# Investigating the Role of Empagliflozin in the Pathological Progress of Ischemia-Reperfusion Injury in Rat Kidneys: The Involvement of Nitric Oxide

## TL;DR

This study shows that empagliflozin protects rat kidneys from ischemia-reperfusion injury, likely by boosting nitric oxide levels.

## Contribution

The study demonstrates empagliflozin's protective role in kidney I/R injury via the nitric oxide pathway in rats.

## Key findings

- Empagliflozin reduced creatinine, urea, inflammation, and oxidative stress in rats.
- Histopathology showed empagliflozin mitigated kidney damage from ischemia-reperfusion.
- L-arginine enhanced empagliflozin's effects, while L-NAME reduced its benefits.

## Abstract

Renal ischemia-reperfusion (RIR) is a pathological condition that can lead to severe outcomes due to damage to kidney structures. Additionally, oxidative stress is triggered by mitochondrial disruption during reperfusion, potentially resulting in necrosis and, ultimately, cell death through the destruction of cellular membranes.

Thirty rats were included in this study and divided into the following groups: healthy rats, an ischemia-reperfusion (I/R) group, an I/R group treated with empagliflozin, an I/R group treated with empagliflozin plus L-NAME, and an I/R group treated with empagliflozin plus L-arginine. The drugs were administered from three days before I/R induction to one day post-operation. Blood samples were collected 24 hours after I/R induction to evaluate renal function, inflammatory markers, and oxidative stress. Subsequently, the right kidney was harvested for nitric oxide (NO) measurement, while the left kidney was used for histological analysis.

Empagliflozin administration significantly reduced creatinine, urea, inflammatory markers, and oxidative stress levels. Moreover, empagliflozin increased the levels of antioxidant enzymes and NO. Histopathological analysis indicated that empagliflozin mitigated ischemia-reperfusion injury in renal tissue. The protective effects were further enhanced with the co-administration of empagliflozin and L-arginine. In contrast, simultaneous treatment with empagliflozin and L-NAME led to pathological changes associated with ischemia-reperfusion and attenuated the beneficial effects of empagliflozin.

The findings of this study suggest that empagliflozin exerts protective effects against ischemia-reperfusion injury, likely through the NO pathway.