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Nanoparticle-induced oxidative stress and cardiovascular effects assessed by animal models


Janne Kjærsgaard Folkmann


Oxidative stress induced DNA damage because the activity of oxoguanine DNA glycolylase 1(OGG1) was mainly unaltered in the liver and lungs of nanoparticle exposed rats.The second study focused on the vascular function caused by oral exposure to one or repeateddoses of nanosized CB particles. Normal and prediabetic rats with metabolic syndrome wereexposed to CB by oral gavage to either one (0.064, 0.64, or 6.4 mg/kg bw), or repeated doses(0.064 or 0.64 mg/kg bw once a week for 10 weeks) and killed 24 hours or 13 weeks later. Thevasomotor function was assessed in the segments of the aorta, mounted in myographs. Themicrovascular function was assessed in segments of second-order mesenteric arteries mounted ina pressure myograph, supplemented by an ex vivo exposure study of mesenteric arteries to CB.The prediabetic rats displayed altered vasomotor function in aorta segments related to increasedvasoconstriction and reduced vasodilatation which to some extent was dependent on the age ofanimal. Rats exposed to 10 doses of CB displayed endothelial dysfunction in the aorta,evidenced by reduced responsiveness to acetylcholine-mediated vasorelaxation in terms of lowerEmax and right-shift of EC50-values. Endothelium-independent vasorelaxation or phenylephrineinducedvasocontraction in aorta segments was not affected in rats exposed to CB. Single doseexposures did not alter the vasomotor function in aorta and there was no dysfunction in ratskilled 13 weeks after the last administration. The microvascular function in mesenteric arterieswas determined as acetylcholine-dependent vasorelaxation of pressurized vessels and as externalvessel diameter in reponse to increased intraluminal pressure. The normal and prediabetic ratswere not affected by single or repeated doses of CB in terms of acetylcholine-dependentvasorelaxation or external diameter of pressurized vessels. Treatment of the pressurizedmesenteric vessels ex vivo with 10 μg/ml of CB resulted in decreased external diameter whenincreasing the intraluminal pressure, whereas the acetylcholine-induced vasorelaxation wasunaltered.In conclusion, oral exposure to carbon-based nanoparticles causes oxidative stress andendothelial dysfunction in animal models. Oral exposure to C60 fullerenes or SWCNT generatesoxidized DNA in liver and lungs. C60 fullerenes dissolved in saline also influence theexpression of repair genes mRNA in the liver. Furthermore, oral exposure to nanosized CBproduced endothelial dysfunction in aorta from rats with and without metabolic syndrome,whereas the microvascular function was unaffected.