Canagliflozin‐induced renal glutathione distribution mapping in non‐diabetic male rat kidneys

Canagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, has direct renoprotective effects beyond lowering blood glucose levels. The inhibition of sodium reabsorption via SGLT2 reduces the overload on proximal tubules, thereby suppressing the generation of reactive oxygen species (ROS) and preventing a decline in renal function. To clarify the pharmacological mechanism of SGLT2 inhibitor, we investigated the effects of canagliflozin on oxidative stress in the kidneys of normal, non-diabetic Sprague-Dawley rats. Screening using mass spectrometry images revealed a significant elevation map of the reduced form of glutathione in the renal cortex of canagliflozin-treated non-diabetic rats. These results suggest that canagliflozin reduces oxidative stress through ROS scavenging mechanisms. Considering that ROS play major roles in renal dysfunction regardless of diabetes mellitus, these findings suggest that canagliflozin is applicable to a broader range of renal diseases beyond diabetes.