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Pyraclostrobin Exposure Triggers Renal Injury by Activating Wnt/β-Catenin Signaling Pathway-Mediated Renal Fibrosis
Yuanyuan Li1,2, Bin Liu1, Jingjing Chen2
1Department of Thoracic Surgery, The Affiliated Hospital of Kangda College of Nanjing Medical University (The Ganyu District People's Hospital of Lianyungang City), Lianyungang, China.
Abstract:
Pyraclostrobin (PY) is a commonly applied strobilurin-class fungicide that is frequently identified as a residue in food products, yet its nephrotoxic mechanisms remain unclear. Here, a 28-day oral gavage mouse model (1/10 and 1/5 LD50) and an HK-2 cell model (1/10 and 1/5 IC50) were established to investigate PY-induced nephrotoxicity. Histopathological analysis revealed glomerular hypertrophy, mesangial expansion, inflammatory infiltration, capillary congestion, and tubular epithelial degeneration. Biochemical assays revealed that PY significantly elevated the levels of blood urea nitrogen (BUN), creatinine (CRE), kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL), indicating impaired renal function. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis further demonstrated increased mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), accompanied by decreased interleukin-10 (IL-10) expression. Masson's staining and protein analyses confirmed enhanced extracellular matrix deposition and fibrosis, with increased expression of collagen I, transforming growth factor-β1 (TGF-β1), α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF). Moreover, PY markedly activated the Wnt/β-catenin signaling pathway, as evidenced by elevated levels of phosphorylated β-catenin (P-β-catenin), β-catenin, c-Myc, phosphorylated glycogen synthase kinase-3β (P-GSK3β), and Cyclin D1. Inhibition with ICG-001 significantly attenuated PY-induced fibrosis, confirming Wnt/β-catenin-dependent effects. These findings provide mechanistic insight into PY-induced renal injury and fibrosis.
Insights
Pyraclostrobin (PY) fungicide causes kidney damage and fibrosis by activating the Wnt/β-catenin pathway. This study reveals the mechanisms behind PY-induced nephrotoxicity, offering insights into its health risks.
Area of Science:
- Environmental Toxicology
- Renal Pathology
- Molecular Mechanisms
Background:
- Pyraclostrobin (PY) is a widely used strobilurin fungicide with residues found in food.
- The specific mechanisms underlying PY-induced kidney toxicity (nephrotoxicity) are not well understood.
Purpose of the Study:
- To investigate the nephrotoxic effects and underlying mechanisms of Pyraclostrobin (PY) exposure.
- To elucidate the role of the Wnt/β-catenin signaling pathway in PY-induced renal fibrosis.
Main Methods:
- Established 28-day oral gavage mouse and HK-2 cell models for PY exposure.
- Performed histopathological analysis, biochemical assays (BUN, CRE, KIM-1, NGAL), qRT-PCR, and Western blotting.
- Utilized Masson's staining and Wnt/β-catenin pathway inhibitors (ICG-001) to assess fibrosis and pathway activation.
Main Results:
- PY exposure caused significant kidney damage, including glomerular hypertrophy, inflammation, and tubular degeneration.
- Elevated markers of renal dysfunction (BUN, CRE, KIM-1, NGAL) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β) were observed.
- PY induced renal fibrosis by promoting extracellular matrix deposition via activation of the Wnt/β-catenin signaling pathway.
Conclusions:
- Pyraclostrobin (PY) induces significant nephrotoxicity and renal fibrosis.
- The Wnt/β-catenin signaling pathway plays a critical role in mediating PY-induced renal fibrosis.
- Findings provide mechanistic insights into PY-associated kidney injury, highlighting potential health concerns.
