title: Comparison of long-term impact of immunosuppressants at therapeutic doses on hepatic function and histological changes in unilateral nephrectomized rats.
abstract: Cyclosporine, tacrolimus and sirolimus are commonly used in renal transplant recipients to prevent rejection. Various adverse effects of these agents on the multiple organ system have been reported clinically. However, animal studies are necessary to determine and compare these effects on individual organ given the presence of multiple confounding factors and multi-pharmacy in clinical settings. In a physiologically and clinically relevant rat model of unilateral nephrectomy, the long-term impacts of commonly used immunosuppressants at doses equivalent to the therapeutic levels used for post-renal transplant patients on hepatic function and histological changes of the liver were examined. Cyclosporine induced significant hepatocellular injury, impairment of synthetic function of the liver, hyperbilirubinemia and cholestasis, and dyslipidemia accompanied by profound histological changes of hepatic structures on both light and electron microscopic examinations. On the other hand, neither tacrolimus nor sirolimus developed any hepatotoxic effects except for more remarkable dyslipidemia was observed in animals treated with sirolimus. Our study indicates that long-term administration of commonly used immunosuppressants has various impacts on biochemical parameters as well as histological alterations of the liver even at therapeutic levels. These data may therefore provide useful information for judicious selection of immunosuppressive agents based on different clinical settings.
authors: Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China. Electronic address: cyhly@163.com.
authors: Yehui
authors: Y
authors: Chen
authors: Department of Urology, Yangjiang People's Hospital, 42 Dongshan Road, Yangjiang, Guangdong 529500, People's Republic of China.
authors: Huaxin
authors: H
authors: Lin
authors: Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
authors: Zhi
authors: Z
authors: Zhang
authors: Reproductive Center, Guangdong General Hospital, Guangdong Academy of Medical Science, Guangzhou, Guangdong 510080, People' Republic of China.
authors: Yun
authors: Y
authors: Lin
authors: Laboratory of Electron Microscope, Southern Medical University, Guangzhou, Guangdong 510450, People's Republic of China.
authors: Yanmeng
authors: Y
authors: Lu
authors: Department of Andrology, Zhongshan People's Hospital, Sun Yat-sen University, 2 Sunwen East Road, Zhongshan, Guangdong 528403, People's Republic of China.
authors: Runqiang
authors: R
authors: Yuan
authors: Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
authors: Miaoyuan
authors: M
authors: Li
authors: Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
authors: Pin
authors: P
authors: Nie
authors: Department of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China.
authors: Lizhong
authors: L
authors: Chen
authors: Department of Organ Transplantation, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510080, People's Republic of China.
authors: Jiang
authors: J
authors: Qiu
authors: Department of Laboratory Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
authors: Linqiang
authors: L
authors: Chen
authors: Department of Laboratory Medicine, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
authors: Banglao
authors: B
authors: Xu
authors: Department of Pathology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
authors: Wuzhou
authors: W
authors: Lin
authors: Department of Pathology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
authors: Jin
authors: J
authors: Xu
authors: Department of Pathology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
authors: Hong
authors: H
authors: Du
authors: Department of Pharmacy, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, People's Republic of China.
authors: Jianjian
authors: J
authors: Liang
authors: Division of Nephrology, Department of Medicine, VA Loma Linda Healthcare System and Loma Linda University, Loma Linda, CA 92357, United States. Electronic address: zhiwei.zhang@va.gov.
authors: Zhiwei
authors: Z
authors: Zhang
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000633:toxicity*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000633:toxicity*; D016030:Kidney Transplantation; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000633:toxicity*; D016559:Tacrolimus / Q000633:toxicity*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus
keywords: Immunosuppressant; Kidney; Liver; Rat