Nevertheless, detrimental effects associated with chronic HO-1 upregulation could also be present in RIP3−/− mice following BDL;25, 33, 34 RIP3 deficiency exacerbated cholestasis and jaundice 14 days after BDL, as evidenced by increased levels of bilirubin and AP, likely due to sustained overexpression of HO-1. Here, HMOX1 is linked to cholestasis.