1. Renoprotective Effect of the Histone Deacetylase Inhibitor CG200745 in DOCA-Salt Hypertensive Rats.
- Author
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Bae EH, Kim IJ, Song JH, Choi HS, Kim CS, Eom GH, Kim I, Cha H, Cho JM, Ma SK, and Kim SW
- 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
- 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.
- Published
- 2019
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