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Cytotoxic Effects of Thioxanthone Derivatives as Photoinitiators on Isolated Rat Hepatocytes

Cytotoxic Effects of Thioxanthone Derivatives as Photoinitiators on Isolated Rat Hepatocytes

Yoshio Nakagawa, Akiko Inomata, Takako Moriyasu, Toshinari Suzuki

J Appl Toxicol. 2020 Feb;40(2):234-244.

PMID: 31633820

Abstract:

Thioxanthone and its analogues, 2- or 4-isopropylthioxanthone, 2-chlorothioxanthone, 2,4-diethylthioxanthone (DETX) and xanthone, are used as photoinitiators of ultraviolet (UV) light-initiated curable inks. As these photoinitiators were found in numerous food/beverage products packaged in cartons printed with UV-cured inks, the cytotoxic effects and mechanisms of these compounds were studied in freshly isolated rat hepatocytes. The toxicity of DETX was greater than that of other compounds. DETX elicited not only concentration (0-2.0 mm)- and time (0-3 hours)-dependent cell death accompanied by the depletion of cellular adenosine triphosphate (ATP), and reduced glutathione (GSH) and protein thiol levels, but also the accumulation of GSH disulfide and malondialdehyde. Pretreatment of hepatocytes with either fructose at a concentration of 10 mm or N-acetyl-l-cysteine (NAC) at a concentration of 5.0 mm ameliorated DETX (1 mm)-induced cytotoxicity. Further, the exposure of hepatocytes to DETX resulted in the induction of reactive oxygen species (ROS) and loss of mitochondrial membrane potential, both of which were partially prevented by the addition of NAC. These results indicate that: (1) DETX-induced cytotoxicity is linked to mitochondrial failure and depletion of cellular GSH; (2) insufficient cellular ATP levels derived from mitochondrial dysfunction were, at least in part, ameliorated by the addition of fructose; and (3) GSH loss and/or ROS formation was prevented by NAC. Taken collectively, these results suggest that the onset of toxic effects caused by DETX may be partially attributable to cellular energy stress as well as oxidative stress.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP83846860	4-Isopropylthioxanthone		83846-86-0	Price

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