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.
Highlights
The incidence of chronic kidney diseases (CKD) is increasing worldwide
The current treatment for CKD is limited to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, but emerging clinical and experimental evidence indicates that histone deacetylase inhibitors (HDACis) might be candidate therapeutic drugs for CKD
In this study, we sought to investigate whether CG200745 ((E)-2-(naphthalene-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethyl amino-propyl)-amide] 8-hydroxyamide with 1/2(L-tartaric acid)), a recently developed pan-HDACi, has renoprotective effects in the DSH rat model of kidney injury
Summary
The incidence of chronic kidney diseases (CKD) is increasing worldwide. therapies capable of curing or inhibiting disease progression are urgently needed. The current treatment for CKD is limited to angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, but emerging clinical and experimental evidence indicates that histone deacetylase inhibitors (HDACis) might be candidate therapeutic drugs for CKD. These drugs exhibit anti-fibrotic, anti-inflammatory, anti-hypertrophic, and anti-hypertensive effects [2,3]. Epigenetic modifications, such as DNA methylation or histone acetylation, are regarded as important steps in the development and progression of acute kidney injury to CKD. In this study, we sought to investigate whether CG200745 ((E)-2-(naphthalene-1-yloxymethyl)-oct-2-enedioic acid 1-[(3-dimethyl amino-propyl)-amide] 8-hydroxyamide with 1/2(L-tartaric acid)), a recently developed pan-HDACi, has renoprotective effects in the DSH rat model of kidney injury
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
