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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

Semiquantitative grading of the extent of lesions within myocardium of rats exposed to different PM fractions. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, PM, and Zn. Pathology severity scores: 0 = none, 1 = minimal, 2 = moderate, 3 = marked, and 4 = severe lesions were employed. Mean severity of lesions was calculated by adding the severity score for all animals within the group and then dividing by total number of animals. Values represent mean ± SE (n = 7–8 rats per group). *p ≤ 0.05 compared with saline control.
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f3-ehp0116-000013: Semiquantitative grading of the extent of lesions within myocardium of rats exposed to different PM fractions. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, PM, and Zn. Pathology severity scores: 0 = none, 1 = minimal, 2 = moderate, 3 = marked, and 4 = severe lesions were employed. Mean severity of lesions was calculated by adding the severity score for all animals within the group and then dividing by total number of animals. Values represent mean ± SE (n = 7–8 rats per group). *p ≤ 0.05 compared with saline control.

Mentions: In the present study the lesions were characterized by foci of myocardial degeneration, inflammation, and fibrosis. These foci were randomly distributed although frequently found at subepicardial or epicardial locations (Figure 2). A careful evaluation of serial sections of myocardial tissues demonstrated no lesions in saline controls at 8 weeks, but two of seven control animals showed mild myocardial degeneration and inflammation at 16 weeks. The photomicrographs for all 16-week exposure groups are depicted in the Supplemental Material, Figure 1 (http://www.ehponline.org/members/2007/10379/suppl.pdf). Generally, exposure of rats to MSH, PM-HD and PM-LD, PM-L, and zinc sulfate all caused small increases in lesion severity relative to saline controls at both time points. The lesion severity was statistically significant in 8-week rats exposed to MSH or PM-HD suspension (Figure 3). However, because of the low incidence of lesions in control rats at 16 weeks, the differences between groups were not statistically significant. Also, because of the limited group size (n = 8 for all groups), statistical significance could not be reached across the exposure regimens. Careful evaluation of the location of the lesions in each exposure group revealed no clear distributional differences between groups. Thus, on the basis of a histopathologic evaluation, it was difficult for us to identify the difference in lesion severity between different exposure conditions.


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)

Semiquantitative grading of the extent of lesions within myocardium of rats exposed to different PM fractions. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, PM, and Zn. Pathology severity scores: 0 = none, 1 = minimal, 2 = moderate, 3 = marked, and 4 = severe lesions were employed. Mean severity of lesions was calculated by adding the severity score for all animals within the group and then dividing by total number of animals. Values represent mean ± SE (n = 7–8 rats per group). *p ≤ 0.05 compared with saline control.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f3-ehp0116-000013: Semiquantitative grading of the extent of lesions within myocardium of rats exposed to different PM fractions. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, PM, and Zn. Pathology severity scores: 0 = none, 1 = minimal, 2 = moderate, 3 = marked, and 4 = severe lesions were employed. Mean severity of lesions was calculated by adding the severity score for all animals within the group and then dividing by total number of animals. Values represent mean ± SE (n = 7–8 rats per group). *p ≤ 0.05 compared with saline control.
Mentions: In the present study the lesions were characterized by foci of myocardial degeneration, inflammation, and fibrosis. These foci were randomly distributed although frequently found at subepicardial or epicardial locations (Figure 2). A careful evaluation of serial sections of myocardial tissues demonstrated no lesions in saline controls at 8 weeks, but two of seven control animals showed mild myocardial degeneration and inflammation at 16 weeks. The photomicrographs for all 16-week exposure groups are depicted in the Supplemental Material, Figure 1 (http://www.ehponline.org/members/2007/10379/suppl.pdf). Generally, exposure of rats to MSH, PM-HD and PM-LD, PM-L, and zinc sulfate all caused small increases in lesion severity relative to saline controls at both time points. The lesion severity was statistically significant in 8-week rats exposed to MSH or PM-HD suspension (Figure 3). However, because of the low incidence of lesions in control rats at 16 weeks, the differences between groups were not statistically significant. Also, because of the limited group size (n = 8 for all groups), statistical significance could not be reached across the exposure regimens. Careful evaluation of the location of the lesions in each exposure group revealed no clear distributional differences between groups. Thus, on the basis of a histopathologic evaluation, it was difficult for us to identify the difference in lesion severity between different exposure conditions.

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