Abstract
Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 μg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 μg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01–100 μg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway.
Highlights
Bisphenol S (BPS) is an emerging environmental contaminant commonly used as an alternative for bisphenol A (BPA) in the manufacturing of polycarbonate plastic, thermal paper, and numerous consumer products.[1,2]
This study provides potential phenotypespecific biomarkers through linking differentially expressed genes (DEGs) to toxicity endpoints, which could be useful in ecological risk assessments of BPS
No significant differences between nominal and measured concentrations were detected (Table S6)
Summary
Bisphenol S (BPS) is an emerging environmental contaminant commonly used as an alternative for bisphenol A (BPA) in the manufacturing of polycarbonate plastic, thermal paper, and numerous consumer products.[1,2] BPS has been detected in sediments (ND−1970 ng/g dw), sewage sludge (1.79−1480 ng/g dw), surface water (ND−7.2 ng/mL), and indoor dust (0.83−25 500 ng/g) in several countries.[3−6] BPS has further been detected in human serum (ND−0.1 ng/mL), urine (ND−29.261 ng/mL), maternal sera (ND−0.07 ng/mL), and cord sera (ND−0.12 ng/mL).[7,8] The concentrations measured within environmental samples and detected in aquatic and terrestrial organisms may pose significant risks to human health and the environment.[7,8] A systematic review of 22 previous in vitro and in vivo studies including human and aquatic organisms indicated that BPS exhibited estrogenic, cytotoxic, genotoxic, and neurotoxic effects similar to or even greater than those reported following BPA exposure.[9]. Low levels of BPS-induced neurogenesis in the hypothalamus of embryonic zebrafish and influenced hyperactive behavior in the resulting larvae.[11] In addition, embryonic zebrafish exposed to 0.5−25 mg/L BPS exhibited increased rates of estrogenic activity,[12] with oxidative stress and proinflammatory impacts further observed following BPS exposure in early life-stage zebrafish.[13−15] Perturbations to metabolism[16] and disruption in thyroid hormone concentrations,[17] glucose homeostasis,[18] and hematopoiesis[14] have been noted This suggests a broad-spectrum of BPS mechanisms and increased risk of BPS toxicity to biota. This study provides potential phenotypespecific biomarkers through linking differentially expressed genes (DEGs) to toxicity endpoints, which could be useful in ecological risk assessments of BPS
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