Characterization of zearalenone-induced hepatotoxicity and its mechanisms by transcriptomics in zebrafish model.

Zearalenone is a mycotoxin produced by several species of Fusarium fungi, which contaminates crop and cereal products worldwide. It is widely distributed and can be transported from agricultural fields to the aquatic environment via soil run-off. Zearalenone exposure can cause serious health problems to humans and animals, including estrogenic, immunotoxic, and xenogenic effects. Though its hepatotoxicity has been reported by few studies, the underlying mechanisms are yet to be investigated. This study aimed to comprehensively evaluate the hepatotoxic effects of zearalenone and its molecular mechanism in the zebrafish model system. First, we found zearalenone exposure can cause liver injury, as evidenced by reduced liver size, decreased liver-specific fluorescence, increased aspartate aminotransferase (AST) activity, delayed yolk sac absorption and lipid accumulation. Then, RNA sequencing (RNA-seq) was performed using dissected zebrafish fry liver, which found genes involved in oxidation and reduction were significantly enriched. Quantitative real-time PCR further confirmed the dysregulated expression of several antioxidant enzymes. Additionally, lipid peroxidation was proved by increased malondialdehyde (MDA) production and gene expression at the mRNA level. In contrast to the previous study, apoptosis was likely decreased in response to zearalenone exposure. Last, glucuronidation and amino acid metabolism were also disrupted by zearalenone. Our results revealed the complex mechanism of zearalenone-induced hepatotoxicity, which is a valuable contribution to a more comprehensive understanding of the toxicity of zearalenone.

Sodium humate alters the intestinal microbiome, short-chain fatty acids, eggshell ultrastructure, and egg performance of old laying hens.

This study investigated the effect of sodium humate supplementation on changes in the intestinal microbiome, intestinal short-chain fatty acids production, and trace element absorption in older laying hens, with consequent effects on egg performance and shell quality. We used the same hens as their own control; a total of 720 laying hens aged 422 days were randomly divided into three replicates, with the CON group fed a commercial diet at 422-441 days of age and the HANa group fed a commercial diet supplemented with 0.05% sodium humate at 442-461 days of age. Compared with the CON group, in the HANa group, Bacteroidetes and Actinobacteria were significantly increased, whereas, Firmicutes was significantly decreased. Further, Veillonella, Enterococcus, Lactobacillus, and Turricibacter significantly decreased, and Peptoniphilus, Helcococcus, GW-34, Psychrobacter, Anaerococcus, Corynebacterium, Facklamia, Trichococcus, Gallicola, Clostridium, and Oscillospira were significantly increased. The results showed that sodium humate significantly altered the alpha and beta diversity and changed the structure of the intestinal microbiome. Acetic acid, isovaleric acid, and isobutyric acid, among short-chain fatty acids were significantly increased in the HANa group, whereas trace elements such as Mn, Zn, and Fe were significantly reduced. The eggshell strength and ultrastructure were significantly altered. In this study, sodium humate was found to alter the intestinal microbiome structure of aged hens, change the production of short-chain fatty acids, and promote the absorption of trace elements to keep aged hens from experiencing a decrease in egg production performance.

Inflammation aggravated the hepatotoxicity of triptolide by oxidative stress, lipid metabolism disorder, autophagy, and apoptosis in zebrafish.

Triptolide is a major compound isolated from the Tripterygium wilfordii Hook that is mainly used for the treatment of autoimmune disorders and inflammatory diseases. Though triptolide-induced hepatotoxicity has been widely reported, the hepatic effects when the patients are in an inflammatory state are not clear. In this study, we used low-dose Lipopolysaccharides (LPS) to disrupt the inflammation homeostasis in the liver of zebrafish and explored the hepatotoxicity of triptolide under an inflammatory state. Compared with the Triptolide group, LPS-Triptolide cotreatment exacerbate the liver injury with a remarkable decrease of liver size and liver-specific fluorescence intensity, accompanied by significant elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Liver cell damages were further demonstrated by histological staining and scanning electron microscopy observation. Lipid metabolism was severely impaired as indicated by delayed yolk sac absorption, accumulated triglycerides in the liver, and dysregulation of the related genes, such as ppar-α, cpt-1, mgst, srebf1/2, and fasn. Oxidative stress could be involved in the molecular mechanism as the Nrf2/keap1 antioxidant pathways were down-regulated when the zebrafish in an inflammatory state. Moreover, the expression of autophagy-related genes such as beclin, atg5, map1lc3b, and atg3 was also dysregulated. Finally, apoptosis was significantly induced in responses to LPS-Triptolide co-treatment. We speculate that triptolide could exacerbate the immune response and impair lipid metabolism, resulting in enhanced sensitivity of the zebrafish liver to triptolide-induced toxic effects through disruption of the antioxidant system and induction of apoptosis.