The mitochondrial and endoplasmic reticulum pathways involved in the apoptosis of bursa of Fabricius cells in broilers exposed to dietary aflatoxin B1

Abstract

Aflatoxin B₁ (AFB₁), a toxic metabolite produced by some fungi, exerts well-known hepatocarcinogenic and immunosuppressive effects, the latter can increase the apoptotic immune cells in vitro. However, it is largely unknown that which signaling pathways contribute to excessive apoptosis of immune cells which induced by AFB₁. In this study, we investigated the roles of the mitochondria, endoplasmic reticulum (ER) and death receptor activated apoptotic pathways in the bursal of Fabricius (BF) cells in the broilers exposed to AFB₁ diet. We found that (1) AFB₁ diet induced morphological changes in the BF. (2) FCM and TUNEL methods showed that excessive apoptosis could be resulted from AFB₁ intake. (3) AFB₁-induced apoptosis of bursal cells involved mitochondrial pathway (increase of Bax, Bak, cytC, caspase-9, Apaf-1, caspase-3 and decrease of Bcl-2 and Bcl-xL) and ER pathway (increase of Grp78/Bip, Grp94 and CaM). (4) Oxidative stress was confirmed in the BF of chicken fed on AFB₁ diet. Overall, this work is the first to demonstrate that the activation of mitochondria and ER apoptosis pathways can lead to excessive apoptosis in BF cells, and oxidative stress is a crucial driver during AFB₁ exposure.