FIG. 7.

Lack of MnSOD in hepatocytes causes liver damage. (A) Livers from 3-month-old, male MnSOD^flox/flox control mice (WT) and MnSOD-KO mice (KO) were prepared and analyzed for morphological changes. Cells showing mitotic signs, inflammatory infiltrates, and lipid droplets were counted using a ×400 magnification (0.15 mm² field), and the respective index (nuclei with visible chromosomes/total number of nuclei with observations at least 5000 counted nuclei) as well as the Knodell fibrosis score (33) compared to the WT animals, was determined. Data presented as mean ± SD (n = 6/group; *p < 0.05). (B) Representative liver sections from wild-type MnSOD^flox/flox (WT) and hepatocyte-specific MnSOD-KO mice stained with hematoxylin/eosin. The livers of hepatocyte-specific MnSOD-KO mice displayed sings of inflammation (inflammatory foci in the middle panel in KO). In addition, an enhanced number of mitotic cells (arrow in left KO) and lipid droplet containing cells (right KO) were present in these animals. (C) Blood was drawn from 3-month-old, male control MnSOD^flox/flox mice (WT) and MnSOD-KO mice (KO); the individual samples of serum were analyzed for different parameters indicating liver injury. The respective levels or activities in the WT animals were set to 1 (*Significant difference p < 0.05). (D) Serum parameters in the WT and KO mice, values represent mean ± SD (n = 6/group; *p < 0.05,). Alb, albumin; ALP, alkaline phosphatase; ALT, alanine aminotransferase (formerly GPT, glutamate pyruvate aminotransferase); AST, aspartate aminotransferase (formerly GOT, glutamate oxaloacetate aminotransferase); Bili, bilirubin; Che, choline esterase. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars