1-O-hexyl-2, 3, 5-trimethylhydroquinone (HTHQ), a synthesized vitamin E derivative, is a superoxide scavenger which retains the original property of vitamin E as a natural lipophilic chain-breaking antioxidant. The present study was undertaken to evaluate the effects of HTHQ on hepatocyte apoptosis, using the carbon tetrachloride (CCl4)-induced rat hepatic cirrhosis model. We also clarified the changes in expression of naofen, previously reported as an intracellular WD-repeat protein associated with apoptosis. CCl4 was injected twice a week and HTHQ was mixed in the drinking water, with daily intake being allowed. Rats were divided into four groups: a CCl4-treated group, a CCl4 with daily intake of HTHQ group and solvent- or HTHQ-treated groups without CCl4. Within eight weeks in situ hybridization studies showed that naofen-positive hepatocytes elicited positive reactions in the TUNEL assay. CCl4 induced TUNEL-positive staining and also enhanced naofen mRNA expression in the livers. HTHQ inhibited both TUNEL staining and naofen expression caused by CCl4. Furthermore, the levels of naofen mRNA expression in CCl4-treated rat liver tissue were significantly reduced by treatment with HTHQ (1.90±0.18 vs. 1.29±0.08, p<0.01). HTHQ may inhibit both apoptosis and naofen expression in CCl4-treated rats, thus reducing liver cirrhosis.
Koji Tsunekawa, Jun An, Lei Huang, Toshiaki Nonami, Tatsuro Koide, Fumio Kondo, Hiroshi Nishikawa, Tokutaro Miki, Satoru Sugiyama and Naohisa Ishikawa, 2012. Effects of 1-O-hexyl-2, 3, 5-trimethylhydroquinone in Carbon Tetrachloride-induced Hepatic Apoptosis with a Possible Relationship to Naofen. International Journal of Pharmacology, 8: 434-439.