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Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
Published on: November 27, 2019
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Intestinal injury in paracetamol overdose (ATOM-8)
Varan Perananthan1,2, Fathima Shihana1,2, Angela L Chiew2,3,4
1Edith Collins Centre, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Journal of Gastroenterology and Hepatology
|December 27, 2023
Summary
Paracetamol overdose causes intestinal toxicity, indicated by elevated intestinal fatty acid binding protein (IFABP). This toxicity may explain early hyperlactatemia and impacts drug absorption and liver damage.
Area of Science:
- Toxicology
- Gastroenterology
- Pharmacology
Background:
- Paracetamol (acetaminophen) overdose is known for liver damage.
- Intestinal toxicity from high paracetamol levels during absorption is less understood.
- This study investigates paracetamol-induced intestinal injury.
Purpose of the Study:
- To determine if paracetamol overdose causes intestinal toxicity.
- To correlate intestinal damage markers with early and late paracetamol toxicity.
- To explore the link between intestinal toxicity and hyperlactatemia.
Main Methods:
- Analyzed plasma intestinal fatty acid binding protein (IFABP) and gut microRNAs in 30 overdose patients.
- Measured markers of enterocyte damage.
- Performed sub-analysis on patients with early hyperlactatemia (lactate > 2 mmol/L within 12h).
Main Results:
- Plasma IFABP was significantly elevated in paracetamol overdose patients versus controls.
- Patients with early hyperlactatemia showed higher IFABP levels.
- IFABP correlated with paracetamol and lactate concentrations; miR-122 and miR-215 were downregulated in early hyperlactatemia.
Conclusions:
- Paracetamol overdose induces concentration-dependent intestinal toxicity.
- Intestinal toxicity may explain early hyperlactatemia syndrome.
- Intestinal toxicity could affect drug absorption and hepatotoxicity progression.
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