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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

Pulmonary toxicity of soluble and solid PM components as determined by recovery of cells in BALF. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, and Zn (zinc sulfate). Note that 8-week–exposed rats received double the dose of each PM components given to those exposed for 16-weeks. Values represent mean ± SE (n = 7–8 rats per group). Horizontal line indicates control levels. *p ≤ 0.05 compared with saline control. Within-group comparison indicated significant differences (p ≤ 0.05) at 8 weeks: PM-HD vs. PM-LD; PM-HD vs. PM-L; PM-HD vs. MSH; PM-HD vs. Zn; Zn vs. PM-LD; MSH vs. PM-LD; MSH vs. PM-L and PM-L vs. PM-LD; and at 16 weeks: PM-HD vs. PM-LD, PM-HD vs. PM-L; PM-HD vs. Zn; PM-HD vs. MSH; MSH vs. PM-L; and MSH vs. Zn.
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f1-ehp0116-000013: Pulmonary toxicity of soluble and solid PM components as determined by recovery of cells in BALF. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, and Zn (zinc sulfate). Note that 8-week–exposed rats received double the dose of each PM components given to those exposed for 16-weeks. Values represent mean ± SE (n = 7–8 rats per group). Horizontal line indicates control levels. *p ≤ 0.05 compared with saline control. Within-group comparison indicated significant differences (p ≤ 0.05) at 8 weeks: PM-HD vs. PM-LD; PM-HD vs. PM-L; PM-HD vs. MSH; PM-HD vs. Zn; Zn vs. PM-LD; MSH vs. PM-LD; MSH vs. PM-L and PM-L vs. PM-LD; and at 16 weeks: PM-HD vs. PM-LD, PM-HD vs. PM-L; PM-HD vs. Zn; PM-HD vs. MSH; MSH vs. PM-L; and MSH vs. Zn.

Mentions: Chronic pulmonary inflammation can influence cardiac physiology. To determine the extent of pulmonary inflammation in each exposed group, we analyzed BALF total cells. Weekly instillations of MSH, PM suspensions (PM-HD and PM-LD), PM-L, and zinc all caused an increase in BALF total cells (Figure 1). The inflammation caused by PM-HD at 8 or 16 weeks was greatest. Exposure to soluble metal-free MSH also increased BALF cells significantly but to a lesser extent than PM-HD. The degree of inflammation was greater in all the 8-week time points postintratracheal challenges compared with the 16-week time point. This was expected, as the 16-week animals received half the concentration of each PM components on a weekly basis compared with the 8-week rats. Although the increases in total cells were apparent at 16 weeks in PM-LD, PM-L, and zinc-exposed rats, the increases were not statistically significant.


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)

Pulmonary toxicity of soluble and solid PM components as determined by recovery of cells in BALF. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, and Zn (zinc sulfate). Note that 8-week–exposed rats received double the dose of each PM components given to those exposed for 16-weeks. Values represent mean ± SE (n = 7–8 rats per group). Horizontal line indicates control levels. *p ≤ 0.05 compared with saline control. Within-group comparison indicated significant differences (p ≤ 0.05) at 8 weeks: PM-HD vs. PM-LD; PM-HD vs. PM-L; PM-HD vs. MSH; PM-HD vs. Zn; Zn vs. PM-LD; MSH vs. PM-LD; MSH vs. PM-L and PM-L vs. PM-LD; and at 16 weeks: PM-HD vs. PM-LD, PM-HD vs. PM-L; PM-HD vs. Zn; PM-HD vs. MSH; MSH vs. PM-L; and MSH vs. Zn.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f1-ehp0116-000013: Pulmonary toxicity of soluble and solid PM components as determined by recovery of cells in BALF. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, and Zn (zinc sulfate). Note that 8-week–exposed rats received double the dose of each PM components given to those exposed for 16-weeks. Values represent mean ± SE (n = 7–8 rats per group). Horizontal line indicates control levels. *p ≤ 0.05 compared with saline control. Within-group comparison indicated significant differences (p ≤ 0.05) at 8 weeks: PM-HD vs. PM-LD; PM-HD vs. PM-L; PM-HD vs. MSH; PM-HD vs. Zn; Zn vs. PM-LD; MSH vs. PM-LD; MSH vs. PM-L and PM-L vs. PM-LD; and at 16 weeks: PM-HD vs. PM-LD, PM-HD vs. PM-L; PM-HD vs. Zn; PM-HD vs. MSH; MSH vs. PM-L; and MSH vs. Zn.
Mentions: Chronic pulmonary inflammation can influence cardiac physiology. To determine the extent of pulmonary inflammation in each exposed group, we analyzed BALF total cells. Weekly instillations of MSH, PM suspensions (PM-HD and PM-LD), PM-L, and zinc all caused an increase in BALF total cells (Figure 1). The inflammation caused by PM-HD at 8 or 16 weeks was greatest. Exposure to soluble metal-free MSH also increased BALF cells significantly but to a lesser extent than PM-HD. The degree of inflammation was greater in all the 8-week time points postintratracheal challenges compared with the 16-week time point. This was expected, as the 16-week animals received half the concentration of each PM components on a weekly basis compared with the 8-week rats. Although the increases in total cells were apparent at 16 weeks in PM-LD, PM-L, and zinc-exposed rats, the increases were not statistically significant.

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