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Role of mitochondrial dysfunction in renal fibrosis promoted by hypochlorite-modified albumin in a remnant kidney model and protective effects of antioxidant peptide SS-31
- Source :
- European journal of pharmacology. 804
- Publication Year :
- 2017
-
Abstract
- Oxidative stress aggravates renal fibrosis, a pathway involved in almost all forms of chronic kidney disease (CKD). However, the underlying mechanism involved in the pathogenesis of renal oxidative stress has not been completely elucidated. In this study, we explored the role and mechanism of hypochlorite-modified albumin (HOCl-alb) in mediating oxidative stress and fibrotic response in a remnant-kidney rat model. Five-sixths nephrectomy (5/6 NX) was performed on the rats and then the animals were randomly assigned to intravenous treatment with either vehicle alone, or HOCl-rat serum albumin (RSA) in the presence or absence of SS-31 (administered intraperitoneally). A sham-operation control group was set up concurrently. Compared with the control group, 5/6 NX animals displayed marked mitochondrial (mt) dysfunction, as evidenced by decrease of mitochondrial membrane potential (MMP), ATP production, mtDNA copy number alterations and manganese superoxide dismutase (MnSOD) activity, release of cytochrome C (Cyto C) from mitochondria to the cytoplasm, and increase of mitochondrial reactive oxygen species in renal tissues. They also displayed increased levels of HOCl-alb in both plasma and renal tissues. These changes were accompanied by accumulation of extracellular matrix, worsened proteinuria, deteriorated renal function, and a marked increase of macrophage infiltration along with up-regulation of monocyte chemoattractant protein (MCP)-1 and transforming growth factor (TGF)-β1 expression. HOCl-alb challenge further exacerbated the above biological effects in 5/6 NX animals, but these adverse effects were prevented by administration of SS-31, a mitochondrial targeted antioxidant peptide. These data suggest that accumulation of HOCl-alb may promote renal inflammation and fibrosis, probably related to mitochondrial oxidative stress and dysfunction and that the mitochondrial targeted peptide SS-31 might be a novel therapy for renal fibrosis and chronic renal failure (CRF).
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Serum albumin
Renal function
Mitochondrion
medicine.disease_cause
Kidney
Antioxidants
Rats, Sprague-Dawley
03 medical and health sciences
Fibrosis
Internal medicine
Renal fibrosis
medicine
Animals
Serum Albumin
Pharmacology
chemistry.chemical_classification
Reactive oxygen species
biology
Chemistry
medicine.disease
Extracellular Matrix
Hypochlorous Acid
Mitochondria
Up-Regulation
Oxidative Stress
030104 developmental biology
Endocrinology
Biochemistry
Cytoprotection
biology.protein
Oligopeptides
Oxidative stress
Biomarkers
Kidney disease
Subjects
Details
- ISSN :
- 18790712
- Volume :
- 804
- Database :
- OpenAIRE
- Journal :
- European journal of pharmacology
- Accession number :
- edsair.doi.dedup.....9fcf187dd76ba5df8f9f5bcd920dcd99