title: Vorinostat protects against calcium oxalate-induced kidney injury in mice.
abstract: The present study aimed to examine the effect of the histone deacetylase inhibitor, vorinostat (SAHA), on renal function in a calcium oxalate crystal mouse model, and to investigate the mechanism underlying the renoprotective effect of SAHA. Calcium oxalate crystal formation was induced in 8 week‑old male C57BL/6 mice by administering 100 mg/kg glyoxylate for 7 days. A total of 24 male C57BL/6 mice were randomly divided into a control group and the following experimental groups: 50 mg/kg normal saline + 100 mg/kg glyoxylate; 50 mg/kg dimethyl sulfoxide (DMSO) + 100 mg/kg glyoxylate; and 50 mg/kg SAHA + 100 mg/kg glyoxylate. The mice in each of the experimental groups were injected with the saline, DMSO or SAHA into their abdominal cavities 6 h prior to the glyoxylate injection. The mice were sacrificed after 7 days, following which blood and urine samples were collected. The kidneys were harvested to analyze the levels of calcium concentrations and the levels of malondialdehyde (MDA), superoxide dismutase and glutathione reductase. Immunohistochemical staining and semi‑quantitative analyses were performed to detect the expression levels of osteopontin (OPN) and CD44. Renal tubular cell apoptosis was detected using a TUNEL assay. The concentrations of calcium and malondialdehyde were significantly decreased in the SAHA group, and calcium oxalate crystals in the kidney tissue and the expression levels of OPN and CD44 in the SAHA group were lower, compared with the other experimental groups. SAHA significantly reduced the urinary excretion of KIM‑1 and renal tubular cell apoptosis. In conclusion, SAHA reduced calcium oxalate crystal deposition and protected against kidney injury.
authors.affiliation: Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Zhongjiang
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Department of Cell Biology, Division of Basic Medicine, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Changcheng
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Caihong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Changhai Hospital, Second Military Medical University, Shanghai 200433, P.R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Guo
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis; D002129:Calcium Oxalate; D004353:Drug Evaluation, Preclinical; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D018960:Hyaluronan Receptors / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D053495:Osteopontin / Q000378:metabolism; D018384:Oxidative Stress; D000077337:Vorinostat
chemical_list: C476399:Cd44 protein, mouse; D056572:Histone Deacetylase Inhibitors; D018960:Hyaluronan Receptors; D006877:Hydroxamic Acids; C506896:Spp1 protein, mouse; D053495:Osteopontin; D002129:Calcium Oxalate; D000077337:Vorinostat