Protective effect of D‐Cys on renal function in mice with chronic kidney disease

Abstract

MTT assay The chirality of amino acids affects their physiological functions. Recent studies uncovered potential physiological effects of D‐amino acids (D‐AAs) in nephropathy. Here, we explored the protective effects of exogenous D‐AAs on chronic kidney disease (CKD). First, by the 3‐(4,5‐dimethylthiazol‐2‐YI)‐2,5‐diphenyltetrazolium bromide (MTT) assay it was found that among the four D‐AAs studied (D‐glutamate (D‐Glu), D‐aspartic acid (D‐Asp) being the highest content in fermented yogurt, and D‐alanine (D‐Ala), D‐cysteine (D‐Cys), amino acids with renal protective potential), D‐Cys most significantly enhanced the viability of hypoxia‐induced injured HK‐2 cells, even better than its L‐analog, L‐Cys. Mitochondrial function analyzed by JC‐1 assay showed that 10 and 100 mM D‐Cys can significantly reduce the green/red fluorescence intensity by 16.1% (p < .001) and 17.6% (p < .001), respectively, in injured HK‐2 cells. Next, the in vivo protective effect of D‐Cys on adenine‐induced CKD mice was studied. The results indicated that the administration of D‐Cys decreased the serum creatinine and urea nitrogen levels by at least 15.5% and 11.8%, respectively, and significantly protected renal function in the CKD mice. Further analysis found that the administration of D‐Cys induced increased water intake in CKD mice, which is beneficial for the clearance of 2,8‐dihydroxyadenine, thereby attenuating the destruction of renal tissue structure. Moreover, H2S produced from D‐Cys resisted oxidative stress and inhibited inflammation, thus slowing down the process of renal fibrosis. In summary, this study verified the protective effect of D‐Cys on renal function and tissue structure in CKD mice, and propounded a new field of application for the utilization of D‐AAs.