Nitrate induced hepatic fibrosis in tadpoles of Bufo gargarizans by mediating alterations in toll-like receptor signaling pathways.

The nitrate pollution has become an increasingly serious environmental problem worldwide, and the toxic effects of elevated nitrate levels in the environment on aquatic animals remain to be elucidated. The purpose of the present study was to investigate the mechanisms of liver injury to tadpoles after exposure to nitrate from embryonic to metamorphic climax and to assess the recovery process of liver function after cessation of exposure. In the group with continuous nitrate exposure, the livers and thyroid of tadpoles showed remarkably histological lesions, of this with structural disorganization of the hepatocytes, cellular atrophy, and fibrosis, as well as significant reduction in the follicular and colloidal area of the thyroid. Meanwhile, the expression levels of genes related to inflammatory signaling pathways, such as TLR2, TLR6 and NF-κB, were significant elevated. After termination of exposure at Gs23, liver damage (histologic, ultrastructural, and molecular levels) was almost completely recovered, whereas thyroid gland damage was irreversible. Overall, this study shed light on the harmful effects of nitrate pollution on amphibian health and emphasizes the importance of controlling nitrate emissions in the environment.