N-acetylcysteine Ameliorates Vancomycin-induced Nephrotoxicity by Inhibiting Oxidative Stress and Apoptosis in the<i> in vivo</i> and <i>in vitro</i> Models

Yu, Ping; Luo, Jing; Song, Huahua; Qian, Tianwei; He, Xuan; Fang, Jie; Dong, Wenpei; Bian, Xiaolan

doi:10.7150/ijms.69807

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Int J Med Sci 2022; 19(4):740-752. doi:10.7150/ijms.69807 This issue Cite

Research Paper

N-acetylcysteine Ameliorates Vancomycin-induced Nephrotoxicity by Inhibiting Oxidative Stress and Apoptosis in the in vivo and in vitro Models

Ping Yu^1,2#, Jing Luo^3#, Huahua Song³, Tianwei Qian³, Xuan He¹, Jie Fang¹, Wenpei Dong^2✉, Xiaolan Bian^1✉

1. Department of Pharmacy, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
2. Department of General Surgery, Huadong Hospital, Fudan University, Shanghai, China.
3. Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
# Ping Yu and Jing Luo contributed equally to the study.

Citation:

Yu P, Luo J, Song H, Qian T, He X, Fang J, Dong W, Bian X. N-acetylcysteine Ameliorates Vancomycin-induced Nephrotoxicity by Inhibiting Oxidative Stress and Apoptosis in the in vivo and in vitro Models. Int J Med Sci 2022; 19(4):740-752. doi:10.7150/ijms.69807. https://www.medsci.org/v19p0740.htm

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Abstract

Background: Oxidative stress-related apoptosis is considered as the key mechanism implicated in the pathophysiology of nephrotoxicity with vancomycin (VCM) therapy. We evaluated the possible effects of N-acetylcysteine (NAC) on VCM-induced nephrotoxicity and the underlying mechanism.

Methods: VCM-induced nephrotoxicity was established using HK-2 cells and SD rats and observed by measuring cell survival, kidney histological changes, renal function and kidney injury related markers (KIM-1 and NGAL). Oxidative stress, renal cell apoptosis and the involved signaling pathways were also evaluated.

Results: In model rats, NAC could protect against VCM-induced acute kidney injury with histological damage, renal dysfunction, and increased Cre and BUN levels. In HK-2 cells, VCM-induced decreased cell viability was restored by NAC. In addition, increased expression of caspase-3, KIM-1 and NGAL suffering from VCM was also reversed by NAC in vivo and in vitro. NAC inhibited ROS production, decreased cell apoptosis by decreasing the Bax/Bcl-2 ratio and caspase-3 expression in HK-2 cells and regulated oxidative stress indicators in the kidney by decreasing GSH, SOD and CAT activity and increasing MDA levels. Furthermore, NAC could effectively reverse VCM-associated increased P38 MAPK/JNK phosphorylation.

Conclusions: The results demonstrated that NAC had a protective effect against nephrotoxicity from VCM by inhibiting oxidative stress and apoptosis via P38 MAPK/JNK.

Keywords: vancomycin, nephrotoxicity, N-acetylcysteine, oxidative stress, renal protection

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APA

Yu, P., Luo, J., Song, H., Qian, T., He, X., Fang, J., Dong, W., Bian, X. (2022). N-acetylcysteine Ameliorates Vancomycin-induced Nephrotoxicity by Inhibiting Oxidative Stress and Apoptosis in the in vivo and in vitro Models. International Journal of Medical Sciences, 19(4), 740-752. https://doi.org/10.7150/ijms.69807.

ACS

Yu, P.; Luo, J.; Song, H.; Qian, T.; He, X.; Fang, J.; Dong, W.; Bian, X. N-acetylcysteine Ameliorates Vancomycin-induced Nephrotoxicity by Inhibiting Oxidative Stress and Apoptosis in the in vivo and in vitro Models. Int. J. Med. Sci. 2022, 19 (4), 740-752. DOI: 10.7150/ijms.69807.

NLM

CSE

Yu P, Luo J, Song H, Qian T, He X, Fang J, Dong W, Bian X. 2022. N-acetylcysteine Ameliorates Vancomycin-induced Nephrotoxicity by Inhibiting Oxidative Stress and Apoptosis in the in vivo and in vitro Models. Int J Med Sci. 19(4):740-752.

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