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Antibiotics are emerging environmental contaminants with wide attention due to their high consumption and pseudo-persistence in the environment. They have been shown to induce obesity or obesity-related metabolic diseases in experimental animals, but the underlying toxicological mechanisms remain unclear. Here, the disruptive effects of four commonly used antibiotics, namely doxycycline (DC), enrofloxacin (ENR), florfenicol (FF) and sulfamethazine (SMT) on lipid metabolism were investigated in zebrafish (Danio rerio) larvae and murine preadipocyte cell line. Triglyceride (TG) content was reduced after 1 ng/L DC or ENR exposure but was increased at higher concentrations up to 100 mg/L. FF increased and SMT reduced TG content but did not show any concentration dependence. None of the antibiotics had any significant effect on total cholesterol (TC) content in zebrafish except 100 μg/L SMT. Expression levels of 8 lipid metabolism-related genes were also quantified. SMT was most disruptive by up-regulating six genes, followed by FF which up-regulated four genes and down-regulated one gene, whereas DC and ENR both up-regulated one gene. In 3T3-L1 preadipocytes, ENR, FF, and SMT in general increased TG content, while 100 mg/L FF reduced TG substantially. DC did not show any effect up to 10 mg/L, at which TG increased significantly. FF and SMT increased TC slightly at low concentrations but reduced it at high concentrations, whereas TC, DC and ENR had no effect at any tested concentrations. Gene expression measurement also indicated that SMT was most disruptive, followed by FF, DC, and ENR. Reporter gene assays showed that only SMT inhibited the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ). The above experimental results and clustering analysis demonstrate that the four antibiotics exerted disruption on lipid metabolism through different mechanisms, and one of the mechanisms for SMT may be inhibition of PPARγ transcriptional activity.

As alternatives to perfluorooctanoic acid (PFOA), hexafluoropropylene oxide (HFPO) homologues, including hexafluoropropylene oxide dimer acid (HFPO-DA), hexafluoropropylene oxide trimer acid (HFPO-TA), and hexafluoropropylene oxide tetramer acid (HFPO-TeA), have attracted widespread attention recently due to their environmental ubiquity and high potential for bioaccumulation and toxicity. In the present study, a set of in vivo mouse and in vitro mouse testicular Sertoli TM4 cell experiments were employed to explore the male reproductive toxicity and underlying mechanisms of HFPO homologues on blood-testis barrier. Tissue and permeability analyses of mice testes after 28-day treatment with 5 mg/kg/day HFPO-DA or PFOA, or 0.05 mg/kg/day HFPO-TA or HFPO-TeA indicated that there was an increase in the degradation of TJ protein occludin in mice with a disrupted blood-testis barrier (BTB). Following exposure to 100 μM HFPO-DA, HFPO-TA or 10 μM PFOA, HFPO-TeA, transepithelial electrical resistance measurements of TM4 cells also indicated BTB disruption. Additionally, as a result of the exposure, matrix metalloproteinase-9 expression was enhanced through activation of p38 MAPK, which promoted the degradation of occludin. On the whole, the results indicated HFPO homologues and PFOA induced BTB disruption through upregulation of p-p38/p38 MAPK/MMP-9 pathway, which promoted the degradation of TJ protein occludin and caused the disruption of TJ.