Distribution and biomarkers of carbon-14-labeled fullerene C60 ([(14) C(U)]C60 ) in female rats and mice for up to 30 days after intravenous exposure.
A comprehensive distribution study was conducted in female rats and mice exposed to a suspension of uniformly carbon-14-labeled C60 ([(14) C(U)]C60 ). Rodents were administered [(14) C(U)]C60 (~0.9 mg kg(-1) body weight) or 5% polyvinylpyrrolidone-saline vehicle alone via a single tail vein injection. Tissues were collected at 1 h and 1, 7, 14 and 30 days after administration. A separate group of rodents received five daily injections of suspensions of either [(14) C(U)]C60 or vehicle with tissue collection 14 days post exposure. Radioactivity was detected in over 20 tissues at all time points. The highest concentration of radioactivity in rodents at each time point was in liver, lungs and spleen. Elimination of [(14) C(U)]C60 was < 2% in urine and feces at any 24 h time points. [(14) C(U)]C60 and [(14) C(U)]C60 -retinol were detected in liver of rats and together accounted for ~99% and ~56% of the total recovered at 1 and 30 days postexposure, respectively. The blood radioactivity at 1 h after [(14) C(U)]C60 exposure was fourfold higher in rats than in mice; blood radioactivity was still in circulation at 30 days post [(14) C(U)]C60 exposure in both species (<1%). Levels of oxidative stress markers increased by 5 days after exposure and remained elevated, while levels of inflammation markers initially increased and then returned to control values. The level of cardiovascular marker von Willebrand factor, increased in rats, but remained at control levels in mice. This study demonstrates that [(14) C(U)]C60 is retained in female rodents with little elimination by 30 days after i.v. exposure, and leads to systemic oxidative stress.
Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, USA.
Susan C J
SC
Sumner
Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, USA.
Rodney W
RW
Snyder
Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
Christopher
C
Wingard
Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, USA.
Ninell P
NP
Mortensen
Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
Nathan A
NA
Holland
Department of Physiology, Brody School of Medicine, East Carolina University, Greenville, NC, USA.
Jonathan H
JH
Shannahan
Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, USA.
Suraj
S
Dhungana
Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, USA.
Wimal
W
Pathmasiri
Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, USA.
Li
L
Han
Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, USA.
Anita H
AH
Lewin
Discovery - Science - Technology, RTI International, 3040 Cornwallis Drive, Research Triangle Park, NC, USA.
Timothy R
TR
Fennell
D061605:Administration, Intravenous; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced* / Q000276:immunology / Q000652:urine; D005260:Female; D037741:Fullerenes / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity / Q000652:urine; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008657:Metabolic Clearance Rate; D055432:Metabolomics; D008810:Mice, Inbred C57BL; D009928:Organ Specificity; D018384:Oxidative Stress / Q000187:drug effects* / Q000276:immunology; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution
D015415:Biomarkers; D002250:Carbon Radioisotopes; D037741:Fullerenes; C069837:fullerene C60
Carbon-14 labeled C60 ([14C(U)]C60); In vivo disposition; cytokines; female rodents; fullerenes; metabolomics analysis; oxidative stress; species variation