1,8-cineole alleviates bisphenol A-induced apoptosis and necroptosis in bursa of Fabricius in chicken through regulating oxidative stress and PI3K/AKT pathway.

Abstract

Bisphenol A (BPA), an important chemical raw material, is now a ubiquitous environmental contaminant. As an endocrine disruptor similar to estrogen, BPA increases the risk of various metabolic and chronic diseases. BPA has immunotoxicity to humans and animals. 1,8-cineole (CIN) is a plant-derived monoterpene with antioxidant and antiapoptosis actions. However, there are no reports about whether CIN could antagonize the BPA-induced apoptosis and necroptosis in bursa of Fabricius (BF) of chicken. This study was to elucidate the ameliorative mechanism of CIN on the apoptosis and necroptosis in BF induced by BPA. 120 broilers (1-day-old) were randomly divided into four groups: control group, CIN group, CIN and BPA co-treatment group, and BPA group. TUNEL analysis results, histopathological variations, and the overexpression of proapoptosis biomakers (Caspase 3, Bax, Cyt-c, and p53) and necroptosis pathway-related factors (RIPK1, RIPK3, MLKL, and FADD) indicated that BPA exposure induced the apoptosis and necroptosis in chicken BF. Moreover, BPA treatment elevated the levels of oxidative stress indexes (MDA, iNOS, and NO) and weaken antioxidases activity (SOD, GPx, and CAT) and total antioxidant capacity in chicken BF. BPA administration also lessened the expression of PI3K and AKT and promoted HSPs (HSP27, HSP40, HSP60, and HSP70) activation. whereas CIN supplementation prominently mitigated BPA-caused these changes and the apoptosis and necroptosis damages. In brief, this study illuminated that CIN could protect the chicken BF against BPA-induced apoptosis and necroptosis through restraining oxidative stress and activating PI3K/AKT pathway.