Comparative effects of sulfhydryl compounds on target organellae, nuclei and mitochondria, of hydroxylated fullerene‐induced cytotoxicity in isolated rat hepatocytes. Issue 12 (23rd March 2015)

• Record Type: Journal Article
• Authors: Nakagawa, Yoshio; Inomata, Akiko; Ogata, Akio; Nakae, Dai
• Is Part Of: Journal of applied toxicology. Volume 35:Issue 12(2015)
• Page Start: 1465
• Page End: 1472
• Publication Date: 2015-03-23
• Subjects: Toxicology -- Periodicals; Industrial toxicology -- Periodicals; Environmentally induced diseases -- Periodicals; Toxicology -- Periodicals; 615.9005
• DOI: 10.1002/jat.3137
• Languages: English
• ISSNs: 0260-437X

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <p>DNA damage and cytotoxicity induced by a hydroxylated fullerene [C<sub>60</sub>(OH)<sub>24</sub>], which is a spherical nanomaterial and/or a water‐soluble fullerene derivative, and their protection by sulfhydryl compounds were studied in freshly isolated rat hepatocytes. The exposure of hepatocytes to C<sub>60</sub>(OH)<sub>24</sub> at a concentration of 50 μM caused time (0 to 3 h)‐dependent cell death accompanied by the formation of cell surface blebs, the loss of cellular levels of ATP and reduced glutathione, accumulation of glutathione disulfide, and induction of DNA fragmentation assayed using alkali single‐cell agarose‐gel electrophoresis. C<sub>60</sub>(OH)<sub>24</sub>‐induced cytotoxicity was effectively prevented by pretreatment with sulfhydryl compounds. <italic>N</italic>‐acetyl‐L‐cysteine (NAC), L‐cysteine and L‐methionine, at a concentration of 2.5 mM, ameliorated cell death, accompanied by a decrease in cellular ATP levels, formation of cell surface blebs, induction of reactive oxygen species (ROS) and loss of mitochondrial membrane potential caused by C<sub>60</sub>(OH)<sub>24</sub>. In addition, DNA fragmentation caused by C<sub>60</sub>(OH)<sub>24</sub> was also inhibited by NAC, whereas an antioxidant ascorbic acid did not affect C<sub>60</sub>(OH)<sub>24</sub>‐induced cell death and DNA damage in rat hepatocytes. Taken collectively, these results indicate that incubation of rat hepatocytes with C<sub>60</sub>(OH)<sub>24</sub> elicits DNA damage, suggesting that nuclei as well as mitochondria are target sites of the hydroxylated fullerene; and induction of DNA damage and oxidative stress is ameliorated by an increase in cellular GSH levels, suggesting that the onset of toxic effects may be partially attributable to a thiol redox‐state imbalance caused by C<sub>60</sub>(OH)<sub>24</sub>. Copyright © 2015 John Wiley & Sons, Ltd.</p> </abstract>