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Inhibition of Caspase-11-Mediated Pyroptosis Alleviates Acute Kidney Injury Associated with Severe Acute Pancreatitis

Yang Shao1,2, Chang Li2, Yingjian Jiang2

  • 1Qingdao Medical College, Qingdao University, Qingdao, Shandong Province, China.

Journal of Investigative Surgery : the Official Journal of the Academy of Surgical Research
|November 9, 2022
PubMed

Insights

Caspase-11-mediated pyroptosis contributes to acute kidney injury (AKI) in severe acute pancreatitis (SAP). Inhibiting this process with wedelolactone improved kidney function and reduced inflammation in a rat model, suggesting a new treatment strategy.

Area of Science:

  • Nephrology
  • Gastroenterology
  • Immunology

Background:

  • Acute kidney injury (AKI) frequently complicates severe acute pancreatitis (SAP).
  • The role of caspase-11-mediated pyroptosis in SAP-induced AKI is not well understood.
  • Pyroptosis is a key inflammatory cell death pathway implicated in various diseases.

Purpose of the Study:

  • To investigate the involvement of caspase-11-mediated pyroptosis in SAP-induced AKI.
  • To determine if inhibiting caspase-11-mediated pyroptosis can ameliorate SAP-induced AKI.
  • To explore potential therapeutic targets for SAP-induced AKI.

Main Methods:

  • A rat model of SAP-induced AKI was established using sodium taurocholate.
  • Wedelolactone, a caspase-11 inhibitor, was administered at 1 and 6 hours post-SAP induction.
  • Serum markers (amylase, lipase, IL-6, BUN, TNF-α, Cr), pyroptosis proteins (caspase-11, GSDMD), and cytokines (IL-1β, IL-18) were measured.
  • Histopathological analysis of pancreas and kidney tissues was performed.

Main Results:

  • SAP induction significantly elevated serum biochemical markers and pyroptosis-related proteins in kidney tissues.
  • Wedelolactone treatment reduced pyroptosis markers, inflammatory cytokines, and serum levels of lipase, amylase, IL-6, TNF-α, BUN, and Cr.
  • Histopathological examination revealed amelioration of renal and pancreatic damage in wedelolactone-treated rats.

Conclusions:

  • Caspase-11-mediated pyroptosis plays a significant role in the pathogenesis of SAP-induced AKI.
  • Inhibition of caspase-11-mediated pyroptosis demonstrates therapeutic potential for SAP-induced AKI.
  • Targeting caspase-11 offers a promising novel treatment strategy for this condition.
Keywords:
acute kidney injurycaspase-11pyroptosissevere acute pancreatitiswedelolactone

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