ArticleLiver research (Beijing, China)2020
Pre-treatment twice with liposomal clodronate protects against acetaminophen hepatotoxicity through a pre-conditioning effect.
Article in Liver research (Beijing, China), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 6 citations in OpenAlex.
- The choroidal macrophage polarization significantly influences myopia development in murine models.iScience · 2026Article
- Mechanistic insights into hepatic cell type-specific contributions to acetaminophen-induced acute liver injury.World journal of gastroenterology · 2025Review
- GPR35 prevents drug-induced liver injury via the Gαs-cAMP-PKA axis in macrophages.Cellular and molecular life sciences : CMLS · 2025Article
- Article
- Enhancement of the Bioavailability and Anti-Inflammatory Activity of Glycyrrhetinic Acid via Novel SoluplusPharmaceutics · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
BACKGROUND AND
aimAcetaminophen (APAP) overdose is a major cause of acute liver injury, but the role of macrophages in propagation of the hepatotoxicity is controversial. Early research revealed that macrophage inhibitors protect against APAP injury. However, later work demonstrated that macrophage ablation by acute pre-treatment with liposomal clodronate (LC) exacerbates the toxicity. To our surprise, during other studies, we observed that pre-treatment
methodsWe treated mice with empty liposomes (LE) or LC twice per week for 1 week before APAP overdose and collected blood and liver tissue at 0, 2, and 6 h post-APAP. We then measured liver injury (serum ALT activity, histology), APAP bioactivation (total glutathione, APAP-protein adducts), oxidative stress (oxidized glutathione [GSSG]), glutamate cysteine-ligase subunit c (
resultsPre-treatment
conclusionsWe conclude that multiple pre-treatments with LC protect against APAP by accelerating glutathione re-synthesis through glutamate-cysteine ligase. Investigators using two or possibly more LC pre-treatments to deplete macrophages, including peritoneal macrophages, should be aware of this possible confounder.
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