Toxicological effects of cationic nanobubbles on the liver and kidneys: biomarkers for predicting the risk.
Nanobubbles with acoustical activity are used as both diagnostic and therapeutic carriers for detecting and treating diseases. We aimed to prepare nanobubbles and assess toxic responses to them in the liver and kidneys. The cytotoxicity of nanobubbles was determined by examining the viability of liver (HepG2) and kidney (293T) cell lines after a 24-h treatment at various concentrations (0.01-2%). Toxic effects of different formulations were compared by determining functional markers such as γ-glutamyl transferase (γ-GT) and blood urea nitrogen (BUN) after intravenous administration of nanobubbles. Cationic nanobubbles caused concentration-dependent cytotoxicity against cultured cells with a more significant effect in the liver than in the kidneys. A significant reduction of viability was revealed at a concentration as low as 0.1%. Cational systems with soyaethyl morpholinium ethosulfate (SME) exhibited the greatest γ-GT level at 6-fold higher than the control. Immunohistochemistry detected liver fibrosis and inflammation with nanobubbles treatment, especially SME-containing ones at higher doses. According to plasma proteomic profiles, gelsolin and fetuin-B were significantly downregulated 3-fold in the high-dose SME-treated group. Transthyretin decreased by 6-fold in this group. The fibrinogen gamma chain expression was highly elevated. The results suggest that these protein biomarkers are sensitive for assessing the risk of nanobubble exposure. This study is the first to systematically evaluate the possible toxicity of nanobubbles in the liver and kidneys.
School of Traditional Chinese Medicine, Chang Gung University, Kweishan, Taoyuan, Taiwan.
Tai-Long
TL
Pan
Pei-Wen
PW
Wang
Saleh A
SA
Al-Suwayeh
Yi-Ju
YJ
Huang
Jia-You
JY
Fang
D000818:Animals; D015415:Biomarkers / Q000032:analysis*; D001806:Blood Urea Nitrogen; D002412:Cations; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D060752:Fetuin-B / Q000032:analysis; D005355:Fibrosis / Q000139:chemically induced; D018260:Gelsolin / Q000097:blood; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D007677:Kidney Function Tests; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000473:pathology; D008111:Liver Function Tests; D008297:Male; D009025:Morpholines / Q000633:toxicity; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D010316:Particle Size; D011228:Prealbumin / Q000032:analysis; D000644:Quaternary Ammonium Compounds / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012307:Risk Factors; D018675:Toxicity Tests; D005723:gamma-Glutamyltransferase
D015415:Biomarkers; D002412:Cations; D060752:Fetuin-B; D018260:Gelsolin; D009025:Morpholines; D011228:Prealbumin; D000644:Quaternary Ammonium Compounds; C000612979:soyaethyl morpholinium; D005723:gamma-Glutamyltransferase