ArticleBiochimica et biophysica acta. Molecular and cell biology of lipids2019
A dual role of 12/15-lipoxygenase in LPS-induced acute renal inflammation and injury.
Article in Biochimica et biophysica acta. Molecular and cell biology of lipids, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 27 citations in OpenAlex.
- Experimental Characterization Combined with Computational Network Analysis of Metabolites Associated with Chrysanthemum morifolium-derived exosome-like Nanoparticles in Predicting Potential AKI-relevant Targets.Cell biochemistry and biophysics · 2026Article
- Natural compounds targeting inflammatory signaling and cell adhesion molecules in ischemic acute kidney injury.Archives of pharmacal research · 2026Review
- Targeting Inflammatory Imbalance in Chronic Kidney Disease: Focus on Anti-Inflammatory and Resolution Mediators.International journal of molecular sciences · 2025Review
- Exploring the role and therapeutic potential of lipid metabolism in acute kidney injury.Renal failure · 2024Review
- Anadenanthera colubrina regulated LPS-induced inflammation by suppressing NF-κB and p38-MAPK signaling pathways.Scientific reports · 2024Article
- 12-HETE activates Müller glial cells: The potential role of GPR31 and miR-29.Prostaglandins & other lipid mediators · 2024Article
- Deciphering ferroptosis in critical care: mechanisms, consequences, and therapeutic opportunities.Frontiers in immunology · 2024Review
- Sustained activation of 12/15 lipoxygenase (12/15 LOX) contributes to impaired renal recovery post ischemic injury in male SHR compared to females.Molecular medicine (Cambridge, Mass.) · 2023Article
- Article
- Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney.Nature reviews. Nephrology · 2023Review
- Tissue transglutaminase exacerbates renal fibrosis via alternative activation of monocyte-derived macrophages.Cell death & disease · 2023Article
- Hyperhomocysteinemia dysregulates plasma levels of polyunsaturated fatty acids-derived eicosanoids.Life research · 2022Article
- 15-Lipoxygenase worsens renal fibrosis, inflammation, and metabolism in a murine model of ureteral obstruction.American journal of physiology. Renal physiology · 2022Article
- Dual Effect of Soloxolone Methyl on LPS-Induced Inflammation In Vitro and In Vivo.International journal of molecular sciences · 2020Article
- Effect of berberine on LPS-induced expression of NF-Innate immunity · 2020Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
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Abstract
Recent studies suggest a potential role of bioactive lipids in acute kidney injury induced by lipopolysaccharide (LPS). The current study was designed to determine the profiling activities of various polyunsaturated fatty acid (PUFA) metabolizing enzymes, including lipoxygenases (LO), cyclooxygenase, and cytochrome P450 in the plasma of LPS-injected mice using LC-MS. Heat map analysis revealed that out of 126 bioactive lipids screened, only the 12/15-LO metabolite, 12-HETE, had a significant (2.24 ± 0.4) fold increase relative to control (P = 0.0001) after Bonferroni Correction (BCF α = 0.003). We then determined the role of the 12/15-LO in LPS-induced acute kidney injury using genetic and pharmacological approaches. Treatment of LPS injected mice with the 12/15-LO inhibitor, baicalein, significantly reduced levels of renal injury and inflammation markers including urinary thiobarbituric acid reactive substance (TBARs), urinary monocyte chemoattractant protein-1 (MCP-1), renal interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Similarly, knocking-out of 12/15-LO reduced levels of renal inflammation and injury markers elicited by LPS injection. Next, we tested whether exogenous supplementation with docosahexaenoic acid (DHA) as a substrate would divert the role of 12/15-LO from being pro-inflammatory to anti-inflammatory via increased production of the anti-inflammatory metabolite. DHA treatment restored the decreased in plasma level of resolvin D2 (RvD2) and reduced renal injury in LPS-injected mice whereas DHA treatment failed to provide any synergistic effects in reducing renal injury in LPS injected 12/15-LO knock-out mice. The ability of RvD2 to protect kidney against LPS-induced renal injury was further confirmed by exogenous RvD2 which significantly reduced the elevation in renal injury in LPS injected mice. These data suggest a double-edged sword role of 12/15-LO in LPS-induced acute renal inflammation and injury, depending on the type of substrate available for its activity.
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