Emodin Alleviates Lipid Accumulation and Renal Tubular Injury in Rats With DN via Inhibiting HIF-1α Expression.

BACKGROUND

Our previous study verified that lipid nephrotoxicity mediated by hypoxia-inducible factor-1 alpha (HIF-1α) activation aggravates diabetic tubular injury. This study investigated whether emodin, an inhibitor of HIF-1α, improves tubular injury by reducing lipid accumulation in diabetic tubules, and examined its underlying mechanism.

METHODS

Type 1 diabetic rats were administered 40 mg/kg emodin by gavage daily. For the in vitro study, HK-2 cells were pretreated with emodin for 6 h and then stimulated with HIF-1α activator cobalt chloride (CoCl2).

RESULTS

In vivo, emodin significantly downregulated HIF-1α protein expression in the kidneys of rats with diabetes. Emodin treatment substantially attenuated tubular pathological damage and reduced 24-h urinary total protein levels and the urinary albumin-to-creatinine ratio in rats with diabetes, accompanied by decreased expression of transforming growth factor-beta 1 (TGF-β1) and connective tissue growth factor (CTGF). Meanwhile, lipid accumulation and mitochondrial dysfunction in diabetic kidneys markedly improved after emodin treatment. Similarly, in vitro, emodin effectively reduced HIF-1α protein expression in CoCl2-treated HK-2 cells. Moreover, emodin ameliorated lipid accumulation, cellular injury, and mitochondrial homeostasis imbalance in these cells.

CONCLUSION

These data demonstrate that emodin prevents lipid accumulation and cellular injury in diabetic tubular epithelial cells, possibly by inhibiting HIF-1α activation and exerting a protective effect on mitochondria.