Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2025; 16(1): 92711
Published online Jan 15, 2025. doi: 10.4239/wjd.v16.i1.92711
Mizagliflozin ameliorates diabetes induced kidney injury by inhibitor inhibit inflammation and oxidative stress
Zhi-Min Lin, Han-Yuan Gao, Shu-Han Shi, Yue-Ting Li
Zhi-Min Lin, Han-Yuan Gao, Shu-Han Shi, Yue-Ting Li, Department of Nephrology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China
Author contributions: Lin ZM, Gao HY, Shi SH, and Li YT participated in the conceptualization; Gao HY, Shi SH, and Li YT contributed to the data curation, formal analysis, funding acquisition, investigation, and methodology of this manuscript; Shi SH and Li YT were involved in the project administration, resources, software, supervision, validation, visualization, writing - original draft, and writing - review & editing of this study. All authors have read and approve the final manuscript.
Institutional review board statement: Our study received approval from the ethics committee of the Second Affiliated Hospital of Fujian Medical University, No. FJSS20111511.
Institutional animal care and use committee statement: Our study received approval from the Institutional Animal Care and Use Committee, No. FJSS20111511.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data used to support the findings of this study are included within the article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yue-Ting Li, MM, Chief Physician, Associate Professor, Department of Nephrology, The Second Affiliated Hospital of Fujian Medical University, No. 34 Zhongshan North Road, Licheng District, Quanzhou 362000, Fujian Province, China. yuetingli20230125@163.com
Received: February 5, 2024
Revised: April 26, 2024
Accepted: October 8, 2024
Published online: January 15, 2025
Processing time: 298 Days and 18.4 Hours
Abstract
BACKGROUND

Mizagliflozin (MIZ) is a specific inhibitor of sodium-glucose cotransport protein 1 (SGLT1) originally developed as a medication for diabetes.

AIM

To explore the impact of MIZ on diabetic nephropathy (DN).

METHODS

Diabetic mice were created using db/db mice. They were administered either a low dose (0.5 mg/kg) or a high dose (1.0 mg/kg) of the SGLT1 inhibitor MIZ via stomach gavage for 8 weeks. Subsequently, mesangial cells (MCs) were isolated and subjected to high glucose conditions in culture to assess the effects of MIZ on DN.

RESULTS

The results showed that low doses of MIZ significantly reduced albuminuria to a level comparable to that achieved with high doses in db/db mice. High doses of MIZ led to a substantial increase in body weight in mice, along with decreased blood glucose levels and food intake. Moreover, the intervention with high-dose MIZ notably decreased the expression of extracellular matrix genes, such as collagen type 1 alpha 1 mRNA levels. While the expression of SGLT1 increased after exposure to high glucose, it decreased following treatment with MIZ. Furthermore, MIZ intervention was more effective in improving lactate dehydrogenase levels in MCs induced by high glucose compared to canagliflozin. MIZ also significantly elevated levels of antioxidant enzymes superoxide dismutase, catalase, and glutathione, while reducing malondialdehyde levels.

CONCLUSION

These findings indicate that MIZ can ameliorate DN by inhibiting SGLT1, inflammation, and oxidative stress.

Keywords: Mizagliflozin; Sodium-glucose cotransport protein 1; Diabetic nephropathy; Mesangial cells

Core Tip: Diabetic nephropathy is a common and serious complication of diabetes, characterized by the accumulation of extracellular matrix in the renal units. Mizagliflozin can improve diabetic nephropathy impairment by inhibiting neural sodium-glucose cotransport protein 1, inflammation, and oxidative stress. Its functions are regarded as positive regulators of inflammation and oxidative stress. These findings offer new treatment methods targeting sodium-glucose cotransport protein 1 inhibitors for diabetic kidney disease.