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Remogliflozin attenuates thioacetamide-induced nephrotoxicity: association with Nrf2/HO-1, SIRT1/AMPK, and TLR4/NF-κB

Marwa Qadri1,2, Daniyah A Almarghalani3,4, Abdulaziz Alarifi5,6

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.

Toxicology Mechanisms and Methods
|August 13, 2026
PubMed

Insights

Remogliflozin, an SGLT2 inhibitor, showed potential in protecting against thioacetamide-induced renal injury in rats by reducing oxidative stress and inflammation. Further preclinical studies are warranted to confirm these renoprotective effects.

Area of Science:

  • Nephrology
  • Pharmacology
  • Biochemistry

Background:

  • Thioacetamide (TAA) is a known inducer of renal injury, primarily through mechanisms involving oxidative stress and inflammation.
  • Sodium-glucose cotransporter 2 (SGLT2) inhibitors, like remogliflozin, have demonstrated renoprotective properties in various preclinical models.
  • Understanding the molecular pathways modulated by SGLT2 inhibitors in TAA-induced nephropathy is crucial for therapeutic development.

Purpose of the Study:

  • To evaluate the renoprotective effects of remogliflozin in a rat model of thioacetamide-induced renal injury.
  • To investigate the impact of remogliflozin on oxidative stress, inflammation, and key signaling pathways involved in renal damage.
  • To assess the dose-dependent effects of remogliflozin on renal function and histopathology.

Main Methods:

  • Male Wistar rats were administered thioacetamide to induce renal injury.
  • Animals were treated with remogliflozin at doses of 25 mg/kg or 50 mg/kg daily.
  • Renal function, oxidative stress markers (GSH, SOD, MDA), antioxidant/inflammatory mediators (Nrf2, HO-1, TLR4/NF-κB, TNF-α, IL-1β), and metabolic/kinase biomarkers (SIRT1, AMPK, PI3K, AKT) were assessed. Histopathology and immunohistochemistry were also performed.

Main Results:

  • Remogliflozin treatment was associated with improved renal function, indicated by lower serum creatinine, urea, and uric acid levels.
  • Significant modulation of biomarkers was observed, including increased renal Nrf2, HO-1, SIRT1, and p-AMPK, and decreased MDA, TLR4, NF-κB, TNF-α, IL-1β, PI3K, and AKT.
  • Histopathological analysis revealed reduced tissue injury, decreased mTOR and MYD88 immunoreactivity, and enhanced Nrf2 staining in remogliflozin-treated groups.

Conclusions:

  • Remogliflozin demonstrated significant renoprotective effects in the thioacetamide-induced renal injury model in rats.
  • The protective mechanisms appear to involve the attenuation of oxidative stress and inflammation, alongside the modulation of key cellular signaling pathways.
  • These findings support further preclinical investigation of remogliflozin for TAA-associated renal injury, although causal mechanisms require confirmation.
Keywords:
Nrf2Remogliflozinnephrotoxicityoxidative stressthioacetamide

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