Pyraclostrobin Exposure Triggers Renal Injury by Activating Wnt/β-Catenin Signaling Pathway-Mediated Renal Fibrosis in Mice.

Authors

Yuanyuan Li, Bin Liu, Jingjing Chen, Binwu Zhuang, Dong Su, Yunlong Sang, Zibo Dong, Hao Liu

Published in

Journal of applied toxicology : JAT. Jun 28, 2026. Epub Jun 28, 2026.

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.

PMID:
42366128
Bibliographic data and abstract were imported from PubMed on 29 Jun 2026.

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