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The role of particulate matter-associated zinc in cardiac injury in rats.

Kodavanti UP, Schladweiler MC, Gilmour PS, Wallenborn JG, Mandavilli BS, Ledbetter AD, Christiani DC, Runge MS, Karoly ED, Costa DL, Peddada S, Jaskot R, Richards JH, Thomas R, Madamanchi NR, Nyska A - Environ. Health Perspect. (2008)

Bottom Line: We investigated the role of PM-associated zinc in cardiac injury.We analyzed mitochondrial DNA damage using quantitative polymerase chain reaction and found that all groups except MSH caused varying degrees of damage relative to control.These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.

View Article: PubMed Central - PubMed

Affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27710, USA. kodavanti.urmila@epa.gov

ABSTRACT

Background: Exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity; however, causative components are unknown. Zinc is a major element detected at high levels in urban air.

Objective: We investigated the role of PM-associated zinc in cardiac injury.

Methods: We repeatedly exposed 12- to 14-week-old male Wistar Kyoto rats intratracheally (1x/week for 8 or 16 weeks) to a) saline (control); b) PM having no soluble zinc (Mount St. Helens ash, MSH); or c) whole-combustion PM suspension containing 14.5 microg/mg of water-soluble zinc at high dose (PM-HD) and d ) low dose (PM-LD), e) the aqueous fraction of this suspension (14.5 microg/mg of soluble zinc) (PM-L), or f ) zinc sulfate (rats exposed for 8 weeks received double the concentration of all PM components of rats exposed for 16 weeks).

Results: Pulmonary inflammation was apparent in all exposure groups when compared with saline (8 weeks > 16 weeks). PM with or without zinc, or with zinc alone caused small increases in focal subepicardial inflammation, degeneration, and fibrosis. Lesions were not detected in controls at 8 weeks but were noted at 16 weeks. We analyzed mitochondrial DNA damage using quantitative polymerase chain reaction and found that all groups except MSH caused varying degrees of damage relative to control. Total cardiac aconitase activity was inhibited in rats receiving soluble zinc. Expression array analysis of heart tissue revealed modest changes in mRNA for genes involved in signaling, ion channels function, oxidative stress, mitochondrial fatty acid metabolism, and cell cycle regulation in zinc but not in MSH-exposed rats.

Conclusion: These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.

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Related in: MedlinePlus

A Venn diagram depicting differences and commonalities in number of genes expressed by given exposure condition. Differentially expressed genes for MSH, PM-HD (whole particle suspension), and zinc sulfate relative to saline were used in developing a Venn diagram. A list of genes for each distinct sections of the Venn diagram is provided in Supplemental Material, Table 5 (http://www.ehponline.org/members/2007/10379/suppl.pdf) .
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f6-ehp0116-000013: A Venn diagram depicting differences and commonalities in number of genes expressed by given exposure condition. Differentially expressed genes for MSH, PM-HD (whole particle suspension), and zinc sulfate relative to saline were used in developing a Venn diagram. A list of genes for each distinct sections of the Venn diagram is provided in Supplemental Material, Table 5 (http://www.ehponline.org/members/2007/10379/suppl.pdf) .

Mentions: To understand mechanistic differences between cardiac effects of solid PM without zinc and zinc sulfate, we performed microarray analyses of cardiac tissues from saline, MSH-, PM-HD–, and zinc sulfate–exposed rats at the 8-week time point. Unlike cardiac gene expression changes after high-dose single pulmonary exposure to zinc sulfate (Gilmour et al., 2006b), small changes in a limited number of genes were noted in the present study [Supplemental Material, Tables 1–4 (http://www.ehponline.org/members/2007/10379/suppl.pdf)]. Therefore, false discovery rate correction was not employed to minimize omission of the exposure-related changes. However, we did apply a fold change cutoff for listed genes (> 1.25 and < 0.75). A Venn diagram indicating number of genes commonly or distinctly affected by MSH, PM-HD, and zinc sulfate is given in the Figure 6. Supplemental Material, Table 5 (http://www.ehponline.org/members/2007/10379/suppl.pdf) is a list of genes for each distinct section of the Venn diagram.


The role of particulate matter-associated zinc in cardiac injury in rats.

