Developmental toxicity by thifluzamide in zebrafish (Danio rerio): Involvement of leptin

Abstract Although previous trials have indicated that thifluzamide induces developmental inhibition in zebrafish, understanding the distinct mechanism of thifluzamide in this process remains challenging. This study investigated the effect of thifluzamide on zebrafish development and the underlying related signaling pathway. Thifluzamide repressed glucagon (GC) levels but increased growth hormone (GH) levels, and changed the expression of the genes related to growth and development. Additionally, protein kinase A (PKA) and leptin levels were obviously decreased in zebrafish after exposure to thifluzamide for 28 days, but the phosphorylation of cAMP responsive element-binding protein (CREB) was increased. Our results suggested that the anti-developmental effects of thifluzamide in zebrafish are largely associated with alterations in expressions of genes related to growth and development through modulation of leptin.