Effects of sulcotrione [2-(2-chloro-4-mesylbenzoyl)-cyclohexane-1,3-dione] on enzymes involved in tyrosine catabolism and the extent of the resulting tyrosinemia and its relationship with corneal lesions in rats

We aimed to investigate the effects of subchronic exposure to sulcotrione on the enzymes involved in tyrosine catabolism and the extent of the resulting tyrosinemia and corneal lesions in rats. Daily oral administration of sulcotrione at 0.1, 0.5, 5, 50 and 100 mg/kg/day markedly inhibited hepatic 4-hydroxyphenylpyruvate dioxygenase (HPPD). In response to the tyrosinemia, the activity of hepatic tyrosine aminotransferase (TAT) at each dose level was insignificantly induced and hepatic homogentisic acid oxidase (HGO) at 5, 50 and 100 mg/kg/day was markedly reduced. Repeated oral administration of sulcotrione to rats at doses of 5, 50, and 100 mg/kg/day for 90 days produced corneal lesions with an incidence of 18.8%, 75.0% and 56.3%, respectively. The significant increase in tyrosine levels indicates that the occurrence of corneal lesions in rats exposed to sulcotrione was not only associated with the concentration of tyrosine in the ocular fluid, but also with other, unidentified factors.

Graphical abstractThe rats were administered with sulcotrione and the effects were observed on the enzymes involved in tyrosine catabolism and the extent of the resulting tyrosinemia and corneal lesions.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► We study the effects exposure to sulcotrione in rats. ► Sulcotrione markedly inhibited hepatic 4-hydroxyphenylpyruvate dioxygenase (HPPD). ► Oral administration of sulcotrione to rats for 90 days produced corneal lesions. ► The corneal lesions in rats were associated with the unidentified factors.