Hepatocellular and developmental influences of early postnatal indomethacin in mice.

OBJECTIVES: The effect of early postnatal indomethacin exposure on hepatocellular and developmental alterations in mice liver was investigated.

METHODS: Pups received IP injections of 0, 25, 50 and 100 mg/kg indomethacin on P0, then killed at P21 and P60.

RESULTS: 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.

CONCLUSION: 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).