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Artemisinin attenuates tubulointerstitial inflammation and fibrosis via the NF‐κB/NLRP3 pathway in rats with 5/6 subtotal nephrectomy
Ist Teil von
Journal of cellular biochemistry, 2019-03, Vol.120 (3), p.4291-4300
Ort / Verlag
United States: Wiley Subscription Services, Inc
Erscheinungsjahr
2019
Quelle
Wiley Online Library - AutoHoldings Journals
Beschreibungen/Notizen
Artemisinin (Art) is isolated from Artemisia annua L. and known as the most effective antimalaria drugs. Previous studies demonstrated that it could exert an immune‐regulatory effect on autoimmune diseases. In this study, we first investigated its potential role in tubulointerstitial inflammation and fibrosis in rats with 5/6 nephrectomy. Subtotal nephrectomized (SNx) rats were orally administered Art (100 mg·kg
−1·d
−1) for 16 weeks. Blood and urine samples were collected for biochemical examination. Kidney tissues were collected for immunohistochemistry and Western blot analyses. Ang II‐induced injury of the human kidney 2 (HK‐2) cells was used for in vitro study. It was shown that Art could significantly attenuate the renal function decline in SNx rats compared with control. More importantly, Art treatment significantly reduced the tubulointerstitial inflammation and fibrosis, as demonstrated by the evaluation of renal pathology. Furthermore, Art inhibited the activation of NLRP3 inflammasome and NF‐κB in the kidneys. In in vitro study, Art pretreatment could significantly prevent the activation of NLRP3 inflammasome and NF‐κB in Ang II‐treated HK‐2 cells, while BAY11‐7082 (an inhibitor of NF‐κB) significantly inhibited Ang II‐induced NLRP3 inflammasome activation. This study suggested that Art could provide renoprotective role by attenuating the tubulointerstitial inflammation and fibrosis in SNx rats by downregulating the NF‐κB/NLRP3 signaling pathway.
We found that artemisinin (Art) treatment significantly prevents renal function decline and tubulointerstitial fibrosis in 5/6 nephrectomized rats by inhibiting NF‐κB/NLRP3 pathway. Our findings highlight the therapeutic potential of Art in preventing the progression of chronic kidney disease (CKD).