Work

The direct inhibitory effects of an antioxidant, N-acetylcysteine, against calcium oxalate crystal growth, aggregation and adhesion to MDCK renal cells

Year: 2025

Type: article

Abstract: N-acetylcysteine (NAC), a potent antioxidant, can reduce nephrolithiatic pathogenesis by diminishing oxidative assault during crystalluria. However, its direct effects on calcium oxalate (CaOx) crystals that affect stone development were unknown. Herein, we examined the direct effects of NAC (at 1, 10 or 100 μM) on CaOx crystal formation, growth, aggregation, adhesion to MDCK renal cells, and internalization into the cells. The findings demonstrated that NAC at all these concentrations did not significantly affect size, number and mass of the newly generated CaOx crystals and their internalization into renal cells. However, NAC dose-dependently inhibited CaOx self-aggregation. Additionally, NAC at all concentrations significantly decreased the enlargement (growth) of the already-formed CaOx crystals and their adhesion to renal cells. Its dose-dependent inhibitory effects on crystal growth and adhesion were demonstrated at lower concentrations (0.01 and 0.1 μM). Measurement of adsorption energy (E adsorption ) between NAC molecule and Ca 2+ ion revealed adsorption or affinity between NAC and Ca 2+ . Their affinity/binding was also confirmed by an ion-selective electrode (ISE)-based titration assay. These data have shown, for the first time, the direct inhibitory effects of NAC against CaOx crystal growth, aggregation and crystal adhesion to renal cells via Ca 2+ binding that may impact the prevention of nephrolithiasis. • N-acetylcysteine (NAC) directly inhibited calcium oxalate (CaOx) crystal growth. • NAC directly inhibited CaOx crystal aggregation. • NAC directly inhibited CaOx crystal adhesion to renal cells. • Calcium-binding was the mechanism underlying inhibitory effects of NAC. • However, NAC did not affect CaOx crystallization and internalization into the cells.

Source: Food and Chemical Toxicology

DOI: 10.1016/j.fct.2025.115403

Authors: Paleerath Peerapen, Piyaporn Rattananinsruang, Pattaranit Putpeerawit, Wanida Boonmark, Visith Thongboonkerd

Institutions: Siriraj Hospital, Mahidol University

Language: English

Topic: Kidney Stones and Urolithiasis Treatments

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,670