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Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress

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Abstract

This study aims to elucidate the mechanism and potential of Rhizoma alismatis polysaccharides (RAPs) in preventing oxidative damage to human renal proximal tubule epithelial cells. The experimental approach involved incubating HK-2 cells with 100 nm calcium oxalate monohydrate for 24 h to establish a cellular injury model. Protection was provided by RAPs with varying carboxyl group contents: 3.57%, 7.79%, 10.84%, and 15.33%. The safeguarding effect of RAPs was evaluated by analyzing relevant cellular biochemical indicators. Findings demonstrate that RAPs exhibit notable antioxidative properties. They effectively diminish the release of reactive oxygen species, lactate dehydrogenase, and malondialdehyde, a lipid oxidation byproduct. Moreover, RAPs enhance superoxide dismutase activity and mitochondrial membrane potential while attenuating the permeability of the mitochondrial permeability transition pore. Additionally, RAPs significantly reduce levels of inflammatory factors, including NLRP3, TNF-α, IL-6, and NO. This reduction corresponds to the inhibition of overproduced pro-inflammatory mediator nitric oxide and the caspase 3 enzyme, leading to a reduction in cellular apoptosis. RAPs also display the ability to suppress the expression of the HK-2 cell surface adhesion molecule CD44. The observed results collectively underscore the substantial anti-inflammatory and anti-apoptotic potential of all four RAPs. Moreover, their capacity to modulate the expression of cell surface adhesion molecules highlights their potential in inhibiting the formation of kidney stones. Notably, RAP3, boasting the highest carboxyl group content, emerges as the most potent agent in this regard.

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Data availability

The authors confirm that the data supporting the findings of this study are available within the article.

Abbreviations

RAPs:

Rhizoma alismatis polysaccharides

CaOx:

Calcium oxalate

COM:

CaOx monohydrate

COD:

CaOx dihydrate

mPTP:

The mitochondrial permeability transition pore

ROS:

Reactive oxygen species

MCP-1:

Monocyte chemokine-1

OPN:

Osteopontin

TNF-α:

Tumor necrosis factor alpha

IL-6:

Interleukin-6

LPS:

Lipopolysaccharide

MCP:

Momordica charantia polysaccharides

NO:

Nitric oxide

IL-1β:

Interleukin-1β

iNOS:

Inducible NO synthase

COX-2:

Cyclooxygenase-2

FBS :

Fetal bovine serum

LDH :

Lactate dehydrogenase

SOD:

Superoxide dismutase

MDA:

Malondialdehyde

ΔΨm:

Mitochondrial membrane potential

AO/EB:

Acridine orange/ethidium bromide

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Funding

This work was supported by the National Natural Science Foundation of China (No. 82270800), Clinical Research Center For Pediatric Genitourinary Disease In Hunan Province (No. 2021SK4017) and the Scientific Research Project of Hunan Provincial Health Commission (No. 202204054938).

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Authors and Affiliations

  1. Department of urology, The Affiliated Children’s Hospital of Xiangya School of Medicine, Central South University (Hunan Children’s Hospital), Changsha, 410007, China

    Zhi Wang, Li Liu, Chuang-Ye Li & Yao-Wang Zhao

  2. Institute of Biomineralization and Lithiasis Research, College of Chemistry and Materials Science, Jinan University, Guangzhou, 510632, China

    Xin-Yi Tong, Xiao-Yan Cheng & Jian-Ming Ouyang

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  1. Zhi Wang
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  2. Li Liu
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Zhi Wang, Li Liu, Chuang-Ye Li, Xin-Yi Tong, and Xiao-Yan Cheng wrote the main manuscript text; Yao-Wang Zhao* and Jian-Ming Ouyang* are directors.

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Correspondence to Yao-Wang Zhao or Jian-Ming Ouyang.

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Wang, Z., Liu, L., Li, CY. et al. Carboxymethylated Rhizoma alismatis polysaccharides reduces the risk of calcium oxalate stone formation by reducing cellular inflammation and oxidative stress. Urolithiasis 52, 63 (2024). https://doi.org/10.1007/s00240-024-01565-4

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