Background: Caloric restriction (CR) is known to improve health and extend life span in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.
Results: Male C57BL/6J mice were fed with CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m³) of PM 2.5. Compared to AL-fed mice, CR-fed mice attenuated PM-induced pulmonary injury and systemic toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. Analysis of RNA sequencing revealed that several pulmonary pathways involved in production of ROS, cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay.
Conclusion: These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and systemic toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.
Keywords: Caloric restriction, particulate matter, pulmonary injury, systemic effects, RNA sequencing, xenobiotic metabolism.
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Received 15 May, 2020
Received 15 May, 2020
On 14 May, 2020
On 13 May, 2020
Invitations sent on 13 May, 2020
On 13 May, 2020
On 13 May, 2020
On 12 May, 2020
On 12 May, 2020
Posted 10 Feb, 2020
On 06 Apr, 2020
Received 25 Mar, 2020
On 20 Mar, 2020
Received 12 Mar, 2020
Received 12 Mar, 2020
On 10 Mar, 2020
On 10 Mar, 2020
Invitations sent on 09 Mar, 2020
On 06 Feb, 2020
On 05 Feb, 2020
On 05 Feb, 2020
On 05 Feb, 2020
Received 15 May, 2020
Received 15 May, 2020
On 14 May, 2020
On 13 May, 2020
Invitations sent on 13 May, 2020
On 13 May, 2020
On 13 May, 2020
On 12 May, 2020
On 12 May, 2020
Posted 10 Feb, 2020
On 06 Apr, 2020
Received 25 Mar, 2020
On 20 Mar, 2020
Received 12 Mar, 2020
Received 12 Mar, 2020
On 10 Mar, 2020
On 10 Mar, 2020
Invitations sent on 09 Mar, 2020
On 06 Feb, 2020
On 05 Feb, 2020
On 05 Feb, 2020
On 05 Feb, 2020
Background: Caloric restriction (CR) is known to improve health and extend life span in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined.
Results: Male C57BL/6J mice were fed with CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m³) of PM 2.5. Compared to AL-fed mice, CR-fed mice attenuated PM-induced pulmonary injury and systemic toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. Analysis of RNA sequencing revealed that several pulmonary pathways involved in production of ROS, cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay.
Conclusion: These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and systemic toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.
Keywords: Caloric restriction, particulate matter, pulmonary injury, systemic effects, RNA sequencing, xenobiotic metabolism.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
This is a list of supplementary files associated with this preprint. Click to download.
Loading...