Limits...
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.

Show MeSH

Related in: MedlinePlus

Cardiac mitochondrial DNA damage after eight weekly exposures to solid PM or soluble components in rats. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, and Zn. Note that because of sample-to-sample variation, the only groups that reached statistical significance are Zn and PM-HD, although the trend was consistent in other groups exposed to PM containing water-soluble zinc. Values represent mean ± SE (n = 8 rats per group). Note that control values are normalized to zero. * p ≤ 0.05 compared with saline control.
© Copyright Policy - public-domain
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2199289&req=5

f4-ehp0116-000013: Cardiac mitochondrial DNA damage after eight weekly exposures to solid PM or soluble components in rats. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, and Zn. Note that because of sample-to-sample variation, the only groups that reached statistical significance are Zn and PM-HD, although the trend was consistent in other groups exposed to PM containing water-soluble zinc. Values represent mean ± SE (n = 8 rats per group). Note that control values are normalized to zero. * p ≤ 0.05 compared with saline control.

Mentions: The mitochondrial DNA damage in left ventricular tissues from rats exposed for 8 weeks was analyzed using Q-PCR. The rationale of the Q-PCR assay is that the damage in either mitochondrial or nuclear DNA reduces the amplification efficiency of the template, leading to reduction of PCR product with the damaged template. The DNA damage is calculated as discussed in “Materials and Methods.” The results show that the rats exposed to PM-HD and zinc sulfate had significantly increased mitochondrial DNA damage compared with saline (Figure 4). Rats exposed to PM-L also indicated an increase in lesions compared with saline or PM without zinc (MSH), but it was not statistically significant. MSH did not cause mitochondrial DNA damage.


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)

Cardiac mitochondrial DNA damage after eight weekly exposures to solid PM or soluble components in rats. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, and Zn. Note that because of sample-to-sample variation, the only groups that reached statistical significance are Zn and PM-HD, although the trend was consistent in other groups exposed to PM containing water-soluble zinc. Values represent mean ± SE (n = 8 rats per group). Note that control values are normalized to zero. * 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

f4-ehp0116-000013: Cardiac mitochondrial DNA damage after eight weekly exposures to solid PM or soluble components in rats. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PM-L, and Zn. Note that because of sample-to-sample variation, the only groups that reached statistical significance are Zn and PM-HD, although the trend was consistent in other groups exposed to PM containing water-soluble zinc. Values represent mean ± SE (n = 8 rats per group). Note that control values are normalized to zero. * p ≤ 0.05 compared with saline control.
Mentions: The mitochondrial DNA damage in left ventricular tissues from rats exposed for 8 weeks was analyzed using Q-PCR. The rationale of the Q-PCR assay is that the damage in either mitochondrial or nuclear DNA reduces the amplification efficiency of the template, leading to reduction of PCR product with the damaged template. The DNA damage is calculated as discussed in “Materials and Methods.” The results show that the rats exposed to PM-HD and zinc sulfate had significantly increased mitochondrial DNA damage compared with saline (Figure 4). Rats exposed to PM-L also indicated an increase in lesions compared with saline or PM without zinc (MSH), but it was not statistically significant. MSH did not cause mitochondrial DNA damage.

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