Hepatocellular and developmental influences of early postnatal indomethacin in mice.

Abstract

The effect of early postnatal indomethacin exposure on hepatocellular and developmental alterations in mice liver was investigated. Pups received IP injections of 0, 25, 50 and 100 mg/kg indomethacin on P0, then killed at P21 and P60. Indomethacin significantly suppressed body weight at P21, but liver weight significantly decreased only in 25 mg/kg. In contrast, liver weight and liver to body weight ratio significantly increased with increasing dose of indomethacin by P60. The restoration of liver weight was a result of proliferation, as a consequence of a significant increase in the number of uni and bi-nuclear hepatocytes per field in 25 mg/kg at P21 and no evidence of hepatocellular hypertrophy. Indomethacin had a dose-related decrease in number of hepatocytes as the result of hepatocellular hypertrophy confirmed with hepatocytes presenting large cellular and nuclear size in 50 and 100 mg/kg. Moreover, proliferation contributed to the increased liver size, since bi-nuclear hepatocytes and its ratio increased at P21 at first and then decreased by P60 with increasing in dose. Indomethacin has long term effect on liver development in a dose- and time- dependent manner. The hepatocytes during both the liver development and regeneration show significant differences in cell and nuclear number and size (Tab. 3, Fig. 2, Ref. 48).