Effects of 1-O-hexyl-2,3,5-trimethylhydroquinone on carbon tetrachloride-induced hepatic cirrhosis in rats.
OBJECTIVE
The present study was undertaken to evaluate the effects of 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), a synthesized vitamin E derivative, on carbon tetrachloride (CCl(4))-induced cirrhosis.


METHODS
Rats were treated with hypodermic injections of CCl(4) twice a week to induce the hepatic cirrhosis, and given drinking water containing HTHQ or solvent. Primary cultures of rat hepatocytes were performed to evaluate the effects of HTHQ on the expression of inducible nitric oxide synthase (iNOS).


RESULTS
Masson's staining of rat livers showed fibrosis around pseudo-lobules in the CCl(4) group, the lesions being reduced in the CCl(4) HTHQ group. Increases in liver tissue hydroxyproline and alpha(1)(I) collagen, alpha-smooth muscle actin and iNOS induced by CCl(4), were also markedly diminished by HTHQ. Furthermore, both HTHQ and vitamin E attenuated interleukin-1beta-induced iNOS protein expression in cultured hepatocytes, the potency of HTHQ being 10-times higher than that of vitamin E.


CONCLUSIONS
HTHQ may inhibit development of hepatic cirrhosis in rats, more potently than vitamin E, by inhibiting the iNOS expression in hepatocytes. Because vitamin E has a radical scavenging action, roles of NO and peroxynitrite will be discussed in the effects of HTHQ on the fibrosis.
An
Jun
J
Department of Pharmacology, Aichi Medical University School of Medicine, Nagakute, Japan.
Feng
Guo-Gang
GG
Huang
Lei
L
Kurokawa
Tsuyoshi
T
Nonami
Toshiaki
T
Koide
Tatsuro
T
Kondo
Fumio
F
Komatsu
Toru
T
Tsunekawa
Koji
K
Fujiwara
Yoshihiro
Y
Goto
Hidemi
H
Nishikawa
Hiroshi
H
Miki
Tokutaro
T
Sugiyama
Satoru
S
Ishikawa
Naohisa
N