PROTECTIVE ROLE OF EMPAGLIFLOZIN AGAINST METHOTREXATE-INDUCED LIVER INJURY

Authors

  • Salahuddin Shaikh Department of Physiology, Isra University,Hyderabad, Pakistan
  • Sheraz Ansari Department of Biochemistry, Isra University,Hyderabad, Pakistan
  • Farzana Rahim Memon Department of Physiology, Isra University,Hyderabad, Pakistan
  • Farheen Malik Department of Pharmacology, Isra University,Hyderabad, Pakistan
  • Unshall Memon Department of Physiology, Isra University,Hyderabad, Pakistan
  • Anjuman Gul Memon Department of Biochemistry, College of Medicine, Qassim University, Buraydah, Kingdom of Saudi Arabia

DOI:

https://doi.org/10.69656/pjp.v22i1.1886

Keywords:

Empagliflozin, Hepatotoxicity, Liver injury, Methotrexate

Abstract

Background: Methotrexate (MTX), a commonly used chemotherapeutic and immunosuppressive agent, is associated with dose-dependent hepatotoxicity characterized by oxidative stress and liver tissue damage. Empagliflozin (EM), a sodium-glucose cotransporter-2 (SGLT2) inhibitor, has shown antioxidant properties in various organ systems. This study aimed to evaluate the hepatoprotective effects of EM against MTX-induced liver injury in rats. Methods: Forty adult Wistar rats were divided into four groups of 10 each. Group A (Control, 5% dimethyl sulfoxide as vehicle control), Group B (MTX 20 mg/Kg, i.p., on day 3), Group C (EM 10 mg/Kg/day for 7 days+MTX), and Group D (EM 30 mg/Kg/day for 7 days+MTX). Serum liver enzymes (ALT, AST), bilirubin, and oxidative stress markers (MDA, SOD, GPx, catalase) were measured. Liver tissues were also examined histologically using a semi-quantitative scoring system for cellular degradation, cytoplasmic vacuolization, sinusoidal dilatation, and inflammatory infiltration. Results: MTX administration resulted in significant elevations in ALT, AST, bilirubin, and MDA levels, along with reductions in SOD, GPx, and catalase activities (p<0.001). Histopathology confirmed severe hepatic damage in the MTX group. EM co-treatment, significantly increased antioxidant enzyme activity, reduced lipid peroxidation, and improved histological scores, with Group D showing better results (p<0.001). Biochemical and microscopic parameters showed a dose-dependent protective effect of EM. Conclusion: EM significantly attenuates MTX-induced hepatotoxicity by reducing oxidative stress and preserving liver histoarchitecture. These findings suggest a potential role for EM as a hepatoprotective agent against drug-induced liver injury.

Pak J Physiol 2026;22(1):12–5, DOI: https://doi.org/10.69656/pjp.v22i1.1886

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Published

31-03-2026

How to Cite

1.
Shaikh S, Ansari S, Memon FR, Malik F, Memon U, Memon AG. PROTECTIVE ROLE OF EMPAGLIFLOZIN AGAINST METHOTREXATE-INDUCED LIVER INJURY. Pak J Phsyiol [Internet]. 2026 Mar. 31 [cited 2026 Apr. 1];22(1):12-5. Available from: https://www.pjp.pps.org.pk/index.php/PJP/article/view/1886

Issue

Vol. 22 No. 1 (2026): Pakistan Journal of Physiology

Section

Original Article

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Copyright (c) 2026 Salahuddin Shaikh, Sheraz Ansari, Farzana Rahim Memon, Farheen Malik, Unshall Memon, Anjuman Gul Memon

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