Objectives: Renal tubular injury plays an important role in the progression of diabetic kidney disease. Previous studies demonstrated that artemether, an antimalarial agent, exerts renal tubular protection in diabetes. However, the detailed mechanisms remain unclear. Several studies have indicated that disorders of iron metabolism have a great impact on renal tubular injury. Therefore, this study was performed to explore whether the therapeutic effects of artemether on diabetic renal tubular injury are related to iron metabolism.
Methods: Male C57BL/6 J mice were randomly divided into three groups. Mice in the type 1 diabetic (T1D) control and streptozotocin (STZ) groups were fed a regular diet; mice in the STZ plus artemether (STZ+Art) group were treated with artemether.
Results: Artemether significantly reduced the urinary albumin:creatinine ratio and tubular injury in mice with T1D. Artemether also restored the energy imbalance and restored the changes of mitochondrial cristae in mice with T1D. Increased protein and mRNA levels of ferritin heavy chain (FTH) and ferritin light chain (FTL) were observed in renal tubules of diabetic mice. In response to iron overload, levels of iron transport-related proteins and the antioxidant system related to iron metabolism were abnormal in diabetic mice. Artemether significantly restored the protein and mRNA expression levels of both FTH and FTL. Both the iron transport and antioxidant systems were also restored by artemether to varying degrees.
Conclusions: Artemether attenuates renal tubular injury in diabetic mice; this effect might be related to its regulation of iron metabolism.
Keywords: Iron overload; mitochondria; tubular injury; type 1 diabetes.
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