Utilizing methylglyoxal and D-lactate in urine to evaluate saikosaponin C treatment in mice with accelerated nephrotoxic serum nephritis

Abstract

The relationship between methylglyoxal (MGO) and D-lactate during saikosaponin C (SSC) treatment of mice with accelerated nephrotoxic serum (NTS) nephritis was investigated. NTS nephritis was induced by administration of anti-basement membrane antibodies to C57BL/6 mice and three dosages of SSC were administered for 14 days. Proteinuria, blood urea nitrogen, serum creatinine, renal histology, urinary MGO and d-lactate changes were examined. Compared to the NTS control group, the middle dosage (10 mg/kg/day) of SSC significantly alleviated the development of nephritis based on urine protein measurements (34.40 ± 6.85 vs. 17.33 ± 4.79 mg/day, p<0.05). Pathological observation of the glomerular basement membrane (GBM) revealed monocyte infiltration, hypertrophy, and crescents were alleviated, and injury scoring also showed improved efficacy for the middle dose of SSC during nephritis (7.92 ± 1.37 vs. 3.50 ± 1.14, p<0.05). Moreover, the significant decreases in urinary levels of MGO (24.71 ± 3.46 vs. 16.72 ± 2.36 μg/mg, p<0.05) and D-lactate (0.31 ± 0.04 vs. 0.23 ± 0.02 μmol/mg, p<0.05) were consistent with the biochemical and pathological examinations. This study demonstrates that MGO and D-lactate may reflect the extent of damage and the efficacy of SSC in NTS nephritis; further studies are required to enable clinical application.