Artemether attenuates renal tubular injury by targeting mitochondria in adriamycin nephropathy mice.

Chronic kidney disease (CKD) is complex and current treatment remains limited. As we know, glomerular injury plays a dominant role in kidney disease progression. However, accumulating evidence demonstrated that renal tubules, rather than being victims or bystanders, are major initiators in renal fibrosis progression. Renal tubules are rich in mitochondria and mitochondrial dysfunction may participate in renal tubular phenotypic changes and ultimately promote renal fibrosis. Previous studies have proved that artemether displayed renal protective effects, but the mechanisms remain unclear. In this experiment, we showed that artemether reduced urinary protein/creatinine ratio and attenuated renal tubular injury. Both in vivo and in vitro results indicated that artemether could restore renal tubular phenotypic alterations. Meanwhile, the unbalanced expressions of Bax and Bcl-xL in renal tubules were restored by artemether. In addition, artemether also regulated mitochondrial pyruvate metabolism, increased mitochondrial biogenesis, and improved mitochondrial function. Taken together, this study suggested that artemether could attenuate renal tubular injury by regulating mitochondrial biogenesis and function. It has great potential to be translated to the clinic as a therapeutic agent for treating kidney diseases, especially those associated with renal tubular injury. AJTR