Alcohol may induce hepatic necrosis, and the subsequent inflammatory cell infiltration in the liver may form foci of necroinflammation (17). After 4 weeks of ethanol feeding, necrotic foci with clusters of inflammatory cells were observed to a greater extent in liver sections from cyp2a5−/− mice than from cyp2a5+/+ mice (Fig 2A right panels and B black bars). Although the serum levels of total bilirubin and serum activity of ALP were not changed after ethanol feeding in either cyp2a5−/− or cyp2a5+/+ mice (data not shown), the serum levels of ALT and AST, markers of liver injury, were elevated in cyp2a5−/− mice to a greater extent than in cyp2a5+/+ mice (Fig 2C). The ratio of liver to body weight was increased by ethanol feeding, but there was no difference between cyp2a5−/− mice and cyp2a5+/+ mice (Fig 2D). Collagen I and α-SMA were detected by IHC. Although expression of collagen I was induced by ethanol feeding, collagen was mainly located in the sinusoid space and no evident fibrosis was observed (Fig. 2E middle panels). Also, we did not observe positive staining for α-SMA in the liver sections except for blood vessel walls (Fig. 2E right panels).
