Protective Effects of Astilbin Against Cadmium-Induced Apoptosis in Chicken Kidneys via Endoplasmic Reticulum Stress Signaling Pathway

Abstract

Cadmium (Cd) can cause endoplasmic reticulum stress (ERS) and apoptosis in animals. The kidney is an organ seriously affected by Cd because it can accumulate metal ions. Astilbin (ASB) is a dihydroflavonol rhamnoside, which has an anti-renal injury effect. This study aimed to evaluate the protective effect of ASB on Cd-induced ERS and apoptosis in the chicken kidney. In this study, a total of 120 1-day-old chickens were randomly divided into 4 groups. Chickens were fed with a basic diet (Con group), ASB 40 mg/kg (ASB group), CdCl₂ 150 mg/kg + ASB 40 mg/kg (ASB/Cd group), and CdCl₂ 150 mg/kg (Cd group) for 90 days. The results showed that Cd exposure induced pathological and ultrastructural damages and apoptosis in chicken kidneys. Compared with the Con group, metallothionein (MT1/MT2) level, nitric oxide (NO) content, inducible nitric oxide synthase (iNOS) activity, ERS-related genes 78-kDa glucose-regulated protein (Grp78), protein kinase PKR-like endoplasmic reticulum kinase (Perk), activating transcription factor 4 (Atf4) and CAAT/enhancer-binding protein (C/EBP) homologous protein (Chop), and pro-apoptotic gene B-cell lymphoma 2 (Bcl-2)-associated X (Bax), caspase-12, caspase-9, caspase-3 expression levels, and apoptotic rate were significantly increased in the Cd group. The expression level of Bcl-2 was significantly decreased in the Cd group. ASB/Cd combined treatment significantly improves the damage of chicken kidneys by ameliorating Cd-induced kidney ERS and apoptosis. Cd can cause the disorder of the GRP78 signal axis, activate the PERK-ATF4-CHOP pathway, aggravate the structural damage and dysfunction of ER, and promote the apoptosis of chicken kidneys, while the above changes were significantly alleviated in the ASB/Cd group. The results showed that ASB antagonizes the negative effects of Cd and against Cd-induced apoptosis in chicken kidneys via ERS signaling pathway.

Keywords: Apoptosis; Astilbin,; Cadmium,; Endoplasmic reticulum stress,; PERK,.