Idoxifene is a tissue-specific selective estrogen receptor modulator.

Idoxifene functions as an estrogen agonist in osteoblasts within the bone, while exhibiting minimal agonist activity in human endometrial cells. It, alongside E2, shields hepatocytes from damage caused by inflammatory cells through the inhibition of NF-κB, a proinflammatory transcription factor [2]. Additionally, Idoxifene safeguards vascular smooth muscle cells by mitigating the production of reactive oxygen species triggered by angiotensin II. It also notably reduces hepatic stellate cell (HSC) activation, curtails the proliferation of culture-activated HSCs in a dose-dependent manner, and promotes the apoptosis of these cells over time [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].