In rat models of cholestasis, when cholestasis is moderate, mRNA and protein expression of CYP3A1 is significantly increased while the expression of CYP3A2 is unchanged; the expression and activity of both enzymes are sharply lower in severe cholestasis; CYP3A1 and CYP3A2 are the metabolically most important isoforms of CYP3A in male rats [280]. This evidence concerns the gene CYP3A4 and cholestasis.