Astaxanthin mitigates the inflammatory toxicity of microcystin-LR on zebrafish embryos

Astaxanthin (AST) as a natural carotenoid exhibits potent antioxidant and anti-inflammatory capacities. This work investigated AST's protective effects against microcystin-LR (MC-LR) toxicity to zebrafish embryos. When the zebrafish embryos were exposed to a sublethal, environmentally relevant concentration of MC-LR (10 μg/L, approximately half of the LC₅₀ value), AST (100 μg/L) could significantly reduce MC-LR-induced mortality by 39.8% and deformity rates by 60.0%. Furthermore, AST decreased ROS and MDA levels by 11.0% and 14.5%, respectively, and enhanced the activities of superoxide dismutase (SOD, 4.4-fold), catalase (CAT, 1.2-fold), and glutathione reductase (GR, 1.6-fold). It also ameliorated MC-LR-induced inflammatory responses, as evidenced by a 49.1% reduction in neutral red staining, a 42.0% to 42.9% improvement in host resistance, and a significant down-regulation of major cytokines (IL-1β, IL-6, IL-8, TNF-α) by 0.4 to 0.6-fold. Analysis of the transcriptome revealed that AST can inhibit the C-type lectin receptor signaling pathway and others to counteract the inflammatory and oxidative stress induced by MC-LR. Our findings confirm that AST neutralizes the toxicity of MC-LR through the mechanisms of antagonizing oxidative stress, exhibiting anti-inflammatory and immunomodulatory effects, which may pave the way for AST being used in aquaculture and environmental health.