Metabolomics provides insights into the alleviating effect of dietary Caulerpa lentillifera on diquat-induced oxidative damage in zebrafish (Danio rerio) liver

Excessive reactive oxygen species can induce aquatic animals under oxidative stress, which is implicated in various types of liver problems. Caulerpa lentillifera, a tropical macroalga, has good antioxidant property, and it might exert mitigating benefits on oxidative damage in fish liver. This study assessed the protective role of C. lentillifera supplementation against oxidative toxicity in liver of zebrafish induced by diquat and analyzed the potential physiological mechanisms. Fish (N = 400) were divided into four groups for 56 days. The normal control and diquat-exposed groups were both fed on a basal diet. The two other treatment groups had dietary supplementation with 20 and 50 g·kg−1C. lentillifera while exposed to diquat, respectively. Growth performances, biochemical parameters, histopathology, liver metabolomics alterations, and the mRNA expression of related genes were assessed. The outcomes revealed that diquat exposure inhibited weight gain; reduced superoxide dismutase activity; and induced noticeable augmented levels of liver malondialdehyde, alanine aminotransferase, aspartate aminotransferase, triglycerides, and blood glucose. Furthermore, marked histopathological lesions in zebrafish liver were detected. A metabolomics analysis based on liquid chromatography-mass spectrometry showed that exposure to diquat caused metabolite changes compared with the normal control fish. The down-regulated target of rapamycin (tor), protein kinase B (akt) and glucose transporter 2 (glut2) mRNAs were expressed in the liver injured by diquat. The dietary intervention with C. lentillifera restored the reduction in the growth, revealed a noticeable modulation in biochemical parameters, and recovered the histopathology. The group treated with 50 g·kg−1C. lentillifera distinguished metabolic profile from the diquat-exposed group and approached the normal control one. C. lentillifera reversed the changes in diquat exposure on 14 metabolites, which were probably related to tryptophan metabolism, cysteine and methionine metabolism, steroid hormone biosynthesis, amino sugar and nucleotide sugar metabolism and arachidonic acid metabolism. The downregulated genes produced by diquat were recovered by adding C.lentilifera to the diet. In summary, supplementation with C. lentillifera can help reduce the negative effects of oxidative stress on zebrafish liver. The current study provides clues to facilitate the understanding of oxidative damage in fish liver and suggest t