Age-Related Alterations in Blood Biochemical Characterization of Hepatorenal Function in the PCK Rat: A Model of Polycystic Kidney Disease.
PCK rats develop age-related polycystic kidney disease (PKD) and liver disease and have been used to investigate pharmacotherapies to ameliorate hepatorenal lesions for patients with PKD. The PCK rat may be useful to understand the possible susceptibility to hepatotoxicity observed in the patient with PKD having hepatic polycystic lesions. Therefore, the purpose of this study was to investigate the background blood biochemical changes that reflect the hepatorenal function of PCK rats as well as the terminal histopathology in order to determine whether this model would be suitable for extrapolating the susceptibility of hepatotoxicity in patients. The blood biochemical parameters of hepatorenal function and histopathology were investigated in PCK rats at ages 5 to 19 weeks and compared to those outcomes in the Sprague Dawley (SD) rat. There were notable blood biochemical changes possibly due to biliary dysgenesis in the PCK rat as early as 5 weeks of age. High levels of γ-glutamyl transpeptidase, alkaline phosphatase, alanine aminotransferase, and total bile acids persisted throughout the study compared to the SD rat. Increased aspartate aminotransferase, total bilirubin, and hyperlipidemia and a decrease in albumin were also evident at 10 to 19 weeks of age possibly due to progression of cholestatic liver dysfunction secondary to age-related liver cystic progression. Increased liver weights generally correlated with the severity of biliary and hepatic histopathological changes. In male PCK rats, age-related increases in blood urea nitrogen and creatinine at 10 to 19 weeks of age were observed, and the cystic progression was more severe than that in females. These data indicate that the PCK rat showed notable blood biochemical changes reflecting alteration of the liver function compared to the SD rat. Also, there was a large individual variation in these parameters possibly due to variable progression rate of biliary dysgenesis and subsequent liver damages in PCK rats.
Otsuka Pharmaceutical Co, Ltd, Tokushima Research Institute, Tokushima, Japan.
Yuichi
Y
Shimomura
Otsuka Pharmaceuticals, Rockville, MD, USA Brock Scientific Consulting, LLC, Montgomery Village, MD, USA billbrock@comcast.net.
William J
WJ
Brock
Otsuka Pharmaceutical Co, Ltd, Tokushima Research Institute, Tokushima, Japan.
Yuko
Y
Ito
Otsuka Pharmaceutical Co, Ltd, Tokushima Research Institute, Tokushima, Japan.
Katsumi
K
Morishita
D000375:Aging / Q000097:blood*; D000818:Animals; D001659:Biliary Tract / Q000473:pathology; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D018450:Disease Progression; D005260:Female; D041781:Jaundice, Obstructive / Q000503:physiopathology; D007668:Kidney / Q000473:pathology / Q000503:physiopathology*; D007677:Kidney Function Tests; D008099:Liver / Q000473:pathology / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D009929:Organ Size; D007690:Polycystic Kidney Diseases / Q000097:blood* / Q000473:pathology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003404:Creatinine
aging; hepatorenal dysfunction; inherited disease; large individual variation