatment significantly prevented the DEP-induced increase in airway resistance in vivo, decreased neutrophil infiltration in bronchoalveolar lavage fluid, and abated macrophage and neutrophil infiltration in the lung interstitium, assessed by histolopathology. Moreover, DEP caused a significant increase in lung concentrations of 8-isoprostane and tumor necrosis factor α, and decreased the reduced glutathione concentration and total nitric oxide activity. These actions were all significantly alleviated by nootkatone pretreatment. Similarly, nootkatone prevented DEP-induced DNA damage and prevented the proteolytic cleavage of caspase-3. Moreover, nootkatone inhibited nuclear factor-kappaB (NF-κB) induced by DEP. We conclude that nootkatone prevented the DEP-induced increase in airway resistance, lung inflammation, oxidative stress, and the subsequent DNA damage and apoptosis through a mechanism involving inhibition of NF-κB activation. Nootkatone could possibly be considered a beneficial protective agent against air pollution-induced respiratory adverse effects.

KW - Airway resistance

KW - Diesel exhaust particles

KW - Inflammation

KW - Lung

KW - NF-κB

KW - Nootkatone

KW - Oxidative stress

UR - http://www.scopus.com/inward/record.url?scp=85042678237&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042678237&partnerID=8YFLogxK

U2 - 10.3390/nu10030263

DO - 10.3390/nu10030263

M3 - Article

VL - 10

JO - Nutrients

JF - Nutrients

SN - 2072-6643

IS - 3

M1 - 263

ER -