Hydrogen-rich water alleviates cyclosporine A-induced nephrotoxicity via the Keap1/Nrf2 signaling pathway

Autor: Jin Jun Liu, Chun Fang Li, Abdoulaye Issotina Zibrila, Shi Hui Yuan, Yu Yao Sun, Gong Xiao Zhao, Lynn Soong, Yi Lu, Na Na Ping, Zheng Wang
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
medicine.medical_specialty
NF-E2-Related Factor 2
Health
Toxicology and Mutagenesis
Apoptosis
Toxicology
medicine.disease_cause
Protective Agents
Biochemistry
Nephrotoxicity
Blood Urea Nitrogen
Superoxide dismutase
Rats
Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Animals
Renal Insufficiency
Molecular Biology
chemistry.chemical_classification
Reactive oxygen species
Kidney
Kelch-Like ECH-Associated Protein 1
030102 biochemistry & molecular biology
biology
Superoxide Dismutase
Water
General Medicine
Glutathione
KEAP1
Rats
Heme oxygenase
Oxidative Stress
medicine.anatomical_structure
Endocrinology
chemistry
030220 oncology & carcinogenesis
Creatinine
biology.protein
Cyclosporine
Molecular Medicine
Reactive Oxygen Species
Oxidative stress
Immunosuppressive Agents
Hydrogen
Signal Transduction
Zdroj: Journal of biochemical and molecular toxicologyREFERENCES. 34(5)
ISSN: 1099-0461
Popis: Oxidative stress induced by long-term cyclosporine A (CsA) administration is a major cause of chronic nephrotoxicity, which is characterized by tubular atrophy, tubular cell apoptosis, and interstitial fibrosis in the progression of organ transplantation. Although hydrogen-rich water (HRW) has been used to prevent various oxidative stress-related diseases, its underlying mechanisms remain unclear. This study investigated the effects of HRW on CsA-induced nephrotoxicity and its potential mechanisms. After administration of CsA (25 mg/kg/day), rats were treated with or without HRW (12 mL/kg) for 4 weeks. Renal function and vascular activity were investigated. Histological changes in kidney tissues were analyzed using Masson's trichrome and terminal deoxynucleotidyl transferase dUTP nick-end labeling stains. Oxidative stress markers and the activation of the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway were also measured. We found that CsA increased the levels of reactive oxygen species (ROS) and malonaldehyde (MDA), but it reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Such alterations induced vascular dysfunction, tubular atrophy, interstitial fibrosis, and tubular apoptosis. This was evident secondary to an increase in urinary protein, serum creatinine, and blood urea nitrogen, ultimately leading to renal dysfunction. Conversely, HRW decreased levels of ROS and MDA while increasing the activity of GSH and SOD. This was accompanied by an improvement in vascular and renal function. Moreover, HRW significantly decreased the level of Keap1 and increased the expression of Nrf2, NADPH dehydrogenase quinone 1, and heme oxygenase 1. In conclusion, HRW restored the balance of redox status, suppressed oxidative stress damage, and improved kidney function induced by CsA via activation of the Keap1/Nrf2 signaling pathway.
Databáze: OpenAIRE
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