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Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen
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Generation of a Rat Model of Acute Liver Failure by Combining 70% Partial Hepatectomy and Acetaminophen

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Mannan-binding lectin attenuates acetaminophen-induced hepatotoxicity by regulating CYP2E1 expression via

Huifang Li1,2,3, Yan Liu1,2, Junru Li1,4

  • 1Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

European Journal of Immunology
|February 2, 2019
PubMed

Insights

Mannan-binding lectin (MBL) deficiency worsens acetaminophen-induced liver injury by increasing toxic metabolism and oxidative stress. MBL protects against drug-induced liver damage through a mechanism involving reactive oxygen species and CYP2E1.

Area of Science:

  • Immunology
  • Hepatology
  • Pharmacology

Background:

  • Mannan-binding lectin (MBL) is a key innate immune system pattern recognition molecule.
  • MBL deficiency is common and linked to liver disease susceptibility.
  • Acetaminophen (APAP) overdose causes significant drug-induced liver injury.

Purpose of the Study:

  • To investigate the role of MBL in APAP-induced hepatotoxicity.
  • To elucidate the underlying mechanisms of MBL's protective effects against liver injury.

Main Methods:

  • Utilized MBL-deficient (MBL-/-) mice and human HepaRG cells.
  • Administered APAP to induce hepatotoxicity.
  • Measured mortality, liver enzymes, APAP metabolism, reactive oxygen species (ROS), JNK activation, SP1 expression, and CYP2E1 levels.

Main Results:

  • MBL-/- mice exhibited higher mortality, aggravated liver necrosis, and elevated liver enzymes post-APAP treatment.
  • Hepatotoxicity in MBL-/- mice correlated with increased APAP toxic metabolites.
  • MBL deficiency led to excessive ROS production, enhanced JNK activation, and increased SP1/CYP2E1 expression, exacerbating liver injury.
  • MBL demonstrated protective effects against APAP toxicity in vitro.

Conclusions:

  • MBL plays a crucial protective role in mitigating acetaminophen-induced liver injury.
  • MBL deficiency exacerbates APAP hepatotoxicity via increased oxidative stress and altered drug metabolism.
  • This study reveals a novel function of MBL in drug metabolism and provides insights into drug-induced liver injury in MBL-deficient individuals.
Keywords:
CYP2E1JNK/SP1acetaminophenmannan-binding lectinreactive oxygen species

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