Canagliflozin‐induced renal glutathione distribution mapping in non‐diabetic male rat kidneys
Abstract 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...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2025-04-01
|
| Series: | Physiological Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.14814/phy2.70320 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849724779271028736 |
|---|---|
| author | Guy Watanabe Shoichiro Horita Reika Flora Moriya Yusuke Masuishi Shingen Misaka Shu Taira Kenju Shimomura Michio Shimabukuro Junichiro James Kazama |
| author_facet | Guy Watanabe Shoichiro Horita Reika Flora Moriya Yusuke Masuishi Shingen Misaka Shu Taira Kenju Shimomura Michio Shimabukuro Junichiro James Kazama |
| author_sort | Guy Watanabe |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-5a23dfa2e599437d8b5f5ce44100da7d |
| institution | DOAJ |
| issn | 2051-817X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj-art-5a23dfa2e599437d8b5f5ce44100da7d2025-08-20T03:10:39ZengWileyPhysiological Reports2051-817X2025-04-01137n/an/a10.14814/phy2.70320Canagliflozin‐induced renal glutathione distribution mapping in non‐diabetic male rat kidneysGuy Watanabe0Shoichiro Horita1Reika Flora Moriya2Yusuke Masuishi3Shingen Misaka4Shu Taira5Kenju Shimomura6Michio Shimabukuro7Junichiro James Kazama8Department of Nephrology and Hypertension Fukushima Medical University School of Medicine Fukushima JapanDepartment of Diabetes, Endocrinology, and Metabolism Fukushima Medical University School of Medicine Fukushima JapanDepartment of Nephrology and Hypertension Fukushima Medical University School of Medicine Fukushima JapanDepartment of Hygiene and Preventive Medicine Fukushima Medical University School of Medicine Fukushima JapanDepartment of Bioregulation and Pharmacological Medicine Fukushima Medical University School of Medicine Fukushima JapanFaculty of Food and Agricultural Sciences Fukushima University Fukushima JapanDepartment of Bioregulation and Pharmacological Medicine Fukushima Medical University School of Medicine Fukushima JapanDepartment of Diabetes, Endocrinology, and Metabolism Fukushima Medical University School of Medicine Fukushima JapanDepartment of Nephrology and Hypertension Fukushima Medical University School of Medicine Fukushima JapanAbstract 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.https://doi.org/10.14814/phy2.70320canagliflozinglutathionemass spectroscopy imagingoxidative stressSGLT2 inhibitor |
| spellingShingle | Guy Watanabe Shoichiro Horita Reika Flora Moriya Yusuke Masuishi Shingen Misaka Shu Taira Kenju Shimomura Michio Shimabukuro Junichiro James Kazama Canagliflozin‐induced renal glutathione distribution mapping in non‐diabetic male rat kidneys Physiological Reports canagliflozin glutathione mass spectroscopy imaging oxidative stress SGLT2 inhibitor |
| title | Canagliflozin‐induced renal glutathione distribution mapping in non‐diabetic male rat kidneys |
| title_full | Canagliflozin‐induced renal glutathione distribution mapping in non‐diabetic male rat kidneys |
| title_fullStr | Canagliflozin‐induced renal glutathione distribution mapping in non‐diabetic male rat kidneys |
| title_full_unstemmed | Canagliflozin‐induced renal glutathione distribution mapping in non‐diabetic male rat kidneys |
| title_short | Canagliflozin‐induced renal glutathione distribution mapping in non‐diabetic male rat kidneys |
| title_sort | canagliflozin induced renal glutathione distribution mapping in non diabetic male rat kidneys |
| topic | canagliflozin glutathione mass spectroscopy imaging oxidative stress SGLT2 inhibitor |
| url | https://doi.org/10.14814/phy2.70320 |
| work_keys_str_mv | AT guywatanabe canagliflozininducedrenalglutathionedistributionmappinginnondiabeticmaleratkidneys AT shoichirohorita canagliflozininducedrenalglutathionedistributionmappinginnondiabeticmaleratkidneys AT reikafloramoriya canagliflozininducedrenalglutathionedistributionmappinginnondiabeticmaleratkidneys AT yusukemasuishi canagliflozininducedrenalglutathionedistributionmappinginnondiabeticmaleratkidneys AT shingenmisaka canagliflozininducedrenalglutathionedistributionmappinginnondiabeticmaleratkidneys AT shutaira canagliflozininducedrenalglutathionedistributionmappinginnondiabeticmaleratkidneys AT kenjushimomura canagliflozininducedrenalglutathionedistributionmappinginnondiabeticmaleratkidneys AT michioshimabukuro canagliflozininducedrenalglutathionedistributionmappinginnondiabeticmaleratkidneys AT junichirojameskazama canagliflozininducedrenalglutathionedistributionmappinginnondiabeticmaleratkidneys |