Empagliflozin: Potential Protective Effects on Hepatocytes and Liver Outcomes in Streptozotocin -Diabetic Rats.
Alia Khwaldeh1*, Nour Al-Sawalha2, Shefa' Aljabali 1, Ziad Shraideh3, Sokiyna Ababneh1 and Roba Bdeir4

1Faculty of Allied Medical Sciences, Department of Medical Laboratory Sciences, Jadara University, Irbid, Jordan.

2Faculty of Pharmacy, Department of Clinical Pharmacy, Jordan University of Science and Technology, Irbid, Jordan

3Faculty of Science, Department of Biological Sciences, the University of Jordan, Amman, Jordan.

4Faculty of Nursing, Department of Allied Health Sciences, Al-Balqa Applied University, Al-Salt, Jordan

Corresponding Author E-mail:a.khawaldeh@jadara.edu.jo

Abstract: The current study investigated the potential positive impact of EMPA, an antidiabetic medication, on hepatocytes and liver outcomes in STZ-induced diabetic rats. Male Wistar rats were randomly assigned into four groups: control, DM (received 40mg/kg streptozotocin IP injection), DM+EMPA (received 40mg/kg streptozotocin and 10 mg/kg EMPA), and EMPA (received 10 mg/kg EMPA). Here, liver functional tests were assessed spectrophotometrically, while histological analysis of liver tissues was evaluated using light microscopy. Treated diabetic rats significantly reduced AST levels compared to treated control rats (p < 0.05). DM rats, with or without EMPA treatment, showed significantly elevated ALT levels compared to control rats (p < 0.005). Also, LDH levels were found to be lower in both treated and untreated diabetic rats compared to control rats (p < 0.0001; p < 0.05, respectively), while ALP levels were higher in both groups of diabetic rats relative to control rats (p < 0.0001; p < 0.005). Interestingly, the data showed clear trends indicating that empagliflozin-treated diabetic rats had improved liver parameters compared to untreated diabetic rats, although statistically significant differences were not observed. Remarkably, histological examination showed significant sinusoidal dilation and infiltration of inflammatory cells in hepatocytes in diabetic rats, whereas treated diabetic rats exhibited a normal hepatocyte arrangement with minor sinusoidal dilation. Altogether, the observed results suggest that EMPA may possess a protective effect on hepatocytes, thereby highlighting its potential as a therapeutic intervention for diabetes-related liver complications.

Keywords: Diabetes; EMPA; Hepatocytes, Histopathology; Liver Outcomes; STZ

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