Lead exposure induced developmental nephrotoxicity in Japanese quail (Coturnix japonica) via oxidative stress-based PI3K/AKT pathway inhibition and NF-κB pathway activation.
Comp Biochem Physiol C Toxicol Pharmacol
; 268: 109599, 2023 Jun.
Article
em En
| MEDLINE
| ID: mdl-36893933
ABSTRACT
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 species-Japanese 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)/RAC-alpha serine/threonine-protein kinase (AKT) pathway and induced aggravated inflammation by activating Nuclear Factor kappa B (NF-κB) signaling pathway. The study implied that Pb caused nephrotoxicity through structural damages, uric acid metabolism disorder, oxidation imbalance, apoptosis and inflammatory pathway activation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
2_ODS3
Problema de saúde:
2_quimicos_contaminacion
Assunto principal:
NF-kappa B
/
Coturnix
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Comp Biochem Physiol C Toxicol Pharmacol
Assunto da revista:
FARMACOLOGIA
/
TOXICOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China