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s-Ethyl cysteine, an amino acid derivative, attenuated cisplatin induced nephrotoxicity

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Abstract

Renal protection from s-ethyl cysteine (SEC) against cisplatin (CP)-induced inflammatory and oxidative injury was examined. Mice were divided into five groups: normal group, 0.25% SEC group, CP group, 0.125% SEC + CP group, 0.25% SEC + CP group. After 2 weeks supplementation, mice of CP and SEC + CP groups received CP treatment. H&E stain showed that CP caused infiltration of inflammatory cells and necrosis of tubular cells. SEC pre-treatments attenuated CP-induced inflammatory injury and degeneration. SEC pre-treatments limited CP-stimulated release of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and prostaglandin E2 in kidney. CP raised the renal activity and mRNA expression of cyclooxygenase-2 and nuclear factor kappa B. SEC pre-treatments reversed these alterations. CP increased the production of reactive oxygen species and nitric oxide, and lowered glutathione content, glutathione peroxidase and glutathione reductase activities in kidney. SEC pre-treatments reversed these changes. CP up-regulated renal inducible nitric oxide synthase (iNOS) mRNA expression, and down-regulated nuclear factor E2-related factor (Nrf)-2 and heme oxygenase (HO)-1 mRNA expression. SEC pre-treatments suppressed iNOS mRNA expression; and enhanced renal Nrf2 and HO-1 mRNA expression. These novel findings suggest that dietary SEC via exerting its multiple bio-functions could be considered as a protective agent for kidney against CP.

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Abbreviations

AKI:

Acute kidney injury

ALT:

Alanine transaminase

ARE:

Antioxidant-response element

AST:

Aspartate transaminase

BUN:

Blood urea nitrogen

BW:

Body weight

COX:

Cyclooxygenase

CP:

Cisplatin

Cr:

Creatinine

DCFH-DA:

Dichlorofluorescein diacetate

FI:

Feed intake

GFR:

Glomerular filtration rate

GPX:

Glutathione peroxidase

GR:

Glutathione reductase

GSH:

Glutathione

HO:

Heme oxygenase

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

NF-κB:

Nuclear factor kappa B

NO:

Nitric oxide

Nrf2:

Nuclear factor E2-related factor 2

PGE:

Prostaglandin E

ROS:

Reactive oxygen species

RT-PCR:

Real-time polymerase chain reaction

SEC:

s-Ethyl cysteine

TNF:

Tumor necrosis factor

WI:

Water intake

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Acknowledgements

All authors thank Asia University for a grant support.

Funding

This study was partially supported by a Grant from Asia University, Taichung, Taiwan (ASIA-107-CMUH-05).

Author information

Author notes

  1. Huey-Liang Kuo and Mei-Chin Mong equally contributed to this study.

Authors and Affiliations

  1. Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

    Huey-Liang Kuo

  2. Department of Food Nutrition and Health Biotechnology, Asia University, Taichung, Taiwan

    Mei-Chin Mong, Zhi-Hong Wang & Mei-Chin Yin

  3. Division of Nephrology, Asia University Hospital, Taichung, Taiwan

    Hung-Chih Chen

  4. Department of Medical Research, China Medical University Hospital, Taichung, Taiwan

    Mei-Chin Yin

Authors
  1. Huey-Liang Kuo
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  2. Mei-Chin Mong
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  3. Hung-Chih Chen
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  4. Zhi-Hong Wang
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  5. Mei-Chin Yin
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Corresponding author

Correspondence to Mei-Chin Yin.

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All authors declare that no conflict of interest.

Ethical approval

All experiments performed in animal study were approved by the Institutional Animal Care and Use Committee (IACUC) of Asia University (Taichung, Taiwan). All procedures followed the ethical standards of this institution.

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Handling Editor: G. J. Peters.

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Kuo, HL., Mong, MC., Chen, HC. et al. s-Ethyl cysteine, an amino acid derivative, attenuated cisplatin induced nephrotoxicity. Amino Acids 52, 1181–1190 (2020). https://doi.org/10.1007/s00726-020-02882-9

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  • DOI: https://doi.org/10.1007/s00726-020-02882-9

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