Idoxifene is a tissue-specific selective estrogen receptor modulator.

Idoxifene acts in the bone as an estrogen agonist for osteoblasts and shows negligible agonist activity in human endometrial cells. Idoxifene and E2 protect hepatocytes from inflammatory cell injury by inhibiting activation of the NF-κB proinflammatory transcription factor [2]. Idoxifene possesses the protective roles in vascular smooth muscle cells by blunting the angiotensin II-induced production of reactive oxygen species. Idoxifene evidently suppresses HSC activation, inhibits culture-activated HSC proliferation in a dose-dependent manner, and induces culture-activated HSC apoptosis in a time-dependent manner [1].

Idoxifene at doses of over 0.1 mg/kg significantly reduces the hepatic levels of collagen and MDA in the DMN model in a dose-dependent manner. Animals receive daily intraperitoneal injections of Estradiol (0.5 mg/kg) and an oral gavage of Idoxifene (0.02, 0.1, and 0.5 mg/kg) for 3 days after Dimethylnitrosamine (DMN) treatment. Although Idoxifene and E2 are administered by different routes, i.e., by oral ingestion and intraperitoneal injection, respectively. However, the antifibrotic effect of a dose of 0.5 mg/kg of Idoxifene is somewhat greater than that of the same dose of E2 [2].