Hepatocellular and developmental influences of early postnatal indomethacin in mice

Area of Science:

• Hepatology
• Developmental Biology
• Pharmacology

Background:

• Non-steroidal anti-inflammatory drugs (NSAIDs) like indomethacin are commonly used.
• Understanding the long-term effects of early-life drug exposure is crucial for developmental health.
• The impact of indomethacin on liver development requires further investigation.

Purpose of the Study:

• To investigate the effects of early postnatal indomethacin exposure on mouse liver development.
• To determine dose- and time-dependent alterations in hepatocellular structure and liver growth.

Main Methods:

• Mouse pups were exposed to varying doses of indomethacin (0, 25, 50, 100 mg/kg) via intraperitoneal injection on postnatal day 0 (P0).
• Liver tissues were analyzed at postnatal days 21 (P21) and 60 (P60).
• Evaluations included body weight, liver weight, liver-to-body weight ratio, and hepatocyte morphology (size, nuclear characteristics, and number).

Main Results:

• Indomethacin suppressed body weight at P21, with liver weight decreasing only at 25 mg/kg.
• By P60, liver weight and liver-to-body weight ratio increased with higher indomethacin doses.
• Hepatocellular proliferation, indicated by increased uni- and bi-nuclear hepatocytes, contributed to liver restoration, while higher doses (50 and 100 mg/kg) led to hepatocellular hypertrophy and decreased hepatocyte numbers.

Conclusions:

• Indomethacin exerts long-term effects on liver development in a dose- and time-dependent manner.
• Significant alterations in hepatocyte cell and nuclear size and number were observed during liver development and regeneration.
• These findings highlight the potential for NSAID-induced developmental toxicity in the liver.