Protective effect of combining wickerwork and fluconazole against Candida albicans infection in obese mice
OBJECTIVE To explore the adverse consequences of obesity plus Candida albicans(CA)infection and examine the therapeutic effect of fluconazol(FLC)in combination with piperlonguminine(GBN).METHODS A model of high-fat diet(HFD)obese mice plus invasive Candida albicans infection was constructed.Different drugs were dosed.Death,organ mass,renal load and renal histopathological morphology were detected.The serum levels of triglyceride(TG),total cholesterol(TC),low-density lipoprotein-C(LDL-C)and high-density lipoprotein-C(HDL-C)were measured.And the levels of neutrophil extra-cellular traps(NETs)in intraperitoneal lavage fluid were quantified,as well as the expressions of inflammatory factors transform-ing growth factor-beta(TGF-β),interleukin-6(IL-6),monocyte chemotactic protein-1(MCP-1)and keratinocyte-derived che-mokine(KC)in renal tissues.In vitro assays were performed using all-trans retinoic acid(ATRA)for inducing differentiation of HL-60 cells into neutrophil-like granulocytes(dHL-60).dHL-60 cells were pre-treated with GBN and stimulated by phorbol ester(PMA).The intracellular levels of reactive oxygen species(ROS)and NETs were detected.RESULTS Obese mice infected with CA had dramatically lower survival,elevated renal load and higher levels of lipids and NETs.FLC in combination with GBN restored survival to 100％in obese infected mice and improved visceral indices,while further reducing renal load,lip-ids,inflammatory factors and NETs.In vitro results indicated that GBN reduced the levels of reactive oxygen species(ROS)and NETs generated by PMA-stimulated neutrophils.CONCLUSION CA infection in obese mice is associated with higher mortality and severe inflammatory response in vivo.GBN regulates the inflammatory state through suppressing ROS production and NETs release from neutrophils and ameliorates infection in obese mice in combination with FLC.
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