Male WT and Mdr2−/− mice (8 weeks of age) were implanted with osmotic minipumps to deliver 0.9% NaCl (saline) or 10 mg/kg BW/day (18 (link), 19 (link)) of either mepyramine (H1HR antagonist), ranitidine (H2HR antagonist). In separate experiments, male Mdr2−/− mice (8 weeks of age) were treated with a combination of mepyramine and ranitidine (H1HR/H2HR antagonist) for 4 weeks to mimic chronic usage. Male mice (8 – 10 mice per group) were euthanized at 12 weeks of age, where these mice display an increase in PSC-induced hepatic damage (7 , 10 (link)). From these groups, we collected liver blocks (frozen and paraffin-embedded), serum, cholangiocytes and cholangiocyte supernatants, as described (7 , 20 ).