Extrahepatic lesions induced by acetaminophen in the mouse
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Published on: May 31, 2018
M E Placke1, D S Wyand, S D Cohen
1Department of Pathobiology, School of Pharmacy, University of Connecticut, Storrs 06268.
Abstract:
Acetaminophen in acute overdose is primarily recognized as potentially hepatotoxic with few descriptions of extrahepatic lesions other than nephrotoxicity. Fasted adult, male mice, both standard and germ-free, were given acetaminophen orally and killed at selected times, from 30 minutes to 48 hours after treatment. In addition to the expected hepatic effects after 600 mg acetaminophen/kg, degenerative and necrotic changes were found in four non-hepatic tissues. Nephrosis developed 2 to 4 hours after treatment and paralleled the course of hepatic damage. Necrosis of bronchiolar epithelium in the absence of inflammation was evident 4 to 6 hours after acetaminophen administration as was onset of testicular changes. Spermatidic degeneration with early development of spermatidic multinucleated giant cells were characteristic features. Areas of lymphoid necrosis were also visible in splenic follicles and Peyer's patches 18 to 24 hours after treatment. These observations have demonstrated that other tissues in addition to liver and kidney are damaged by acetaminophen toxicity and should be considered in cases of acetaminophen overdosage.
Insights
Acetaminophen overdose causes more than liver and kidney damage. Studies show toxicity affects lungs, testes, spleen, and Peyer's patches, highlighting broader health risks.
Area of Science:
- Toxicology
- Pharmacology
- Pathology
Background:
- Acetaminophen (APAP) overdose is a leading cause of acute liver failure.
- Extrahepatic manifestations, primarily nephrotoxicity, are less documented.
- Limited understanding of APAP's systemic toxic effects beyond the liver and kidneys.
Purpose of the Study:
- To investigate the extrahepatic toxic effects of acetaminophen in an acute overdose model.
- To identify specific non-hepatic tissues affected by acetaminophen toxicity.
- To characterize the temporal development of these extrahepatic lesions.
Main Methods:
- Administration of acetaminophen (600 mg/kg) to fasted adult male mice (standard and germ-free).
- Oral administration route for acetaminophen.
- Necropsy and histological examination at various time points (30 minutes to 48 hours).
Main Results:
- Acetaminophen induced nephrosis, paralleling hepatic damage (2-4 hours).
- Necrosis of bronchiolar epithelium (4-6 hours) and testicular damage (spermatidic degeneration, multinucleated giant cells) were observed.
- Lymphoid necrosis in splenic follicles and Peyer's patches noted (18-24 hours).
Conclusions:
- Acetaminophen toxicity extends beyond the liver and kidneys.
- Four additional non-hepatic tissues (lungs, testes, spleen, Peyer's patches) are susceptible to acetaminophen-induced damage.
- These findings necessitate consideration of broader organ involvement in acetaminophen overdosage cases.
