E. adenophorum induces Cell Cycle Arrest and Apoptosis of Splenocytes through the Mitochondrial Pathway and Caspase Activation in Saanen Goats

Abstract

The precise cytotoxicity of E. Adenophorum in relation to the cell cycle and apoptosis of splenocytes in Saanen goats remains unclear. In the present study, 16 Saanen goats were randomly divided into four groups, which were fed on 0%, 40%, 60% and 80% E. adenophorum diets. The results of TUNEL, DAPI and AO/EB staining, flow cytometry analysis and DNA fragmentation assays showed that E. adenophorum induced typical apoptotic features in splenocytes, suppressed splenocyte viability, and caused cell cycle arrest in a dose-dependent manner. However, westernblot, ELISA, qRT-PCR and caspase activity analyses showed that E. adenophoruminhibited Bcl-2 expression, promoted Bax translocation to the mitochondria, triggered the release of Cytc from the mitochondria into the cytosol, and activated caspase-9 and -3 and the subsequent cleavage of PARP. Moreover, in E. adenophorum-induced apoptosis, the protein levels of Fas, Bid, FasL and caspase-8 showed no significant changes. E. adenophorum treatment induced the collapse of ΔΨm. Moreover, these data suggested that E. adenophorum induces splenocyte apoptosis via the activation of the mitochondrial apoptosis pathway in splenocytes. These findings provide new insights into the mechanisms underlying the effects of E. adenophorum cytotoxicity on splenocytes.

Ageratina adenophora induces mice hepatotoxicity via ROS-NLRP3-mediated pyroptosis

“…Previous studies showed that the ingestion of A. adenophora as a feed additive induced hepatotoxicity in mice 28 and rat 7 , as well as chronic pulmonary disease in horses 29 . In our previous studies, apoptosis pathway was triggered by A. adenophora in goat and mice 10 , 30 , 31 . In this study, IL-1β, a pro-inflammatory cytokine, was induced by A. adenophora (Fig.…”

Metabolomics profiles delineate uridine deficiency contributes to mitochondria-mediated apoptosis induced by celastrol in human acute promyelocytic leukemia cells

“…For detection of cell apoptosis, FITC Annexin V Apoptosis Detection Kit I (BD Pharmingen, NJ, USA) was used and performed according to the manufacturer's instruction and more details were according to the previous study [45]. …”

Degradation of euptox A by tannase-producing rumen bacteria from migratory goats

“…The pollen grains and volatile metabolites cause respiratory problems in humans, and digestive problems in susceptible animals. Its allelopathic competition with other plants is a major cause of loss to agriculture and native plant diversity (Liao et al 2014;He et al 2015).…”

“…The plant is originally native to Mexico, but at present it has spread in many parts of the world. It contains hepatotoxic 9-oxo-10,11-dehydroageraphorone (also called euptox A) and pyrrolidizine alkaloids that cause pulmonary toxicity (pulmonary interstitial fibrosis, emphysema and alveolar epithelisation) in equine (Oelrichs et al 1995), cell cycle arrest, apoptosis in splenocytes, suppressed splenocyte viability and various health problems (Bhardwaj et al 2001;Liao et al 2014;He et al 2015).…”