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Kidney Week

Abstract: PO0445

Mechanisms of Aristolochic Acid I (AAI)-Induced Proximal Tubule Cell Injury

Session Information

  • AKI: Novel Insights
    November 04, 2021 | Location: On-Demand, Virtual Only
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Upadhyay, Rohit, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Batuman, Vecihi, Tulane University School of Medicine, New Orleans, Louisiana, United States
Background

Aristolochic acids (AAs) are naturally occurring polyaromatic nitrogen compounds extracted from certain plants that were used to treat various diseases for centuries until their nephrotoxicity and carcinogenicity began to be recognized. Aristolochic acid I (AAI) is potentially one of the main pathogenic compounds and has been demonstrated to have nephrotoxic, carcinogenic, and mutagenic effects. Previous studies have indicated that AAI acts mainly on proximal renal tubular epithelial cells however investigation into the mechanisms of AAI-induced proximal tubule cell damage are still warranted.

Methods

Human kidney proximal tubule cells (PTCs; HK2 cell line) were exposed to AA1 at different time/dose conditions in vitro. Cell proliferation, ROS generation, NO production, m-RNA/ protein expressions and mitochondrial dysfunction was checked in HK2 cells after treating them with AA1.

Results

We found that AA1 treatment decreased HK2 cell proliferation significantly at 24hrs with 40μM concentration. AA1 exposure increased ROS generation and decreased NO production significantly. Furthermore, gene/ protein expression studies demonstrated activation of innate immunity (TLRs 2,3, 4 and 9, HMGB1), inflammatory (TNFA, IL6, IL18 and TGFB) and kidney injury (LCN2, KIM1) markers. In addition, our results indicated AA1 induced epithelial-mesenchymal transition (EMT) as well as mitochondrial dysfunction in HK2 cells.

Conclusion

AA1 treatment caused injury to proximal tubule cells (HK2) through ROS-HMGB1/mt DNA mediated TLRs activation and inflammatory response.