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Inhibition of Ferroptosis Attenuates Acute Kidney Injury in Rats with Severe Acute Pancreatitis

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Abstract

Background

Acute kidney injury (AKI) is a frequent complication of severe acute pancreatitis (SAP). Ferroptosis is involved in a range of diseases. However, the role of ferroptosis in SAP-induced AKI has yet to be elucidated.

Aims

We aimed to investigate whether ferroptosis is induced in the kidney after SAP and whether inhibition of ferroptosis ameliorates AKI in a rat model of SAP.

Methods

Sodium taurocholate (5%) was retrogradely perfused into the biliopancreatic duct to establish a model of SAP with AKI in rats. The levels of serum amylase, lipase, tumor necrosis factor (TNF)-α, interleukin (IL)-6, creatinine (Cr) and blood urea nitrogen (BUN) in rats were measured. We also determined the biochemical and morphological changes associated with ferroptosis in renal tissue, including iron accumulation, lipid peroxidation assays, and mitochondrial shrinkage. H&E staining was used to assess pancreatic and renal histological changes. Western blot analysis, RT-PCR, and immunofluorescence staining were performed to analyze the expression of ferroptosis-related proteins and genes.

Results

SAP-induced AKI was followed by iron accumulation, increased lipid peroxidation, and upregulation of ferroptosis-related proteins and genes. Twenty-four hours after SAP, TEM confirmed the presence of typical shrunken mitochondria. Furthermore, treatment with liproxstatin-1 lowered the levels of serum amylase, TNF-α, IL-6, Cr and BUN, decreased kidney lipid peroxidation and alleviated pancreatic and renal histopathology injury in SAP rats.

Conclusion

Our findings are the first to demonstrate the involvement of ferroptosis in SAP-associated renal damage and present ferroptosis as a therapeutic target for effective treatment of SAP-induced AKI.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China Grant Nos. 81270448 and 81470890.

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Authors and Affiliations

  1. Center of Colon and Rectum, Qingdao Municipal Hospital, Qingdao University, No. 1 Jiaozhou Road, Qingdao, 266011, Shandong Province, China

    Deliang Ma, Chang Li, Yingjian Jiang, Jiang Wang & Dianliang Zhang

  2. Breast Surgery, Qingdao Municipal Hospital, Qingdao University, No. 1 Jiaozhou Road, Qingdao, 266011, Shandong Province, China

    Pengling Jiang

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  1. Deliang Ma
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Ma, D., Li, C., Jiang, P. et al. Inhibition of Ferroptosis Attenuates Acute Kidney Injury in Rats with Severe Acute Pancreatitis. Dig Dis Sci 66, 483–492 (2021). https://doi.org/10.1007/s10620-020-06225-2

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  • DOI: https://doi.org/10.1007/s10620-020-06225-2

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