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 tissue total aconitase activity in rats exposed to soluble or solid PM components for 8 or 16 weeks. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PL-L, and Zn. Zinc concentration in PM-HD, and PM-L and Zn groups is the same. Note that rats received the same dose of PM or other components for 8 and 16 weeks. Values represent mean ± SE (n = 8 rats per group). *p ≤ 0.05 compared with saline control.
© Copyright Policy - public-domain
Related In: Results  -  Collection

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

f5-ehp0116-000013: Cardiac tissue total aconitase activity in rats exposed to soluble or solid PM components for 8 or 16 weeks. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PL-L, and Zn. Zinc concentration in PM-HD, and PM-L and Zn groups is the same. Note that rats received the same dose of PM or other components for 8 and 16 weeks. Values represent mean ± SE (n = 8 rats per group). *p ≤ 0.05 compared with saline control.

Mentions: Two isoforms of aconitase exist in the cell. One is cytosolic and the other is mitochondrial. The iron–sulfur clusters of both aconitase isoforms are prone to inactivation by oxidative stress (Cairo et al. 2002; Tong and Rouault 2007), and thus their activity analyses have been extensively used to demonstrate oxidative stress. We determined total aconitase activity at both time points in cardiac tissue homogenates, which included cytosolic plus mitochondrial isoform. There was a small but statistically significant inhibition of aconitase activity in rats exposed to zinc and PM-L in the 8-week group. Although a trend of inhibition was apparent, aconitase activity was not significant in other groups compared with saline (Figure 5).


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 tissue total aconitase activity in rats exposed to soluble or solid PM components for 8 or 16 weeks. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PL-L, and Zn. Zinc concentration in PM-HD, and PM-L and Zn groups is the same. Note that rats received the same dose of PM or other components for 8 and 16 weeks. Values represent mean ± SE (n = 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

f5-ehp0116-000013: Cardiac tissue total aconitase activity in rats exposed to soluble or solid PM components for 8 or 16 weeks. Group designations are as follows: saline (control), MSH, PM-HD, PM-LD, PL-L, and Zn. Zinc concentration in PM-HD, and PM-L and Zn groups is the same. Note that rats received the same dose of PM or other components for 8 and 16 weeks. Values represent mean ± SE (n = 8 rats per group). *p ≤ 0.05 compared with saline control.
Mentions: Two isoforms of aconitase exist in the cell. One is cytosolic and the other is mitochondrial. The iron–sulfur clusters of both aconitase isoforms are prone to inactivation by oxidative stress (Cairo et al. 2002; Tong and Rouault 2007), and thus their activity analyses have been extensively used to demonstrate oxidative stress. We determined total aconitase activity at both time points in cardiac tissue homogenates, which included cytosolic plus mitochondrial isoform. There was a small but statistically significant inhibition of aconitase activity in rats exposed to zinc and PM-L in the 8-week group. Although a trend of inhibition was apparent, aconitase activity was not significant in other groups compared with saline (Figure 5).

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