Drug-induced lenticular opacity and accumulation of cholesterol-related substances in the lens cortex of dogs.

Drug-induced lenticular opacity and accumulation of cholesterol-related substances in the lens cortex of dogs. J Toxicol Sci. 2020;45(4):201-218 Authors: Iwasaki H, Wakamatsu M, Sugihara K, Kamio K, Tsuji S, Morita J, Kurihara Y, Izumi T, Nishimoto T, Kinoshita K, Nakanishi Y, Sasaki M Abstract TP0446131, developed as an antidepressant agent, was found to cause lenticular opacity in a 13-week repeated-dose study in dogs. Histopathologically, the lenticular opacity was observed as a degeneration of the lens fibers, characterized by irregularity in the ordered arrangement of the fibers which is necessary to maintain the transparency of the lens, and was considered to manifest clinically as cataract. To evaluate the development mechanism of the lenticular opacity, the chemical constituents of the lens, which is known to be associated with the development of cataract, were examined. The results of liquid chromatography-tandem mass spectrometry analysis revealed an increase in the amplitudes of 3 unknown peaks in a dose- and time-dependent manner in the lens, with no remarkable changes in the other chemical components tested. In addition, the content of cholesterol, alterations of which have been reported to be associated with cataract, remained unchanged. The mass spectral data and chromatographic behavior of the 3 peaks indicated that these peaks corresponded to sterol-related substances, and that one of them was 7-dehydrocholesterol, a...
Source: Journal of Toxicological Sciences - Category: Toxicology Tags: J Toxicol Sci Source Type: research