Kodavanti UP, Schladweiler MC, Gilmour PS, Wallenborn JG, Mandavilli BS, Ledbetter AD, Christiani DC, Runge MS, Karoly ED, Costa DL, Peddada S, Jaskot R, Richards JH, Thomas R, Madamanchi NR, Nyska A - Environ. Health Perspect. (2008)

A Venn diagram depicting differences and commonalities in number of genes expressed by given exposure condition. Differentially expressed genes for MSH, PM-HD (whole particle suspension), and zinc sulfate relative to saline were used in developing a Venn diagram. A list of genes for each distinct sections of the Venn diagram is provided in Supplemental Material, Table 5 (http://www.ehponline.org/members/2007/10379/suppl.pdf) .
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2199289&req=5

f6-ehp0116-000013: A Venn diagram depicting differences and commonalities in number of genes expressed by given exposure condition. Differentially expressed genes for MSH, PM-HD (whole particle suspension), and zinc sulfate relative to saline were used in developing a Venn diagram. A list of genes for each distinct sections of the Venn diagram is provided in Supplemental Material, Table 5 (http://www.ehponline.org/members/2007/10379/suppl.pdf) .
Mentions: To understand mechanistic differences between cardiac effects of solid PM without zinc and zinc sulfate, we performed microarray analyses of cardiac tissues from saline, MSH-, PM-HD–, and zinc sulfate–exposed rats at the 8-week time point. Unlike cardiac gene expression changes after high-dose single pulmonary exposure to zinc sulfate (Gilmour et al., 2006b), small changes in a limited number of genes were noted in the present study [Supplemental Material, Tables 1–4 (http://www.ehponline.org/members/2007/10379/suppl.pdf)]. Therefore, false discovery rate correction was not employed to minimize omission of the exposure-related changes. However, we did apply a fold change cutoff for listed genes (> 1.25 and < 0.75). A Venn diagram indicating number of genes commonly or distinctly affected by MSH, PM-HD, and zinc sulfate is given in the Figure 6. Supplemental Material, Table 5 (http://www.ehponline.org/members/2007/10379/suppl.pdf) is a list of genes for each distinct section of the Venn diagram.

Bottom Line: We investigated the role of PM-associated zinc in cardiac injury.We analyzed mitochondrial DNA damage using quantitative polymerase chain reaction and found that all groups except MSH caused varying degrees of damage relative to control.These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.

View Article: PubMed Central - PubMed

Affiliation: National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27710, USA. kodavanti.urmila@epa.gov

ABSTRACT

Background: Exposure to particulate matter (PM) has been associated with increased cardiovascular morbidity; however, causative components are unknown. Zinc is a major element detected at high levels in urban air.

Objective: We investigated the role of PM-associated zinc in cardiac injury.

Methods: We repeatedly exposed 12- to 14-week-old male Wistar Kyoto rats intratracheally (1x/week for 8 or 16 weeks) to a) saline (control); b) PM having no soluble zinc (Mount St. Helens ash, MSH); or c) whole-combustion PM suspension containing 14.5 microg/mg of water-soluble zinc at high dose (PM-HD) and d ) low dose (PM-LD), e) the aqueous fraction of this suspension (14.5 microg/mg of soluble zinc) (PM-L), or f ) zinc sulfate (rats exposed for 8 weeks received double the concentration of all PM components of rats exposed for 16 weeks).

Results: Pulmonary inflammation was apparent in all exposure groups when compared with saline (8 weeks > 16 weeks). PM with or without zinc, or with zinc alone caused small increases in focal subepicardial inflammation, degeneration, and fibrosis. Lesions were not detected in controls at 8 weeks but were noted at 16 weeks. We analyzed mitochondrial DNA damage using quantitative polymerase chain reaction and found that all groups except MSH caused varying degrees of damage relative to control. Total cardiac aconitase activity was inhibited in rats receiving soluble zinc. Expression array analysis of heart tissue revealed modest changes in mRNA for genes involved in signaling, ion channels function, oxidative stress, mitochondrial fatty acid metabolism, and cell cycle regulation in zinc but not in MSH-exposed rats.

Conclusion: These results suggest that water-soluble PM-associated zinc may be one of the causal components involved in PM cardiac effects.

Show MeSH
Related in: MedlinePlus