2. Academic Validation
  3. Metformin ameliorates calcium oxalate crystallization and stone formation by activating the Nrf2/HO-1 signaling pathway: Two birds with one stone

Metformin ameliorates calcium oxalate crystallization and stone formation by activating the Nrf2/HO-1 signaling pathway: Two birds with one stone

  • Arch Biochem Biophys. 2023 Mar 11;109568. doi: 10.1016/j.abb.2023.109568.
Xiaofang Zhang 1,  Futu Liang 1,  Tianyang Li 1,  Yaodong Jiang 2,  Fei Ren 3
Affiliations

Affiliations

  • 1 Department of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China.
  • 2 Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China. Electronic address: jyd@smu.edu.cn.
  • 3 Department of Pharmacy, Clinical Pharmacy Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, PR China. Electronic address: renfei@smu.edu.cn.
PMID: 36914110 DOI: 10.1016/j.abb.2023.109568
Abstract

Deposition of calcium oxalate (CaOx) crystals and oxidative stress-induced injury of renal tubular epithelial cell are the primary pathogenic factors of nephrolithiasis. In this study we investigated the beneficial effects of metformin hydrochloride (MH) against nephrolithiasis and explored the underlying molecular mechanism. Our results demonstrated that MH inhibited the formation of CaOx crystals and promoted the transformation of thermodynamically stable CaOx monohydrate (COM) to more unstable CaOx dihydrate (COD). MH treatment effectively ameliorated oxalate-induced oxidative injury and mitochondrial damage in renal tubular cells and reduced CaOx crystal deposition in rat kidneys. MH also attenuated oxidative stress by lowering MDA level and enhancing SOD activity in HK-2 and NRK-52E cells and in a rat model of nephrolithiasis. In both in HK-2 and NRK-52E cells, COM exposure significantly lowered the expressions of HO-1 and Nrf2, which was rescued by MH treatment even in the presence of Nrf2 and HO-1 inhibitors. In rats with nephrolithiasis, MH treatment significantly rescued the down-regulation of the mRNA and protein expression of Nrf2 and HO-1 in the kidneys. These results demonstrate that MH can alleviate CaOx crystal deposition and kidney tissue injury in rats with nephrolithiasis by suppressing oxidative stress and activating the Nrf2/HO-1 signaling pathway, suggesting the potential value of MH in the treatment of nephrolithiasis.

Keywords

Calcium oxalate formation; Metformin hydrochloride; Nephrolithiasis; Nrf2/HO-1; Oxidative stress.

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