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

Abstract

A comprehensive distribution study was conducted in female rats and mice exposed to a suspension of uniformly carbon-14 labeled C60 ([14C(U)]C60). Rodents were administered [14C(U)]C60 (~0.9 mg /kg body weight) or 5% PVP-saline vehicle alone via a single tail vein injection. Tissues were collected at 1 hour, 1, 7, 14 and 30 days after administration. A separate group of rodents received 5 daily injections of suspensions of either [14C(U)]C60 or vehicle with tissue collection 14 days post exposure. Radioactivity was detected in over 20 tissues at all time period. The highest concentration of radioactivity in rodents at each time point was in liver, lungs and spleen. Elimination of [14C(U)]C60 was <2% in urine and feces at any 24 hour time points. [14C(U)]C60 and [14C(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 post exposure, respectively. The blood radioactivity at 1 hour after [14C(U)]C60 exposure was four-fold higher in rats than in mice; blood radioactivity was still in circulation at 30 days post [14C(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 vWF, increased in rats, but remained at control levels in mice. This study demonstrates that [14C(U)]C60 is retained in female rodents with little elimination by 30 days after i.v. exposure, and leads to systemic oxidative stress.

Distribution and biomarker of carbon‐14 labeled fullerene C60 ([14C(U)]C60) in pregnant and lactating rats and their offspring after maternal intravenous exposure

“…Comparison of the current distribution data with an earlier study of the distribution of [ 14 C(U)]C 60 formulated as a 5% PVP suspension in saline in non-pregnant female rats (Sumner, et al 2015), showed that lung distribution of radioactivity at 24 hours post exposure was similar in non-pregnant rats and lactating rats (17% and 11%, respectively), but was much higher in pregnant dams (24% for GD11–24h, 41% for GD15–24h and 42% for GD18–24h). The percentage of recovered radioactivity in liver at 24 hours after exposure in non-pregnant rats (55%) and in lactating rats (70%) was higher than in pregnant dams regardless of GD (39% for GD11–24h, 30% for GD15–24h, and 23% for GD18–24h).…”

“…Distribution of [ 14 C(U)]C 60 in non-pregnant female rats and mice showed that radioactivity were detectable in over 20 tissues at 30 days post a single i.v. dose (Sumner, et al 2015). The results presented here showed a maternal-fetal transfer of [ 14 C(U)]C 60 at all gestational phases, and a continuous transfer via milk to the pups over 11 days.…”

“…Following the protocol from our previous published work (Sumner, et al 2015), [ 14 C(U)]C 60 was prepared using the Kratschmer and co-workers (Kratschmer, et al 1990) plasma arc discharge method as modified by Scrivens and Tour (Scrivens, et al 1994). [ 14 C(U)]C 60 was isolated by exhaustive extraction of the soot with toluene, followed by column chromatography on alumina, eluting with hexane.…”

“…Characterization of the dosing solution was done as previously described (Sumner, et al 2015). Briefly, the suspensions, were analyzed for hydrodynamic diameter using a Malvern Zetasizer NanoZS (Malvern Instruments, Worcestershire, UK) with a 633 nm laser source, 173° detection angle.…”

“…Metabolomics analysis was conducted as previously described (Church, et al 2014, Pathmasiri, et al 2012, Sumner, et al 2009, Sumner, et al 2010a, Sumner, et al 2015, Sumner, et al 2010f). Briefly, NMR data were processed by automated integration (increments of 0.04 ppm) over the spectral window (binning, using ACD 1D NMR Processor 12.0, ACD Labs, Torronto, Canada), excluding the region of water suppression, urea, and the DSS signal and each of the bins was normalized to the total integral of the bins of each spectrum.…”