Abstract: TH-PO0424
Evaluation of Nephrotoxic and Neurotoxic Effects of Quinolinic Acid in a Zebrafish Podocyte Injury Model
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Capasso, Giovambattista, Biology and Molecular Genetics Institute, Ariano Irpino, Avellino, Italy
- Miele, Antonio, Biology and Molecular Genetics Institute, Ariano Irpino, Avellino, Italy
- Romano, Mariacarmela, Biology and Molecular Genetics Institute, Ariano Irpino, Avellino, Italy
- D'Apolito, Luciano, Biology and Molecular Genetics Institute, Ariano Irpino, Avellino, Italy
- Iannaccone, Antonella, University "Luigi Vanvitelli", Napoli, Italy
- Iervolino, Anna, Biology and Molecular Genetics Institute, Ariano Irpino, Avellino, Italy
Background
Quinolinic acid (QA) is a metabolite of the kynurenine pathway known for its neurotoxicity in preclinical models and for accumulating in CKD patients. Zebrafish models offers a versatile system to assess renal and neurotoxicity. pod::NTR-mCherry transgenic zebrafish line expresses nitroreductase specifically in podocytes, allowing selective induction of apoptosis via metronidazole treatment. Our study on this model investigates whether QA exacerbates glomerular injury, and induces neurotoxic effects in zebrafish, providing insights into potential risks in patients with compromised renal function.
Methods
Cherry larvae at 4 days post-fertilization (dpf) were treated with MTZ. Survival, renal damage, edema were assessed, and glomerular filtration was quantified using FITC-dextran 500 kDa. QA was administered to wild-type larvae and larvae with glomerular injury. To study neuronal activity, zebrafish CaMPARI2 line were used. After treatment with QA, comparing the red/green fluorescence ratios between treated and untreated groups using intravital microscopy was possible to assess how the QA altered the activity of neural circuits. The neurotoxicity was evaluated using a Light–Dark transition test with DanioVision, recording locomotor activity. Real-time PCR on larvae was assessed to evaluate inflammatory and tubular injury markers.
Results
Larvae treated with QA in combination with MTZ exhibited accelerated glomerular injury compared to MTZ alone. Kim1 expression was significantly increased in the MTZ+QA group, suggesting additional tubular injury. In light–dark tests, QA, alone or combined with MTZ, significantly reduced locomotor speed in all phases, indicating pronounced hypoactivity. Using CaMPARI2 larvae, after QA injections, there was an increase neuronal hyperactivation, which manifested at the locomotor level with a reduction in locomotor performance. Moreover, real-time PCR revealed a significant increase in IL1b expression in QA and MTZ+QA groups, suggesting activation of inflammatory responses.
Conclusion
QA accelerates glomerular injury, induces inflammation, and potentially causes neurotoxicity in zebrafish larvae, independently of renal damage, leading to calcium overload, oxidative stress, and initial neuronal dysfunction. These results provide preclinical evidence of QA’s systemic toxic effects and underscore the importance of monitoring QA accumulation in CKD patients.