Pulmonary responses to polyhydroxylated fullerenols, C(60)(OH)(x).
Although many scientists have been attracted by polyhydroxylated fullerenols for their radical-scavenging and antioxidant ability in vivo and in vitro and their potential use as a drug or for drug delivery, there is little information on their pulmonary toxicological properties. The aim of this study was to investigate the effect of polyhydroxylated derivatives of fullerene on Sprague-Dawley rats after intratracheal instillation. Polyhydroxylated fullerenols [C(60)(OH)(x), x = 22, 24] were administered intratracheally (1, 5 or 10 mg per rat). Following 3-day exposures, the lungs of the rats were assessed using bronchoalveolar lavage fluid biomarkers and a pathological evaluation of lung tissue. Exposures to 1 mg per rat did not induce adverse pulmonary toxicity, while the two other doses induced cell injury effect, oxidative/nitrosative stress and inflammation, showing that C(60)(OH)(x) produced responses in a dose-dependent manner. The dosage of C(60)(OH)(x) retained in lung and the ensuing aggregation might be the main factor in the process. Our results might shed light on the possible use of C(60)(OH)(x) as an inhaled drug.
Xu
Jing-Ying
JY
Laboratory of Clinical Visual Sciences of Tongji Eye Institute and Department of Regenerative medicine, Tongji University School of Medicine, Shanghai, People's Republic of China.
Han
Kaiyu
K
Li
Shu-Xia
SX
Cheng
Jin-Sheng
JS
Xu
Guo-Tong
GT
Li
Wen-Xin
WX
Li
Qing-Nuan
QN
D000280:Administration, Inhalation; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D037741:Fullerenes / Q000009:adverse effects / Q000494:pharmacology; D006900:Hydroxylation; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010316:Particle Size; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D015415:Biomarkers; D037741:Fullerenes; C108127:fullerenol