Hepatocellular proliferation in ibuprofen-treated mice

Area of Science:

• Toxicology
• Hepatology
• Pharmacology

Background:

• Ibuprofen is a widely used nonsteroidal anti-inflammatory drug (NSAID).
• Understanding its effects on liver health, particularly hepatocellular changes, is crucial.

Purpose of the Study:

• To investigate the effects of acute and subchronic ibuprofen exposure on hepatocellular proliferation and liver weight in female B6C3F1 mice.
• To determine the contribution of hepatocellular hypertrophy and hyperplasia to ibuprofen-induced hepatomegaly.

Main Methods:

• Mice were treated with varying doses of ibuprofen for 2 weeks or 90 days.
• Hepatocellular proliferation was assessed using bromodeoxyuridine labeling.
• Liver weights, hepatocyte density, and ultrastructural changes (peroxisome size) were evaluated.

Main Results:

• Short-term (2-week) ibuprofen treatment led to dose-dependent increases in liver weight, hepatocellular proliferation, and hypertrophy.
• Ultrastructural analysis revealed enlarged hepatocyte peroxisomes in ibuprofen-treated mice.
• Long-term (90-day) treatment resulted in increased relative liver weights but without significant increases in hepatocellular proliferation or hypertrophy.
• Decreased serum triglycerides were observed with longer-term ibuprofen exposure.

Conclusions:

• Ibuprofen induces hepatomegaly in mice, involving both hepatocellular hypertrophy and hyperplasia, especially during acute exposure.
• Peroxisomal alterations may play a role in the development of ibuprofen-induced liver lesions.
• The effects on liver morphology differ between acute and subchronic exposure durations.