Dimethylthiourea ameliorates carbon tetrachloride-induced acute liver injury in ovariectomized mice

Abstract

Aims: In order to clarify hepato-protective actions of estrogen, we examined the progress of carbon tetrachloride (CCl₄)-induced acute liver injury (ALI) in sham and ovariectomized (ovx) mice and the effects of dimethylthiourea (DMTU), a hydroxyl radical scavenger, and meloxicam (Melo), a selective cox-2 inhibitor, on the development of CCl₄-induced ALI.

Main methods: Female C57BL/6 J mice weighing 15-20 g were performed sham or ovx operation at 8 weeks of age. Blood and liver samples were collected 15 and 24 h after CCl₄ administration. Sham and ovx mice were given DMTU, Melo or saline intraperitoneally 30 min before CCl₄ or corn oil administration.

Key findings: ALT levels in ovx mice were significantly increased compared to those in sham mice. DMTU reduced ALT levels in ovx mice to the same levels as those in sham mice after CCl₄ injection. CCl₄ upregulated TNF-α, IL-6, cox-2 and iNOS expression in ovx mice compared to the levels in sham mice. DMTU significantly reduced cox-2 and iNOS expression levels upregulated by CCl₄ in ovx mice. However, pretreatment with Melo had no effects on ALT levels and the gene expression levels of TNF-α, IL-6 and HO-1 in either sham or ovx mice, indicating that cox-2 may not participate in increase of CCl₄-induced ALI caused by estrogen deficiency.

Significance: Ovariectomy accelerated the development of CCl₄-induced acute liver injury, and DMTU reduced liver injury. These results suggest that estrogen may act as an antioxidant in the development CCl₄-induced acute liver injury.

Keywords: Carbon tetrachloride-induced acute liver injury; Dimethylthiourea; Estrogen; Ovariectmized; Oxidative stress.