Abstract
Increasing evidences have demonstrated that Ageratina adenophora (A. adenophora) can cause hepatotoxicity of animals. Liver is an important site in immune regulation and inflammatory responses. However, the information about hepatotoxicity induced by A. adenophora in relation to inflammation is still finite. To investigate the underlying mechanism, we conducted animal experiments with different dosage of A. adenophora. Mice were randomly divided into 4 groups and administrated with 0%, 10%, 20% and 30% levels of A. adenophora pallet diet in control, group A, B and C, respectively. The results showed that A. adenophora caused hepatotoxicity as revealed by increasing alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase. Then, the reactive oxygen species (ROS) levels were shown to be elicited by A. adenophora through flow cytometry assay in a dose-dependent manner. Furthermore, pyroptosis was activated by A. adenophora, which was characterized by increasing protein and mRNA levels of caspase-1, gasdermin D and interleukin-1β. Notably, ROS down-stream factors, including nod-like receptor inflammasome protein 3 and nuclear factor-κB, were also activated by A. adenophora. These data demonstrated that A. adenophora caused liver inflammatory injury and induced hepatocyte pyroptosis by activating NLRP3 inflammasome, which was triggered by elevating ROS production levels. This research might provide new insights into the mechanism of hepatotoxicity induced by A. adenophora.
Highlights
Ageratina adenophora (A. adenophora, called as Eupatorium adenophorum), originating from Mexico, is a perennial semi-shrubby herbaceous plant, which has successfully invaded into many countries[1]
Basing on our previous study and the toxicological effects of A. adenophora, we hypothesized that pyroptosis induced by Reactive oxygen species (ROS)-mediated NLRP3 activation pathway might play a fundamental role in the process of hepatotoxicity induced by A. adenophora in mice hepatocytes
The results showed that HSI in the A. adenophora administrated groups were all remarkably higher than that in the control group (Fig. 1b), indicating obvious hepatomegaly caused by A. adenophora
Summary
Ageratina adenophora (A. adenophora, called as Eupatorium adenophorum), originating from Mexico, is a perennial semi-shrubby herbaceous plant, which has successfully invaded into many countries[1]. A. adenophora is troublesome specie in the invasive areas, which can encroach on grass and cause livestock poisonings, including acute asthma, diarrhea, depilation, even death[6]. Previous studies have demonstrated that pyroptosis is emerging as a ubiquitous immune effector in a variety of cells[18,21]. It can be triggered by various infections and non-infections stimulates[22]. Basing on our previous study and the toxicological effects of A. adenophora, we hypothesized that pyroptosis induced by ROS-mediated NLRP3 activation pathway might play a fundamental role in the process of hepatotoxicity induced by A. adenophora in mice hepatocytes
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