Endothelial dysfunction in normal and prediabetic rats with metabolic syndrome exposed by oral gavage to carbon black nanoparticles

TY - JOUR

T1 - Endothelial dysfunction in normal and prediabetic rats with metabolic syndrome exposed by oral gavage to carbon black nanoparticles

AU - Folkmann, Janne Kjærsgaard

AU - Vesterdal, Lise Kristine

AU - Sheykhzade, Majid

AU - Loft, Steffen

AU - Møller, Peter

PY - 2012/9

Y1 - 2012/9

N2 - Exposure to nanosized particles may increase the risk of cardiovascular diseases by endothelial dysfunction, particularly in susceptible subjects with metabolic syndrome. We investigated vasomotor dysfunction in aorta from obese and lean Zucker rats after oral exposure to nanosized carbon black (CB). Rats were exposed to 1 or 10 weekly doses of 0, 0.064, 0.64 or 6.4mg/kg bodyweight and sacrificed 24h or 13 weeks later. The exposure to 10 doses of 0.064 or 0.64mg/kg reduced the acetylcholine-induced vasorelaxation in the lean and obese rats. The half maximal effect concentration values increased by twofold (95% CI: 1.1-3.5-fold) and fourfold (95% CI: 2.3-6.9-fold) in the rats exposed to 0.064 and 0.64mg/kg compared with the controls, respectively. The rats exposed to 10 doses of 0.64mg/kg had also 20% (95% CI: 10-29%) lower maximal effect value compared with the controls. However, the nitroglycerin-induced vasorelaxation and phenylephrine-induced vasocontraction was not affected in rats exposed to CB. The endothelial dysfunction was not observed in rats sacrificed 13 weeks after the last CB exposure. There was unaltered expression of Chrm3, Nos3, Nos2, Ccl2, and Hmox1 in aorta tissue of CB-exposed rats. In conclusion, repeated oral exposure to CB was associated with endothelial dysfunction in rats, further aggravating the effect of metabolic syndrome.

AB - Exposure to nanosized particles may increase the risk of cardiovascular diseases by endothelial dysfunction, particularly in susceptible subjects with metabolic syndrome. We investigated vasomotor dysfunction in aorta from obese and lean Zucker rats after oral exposure to nanosized carbon black (CB). Rats were exposed to 1 or 10 weekly doses of 0, 0.064, 0.64 or 6.4mg/kg bodyweight and sacrificed 24h or 13 weeks later. The exposure to 10 doses of 0.064 or 0.64mg/kg reduced the acetylcholine-induced vasorelaxation in the lean and obese rats. The half maximal effect concentration values increased by twofold (95% CI: 1.1-3.5-fold) and fourfold (95% CI: 2.3-6.9-fold) in the rats exposed to 0.064 and 0.64mg/kg compared with the controls, respectively. The rats exposed to 10 doses of 0.64mg/kg had also 20% (95% CI: 10-29%) lower maximal effect value compared with the controls. However, the nitroglycerin-induced vasorelaxation and phenylephrine-induced vasocontraction was not affected in rats exposed to CB. The endothelial dysfunction was not observed in rats sacrificed 13 weeks after the last CB exposure. There was unaltered expression of Chrm3, Nos3, Nos2, Ccl2, and Hmox1 in aorta tissue of CB-exposed rats. In conclusion, repeated oral exposure to CB was associated with endothelial dysfunction in rats, further aggravating the effect of metabolic syndrome.

U2 - 10.1093/toxsci/kfs180

DO - 10.1093/toxsci/kfs180

M3 - Journal article

C2 - 22610611

SN - 1096-6080

VL - 129

SP - 98

EP - 107

JO - Toxicological Sciences

JF - Toxicological Sciences

IS - 1

ER -