Lead exposure induced developmental nephrotoxicity in Japanese quail (Coturnix japonica) via oxidative stress-based PI3K/AKT pathway inhibition and NF-& kappa;B pathway activation

Birds are sensitive to environmental pollution and lead (Pb) contamination could negatively affect nearly all avian organs and systems including kidney of excretive system. Thereby, we used a biological model speciesJapanese quail (Coturnix japonica) to examine the nephrotoxic effects of Pb exposure and possible toxic mechanism of Pb on birds. Quail chicks of 7-day-old were exposed to 50 ppm Pb of low dose and high dose of 500 ppm and 1000 ppm Pb in drinking water for five weeks. The results showed that Pb exposure induced kidney weight increase while body weight and length reduction. The increase of uric acid (UA), creatinine (CREA) and cystatin c (Cys C) in the plasma suggested renal dysfunction. Moreover, both microstructural and ultrastructural changes demonstrated obvious kidney damages. In particular, renal tubule epithelial cells and glomeruli swelling indicated renal inflammation. Furthermore, changes in the content and activity of oxidative stress markers suggested that Pb caused excessive oxidative stress in the kidney. Pb exposure also induced abnormal apoptosis in the kidney. In addition, RNA sequencing (RNA-Seq) analysis revealed that Pb disturbed molecular pathways and signaling related with renal function. Especially, Pb exposure resulted in an increase in renal uric acid synthesis by disrupting purine metabolism. Pb caused apoptotic increment by inhibiting the phosphatidylinositol-3-kinase (PI3K)oC-alpha serine/threonine-protein kinase (AKT) pathway and induced aggravated inflammation by activating Nuclear Factor kappa B (NF-& kappa;B) signaling pathway. The study implied that Pb caused nephrotoxicity through structural damages, uric acid metabolism disorder, oxidation imbalance, apoptosis and inflammatory pathway activation.

Automated summary

Birds, especially Japanese quails, exposed to lead (Pb) contamination in drinking water showed an increase in kidney weight and a decrease in body weight and length. Pb exposure induced renal dysfunction, including abnormal uric acid metabolism, oxidative stress, apoptotic increment, and aggravated inflammation. The study revealed the nephrotoxic effects of Pb on birds through structural damages, disruption of purine metabolism, oxidation imbalance, apoptosis, and activation of the inflammatory pathway.