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Dichloroacetate Accelerates Autosomal Recessive Polycystic Kidney Disease in the Pck Rat
Author(s) -
Gattone Vincent H.,
Sinders Rachel
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1123.9
Subject(s) - polycystic kidney disease , kidney , medicine , endocrinology , histopathology , apoptosis , kidney disease , disease , pathology , biology , biochemistry
Dichloroacetate‐DCA is found in chlorinated water and known to be toxic in high doses. DCA is also promoted as a cancer chemotherapeutic agent at low doses, causing an increase in apoptosis of malignant cells and leaving nontransformed cells unaffected. Some chemotherapeutic drugs ameliorate the renal pathology in Polycystic Kidney Disease‐PKD. PKD typically affects both liver and kidney. Renal and biliary epithelia usually exhibits increased proliferation and apoptosis. In the present study we hypothesized that DCA might modify the PKD in Pck rats, an orthologous model of human autosomal recessive PKD. DCA was added to drinking water (75mg/l, a relatively low dose) for 4 week‐old male and female Pck rats, while control rats received tap water. At 8 weeks, rats were evaluated for renal and liver histopathology and serological evidence of disease. Treated male rats had an increased body weight, total kidney weight, volume of renal cystic change and increased proteinuria, but without evidence of increased liver disease. Interestingly, hepatorenal disease in females was unaffected by DCA treatment. In conclusion, data indicated DCA causes an increase in severity of renal disease in male Pck rats.