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Int J Mol Sci. 2019 Jan 25;20(3). pii: E508. doi: 10.3390/ijms20030508.

Renoprotective Effect of the Histone Deacetylase Inhibitor CG200745 in DOCA-Salt Hypertensive Rats.

Author information

1
Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea. baedak7@gmail.com.
2
Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea. remon9127@hanmail.net.
3
Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea. xlzlzl1103@gmail.com.
4
Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea. hongsang38@hanmail.net.
5
Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea. laminion@hanmail.net.
6
Department of Pharmacology, Chonnam National University Medical School, Hwasun 58128, Korea. eomgh@jnu.ac.kr.
7
Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 41944, Korea. inkim@knu.ac.kr.
8
CrystalGenomics, Inc., 5F, Bldg A, Korea Bio Park, Seongnam 13488, Korea. hjcha@cgxinc.com.
9
CrystalGenomics, Inc., 5F, Bldg A, Korea Bio Park, Seongnam 13488, Korea. jmcho@cgxinc.com.
10
Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea. drmsk@hanmail.net.
11
Department of Internal Medicine, Chonnam National University Medical School, Gwangju 61469, Korea. skimw@chonnam.ac.kr.

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.

KEYWORDS:

CG200745; DOCA; HDAC inhibitor; fibrosis; hypertension; inflammation

PMID:
30691015
PMCID:
PMC6387176
DOI:
10.3390/ijms20030508
[Indexed for MEDLINE]
Free PMC Article

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