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Astragaloside IV prevents acute kidney injury in two rodent models by inhibiting oxidative stress and apoptosis pathways

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Abstract

Oxidative stress and apoptosis play key role in the pathogenesis of acute kidney injury (AKI). We hypothesize that Astragaloside IV(AS-IV) prevents AKI through inhibiting oxidative stress and apoptosis. The rats were divided into sham control, saline-,vehicle-, or AS-IV-treated groups. AS-IV (20 mg/kg) was orally administered once daily to the rats for 7 consecutive days before terminating the experiments. In ischemia-induced AKI model, experimental rats were subjected to bilateral clamping of the renal arteries for 45 min, followed by reperfusion for 24 h. In contrast-induced AKI model, iopamidol (2.9 g iodine/kg) was administered intravenously into the rats. Renal function, histopathology, oxidative stress and apoptosis were evaluated in these models. Pretreatment with AS-IV significantly decreased blood urea nitrogen, serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin levels, as well as urinary kidney injury molecule-1 level and tubular injury. AS-IV also reduced oxidative stress and tubular cell apoptosis. The p38 mitogen-activated protein kinase phosphorylation and caspase-3 activity were elevated in kidney tissues from AKI rats, accompanied by an increase in Bax expression and a decrease in Bcl-2 expression at mRNA and protein levels. These changes were prevented by AS-IV pretreatment. Therefore, AS-IV can be developed as a novel therapeutic approach to prevent AKI through targeting inhibition of oxidative stress and apoptosis pathways.

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Acknowledgments

This work was supported, in part, by grants from National Natural Science Foundation of China, No.81000305 (To Dingkun Gui) and No.30901888 (To Jianhua Huang).

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Authors and Affiliations

  1. Department of Nephrology and Rheumatology, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China

    Dingkun Gui, Yongping Guo, Wenzhen Xiao & Niansong Wang

  2. Institute of Integrated Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, China

    Jianhua Huang

  3. Department of Gastroenterology, No 1 Hospital of Chenzhou, Chenzhou, China

    Wei Liu

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  1. Dingkun Gui
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  2. Jianhua Huang
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  3. Wei Liu
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  4. Yongping Guo
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  5. Wenzhen Xiao
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  6. Niansong Wang
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Correspondence to Niansong Wang.

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Dingkun Gui and Jianhua Huang contributed equally to this work.

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Gui, D., Huang, J., Liu, W. et al. Astragaloside IV prevents acute kidney injury in two rodent models by inhibiting oxidative stress and apoptosis pathways. Apoptosis 18, 409–422 (2013). https://doi.org/10.1007/s10495-013-0801-2

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