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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1506398
This article is part of the Research Topic Cellular and Molecular Mechanisms in Metabolic Disorders: Role of Inflammation and Oxidative Stress View all 6 articles

Diphenyl diselenide protects against diabetic kidney disease through modulating gut microbiota dysbiosis in streptozotocin-induced diabetic rats

Provisionally accepted
Xing Wang Xing Wang 1*Dongmei Long Dongmei Long 2Jiaxuan Li Jiaxuan Li 1Maoting Zhou Maoting Zhou 1Xianghong Hu Xianghong Hu 1Yu Wang Yu Wang 1
  • 1 North Sichuan Medical College, Nanchong, China
  • 2 Nanchong Vocational and Technical College, Sichuan, China

The final, formatted version of the article will be published soon.

    Diphenyl diselenide (DPDS) ameliorates nephropathy in streptozotocin (STZ)-induced type 1 diabetic rats by inhibiting oxidative stress and inflammatory reactions. However, it has not been clarified whether DPDS alleviates type 1 diabetic kidney disease (DKD) is related to the inhibition of extracellular matrix (ECM) production and the regulation of intestinal flora disorder. Here, the present study investigated the effects of DPDS on ECM generation in the kidney and intestinal microflora composition in feces. The rats were orally administered DPDS or metformin for eight weeks. As a result, DPDS and metformin improved the DKD in STZ rats, as evidenced by decreased blood glucose, BUN, urine volume, urine microalbumin, urinary β2 microglobulin, and improvement of renal pathological morphology. Furthermore, DPDS intervention markedly reduced the protein expression of α-SMA, COI Ⅳ, FN, and vimentin in the kidneys. Besides, DPDS not only improved dyslipidemia in STZ diabetic rats, but also enhanced the activities of antioxidant enzymes, decreased the level of MDA in serum and kidney, and regulated the expression of proteins related to the Nrf2/Keap1 signaling pathway in the kidney. Moreover, we found that DPDS could selectively improve the relative abundance of probiotics as well as the diversity of flora, thus ameliorating the intestinal microbial composition of the STZ rats, significantly regulating the intestinal microbial homeostasis. Overall, DPDS inhibited ECM production and improved renal pathological changes, which may be related to reducing oxidative stress damage in the kidney and improving intestinal flora imbalance, providing data support for the further development and application of DPDS in DKD.

    Keywords: Diphenyl diselenide, diabetic nephropathy, Extracellular Matrix, Oxidative Stress, Nrf2/Keap1 signaling, Gut Microbiota

    Received: 05 Oct 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 Wang, Long, Li, Zhou, Hu and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xing Wang, North Sichuan Medical College, Nanchong, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.