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Canagliflozin Improves Liver Function in Rats by Upregulating Asparagine Synthetase

Shiqi Wang1, Yasong Ding1, Ruoyao Dong1

  • 1Department of Pharmaceutics, School of Pharmacy, China Medical University, Shenyang, China.

Pharmacology
|September 13, 2021
PubMed
Abstract

Insights

Canagliflozin reduces liver injury in rats by activating the AMPK/Nrf2/ATF4 pathway, which increases asparagine synthetase expression. This suggests potential benefits for diabetic patients with liver issues.

Area of Science:

  • Hepatology
  • Pharmacology
  • Biochemistry

Background:

  • Canagliflozin (CANA), a sodium-glucose cotransporter 2 inhibitor, is used for diabetes treatment, but its liver effects are unclear.
  • Asparagine synthetase (ASNS) function in liver injury is uncharacterized.
  • This study explores CANA's hepatoprotective role and its link to ASNS in a rat model.

Purpose of the Study:

  • To investigate the hepatoprotective effect of canagliflozin (CANA) in a rat liver injury model.
  • To elucidate the underlying molecular mechanisms involving asparagine synthetase (ASNS).
  • To assess the potential of CANA for patients with type 2 diabetes and impaired liver function.

Main Methods:

  • A rat model of liver injury was induced using carbon tetrachloride.
  • Rats received daily oral CANA for 8 weeks.
  • Liver injury markers (ALT, AST, LDH), histopathology, and protein expression (Western blotting) were analyzed.

Main Results:

  • CANA treatment significantly reduced serum ALT, AST, and LDH levels, indicating diminished liver injury.
  • CANA activated AMP-activated protein kinase (AMPK), promoting Nrf2 and ATF4 nuclear translocation.
  • This activation led to upregulated ASNS expression in the injured livers.

Conclusions:

  • Canagliflozin demonstrates significant hepatoprotective effects in a rat model.
  • The mechanism involves activation of the AMPK/Nrf2/ATF4 signaling pathway and subsequent ASNS upregulation.
  • CANA shows promise for managing liver dysfunction in patients with type 2 diabetes.
Keywords:
AMP-activated protein kinaseAsparagine synthetaseCanagliflozinLiver injuryNuclear factor erythroid 2-related factor 2

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