Distribution and biomarkers of carbon-14-labeled fullerene C60 ([14C(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 C-60 ([C-14(U)]C-60). Rodents were administered [C-14(U)]C-60 (similar to 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 [C-14(U)]C-60 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 [C-14(U)]C-60 was < 2% in urine and feces at any 24 h time points. [C-14(U)]C-60 and [C-14(U)]C-60-retinol were detected in liver of rats and together accounted for similar to 99% and similar to 56% of the total recovered at 1 and 30 days postexposure, respectively. The blood radioactivity at 1 h after [C-14(U)]C-60 exposure was fourfold higher in rats than in mice; blood radioactivity was still in circulation at 30 days post [C-14(U)]C-60 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 [C-14(U)]C-60 is retained in female rodents with little elimination by 30 days after i.v. exposure, and leads to systemic oxidative stress. Copyright (c) 2015 John Wiley & Sons, Ltd. A comprehensive investigation of the distribution of polyvinylpyrrolidone-formulated [C-14(U)]C-60 (suspended in saline to form a 5% polyvinylpyrrolidone-saline suspension) in female rats and mice administered a single or five consecutive daily tail vein injections. Biomarkers of inflammation, cardiovascular injury and oxidative stress were measured to study the biological impact of [C-14(U)]C-60 exposure. The goals of the investigation were to provide a basic understanding of the distribution, migration, elimination and biological impacts of [C-14(U)]C-60 in rats and mice.