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Renoprotective Effect of the Histone Deacetylase Inhibitor CG200745 in DOCA-Salt Hypertensive Rats.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2019 Jan 25; Vol. 20 (3). Date of Electronic Publication: 2019 Jan 25. - Publication Year :
- 2019
-
Abstract
- The novel histone deacetylase inhibitor CG200745 was initially developed to treat various hematological and solid cancers. We investigated the molecular mechanisms associated with the renoprotective effects of CG200745 using deoxycorticosterone acetate (DOCA)-salt hypertensive (DSH) rats. DOCA strips (200 mg/kg) were implanted into rats one week after unilateral nephrectomy. Two weeks after DOCA implantation, DSH rats were randomly divided into two groups that received either physiological saline or CG200745 (5 mg/kg/day) for another two weeks. The extent of glomerulosclerosis and tubulointerstitial fibrosis was determined by Masson's trichrome staining. The renal expression of fibrosis and inflammatory markers was detected by semiquantitative immunoblotting, a polymerase chain reaction, and immunohistochemistry. Pathological signs such as glomerulosclerosis, tubulointerstitial fibrosis, increased systolic blood pressure, decreased creatinine clearance, and increased albumin-to-creatinine ratios in DSH rats were alleviated by CG200745 treatment compared to those manifestations in positive control animals. Furthermore, this treatment counteracted the increased expression of αSMA, TGF-β1, and Bax, and the decreased expression of Bcl-2 in the kidneys of DSH rats. It also attenuated the increase in the number of apoptotic cells in DSH rats. Thus, CG200745 can effectively prevent the progression of renal injury in DSH rats by exerting anti-inflammatory, anti-fibrotic, and anti-apoptotic effects.
- Subjects :
- Actins metabolism
Albumins metabolism
Animals
Apoptosis drug effects
Biomarkers metabolism
Creatinine metabolism
Disease Models, Animal
Histone Deacetylase Inhibitors pharmacology
Hydroxamic Acids pharmacology
Hypertension chemically induced
Hypertension complications
Kidney Diseases metabolism
Male
Naphthalenes pharmacology
Random Allocation
Rats
Rats, Sprague-Dawley
Transforming Growth Factor beta1 metabolism
Desoxycorticosterone Acetate adverse effects
Histone Deacetylase Inhibitors administration & dosage
Hydroxamic Acids administration & dosage
Hypertension drug therapy
Kidney Diseases prevention & control
Naphthalenes administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 20
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 30691015
- Full Text :
- https://doi.org/10.3390/ijms20030508