title: Ochratoxin A induces rat renal carcinogenicity with limited induction of oxidative stress responses.
abstract: Ochratoxin A (OTA) has displayed nephrotoxicity and renal carcinogenicity in mammals, however, no clear mechanisms have been identified detailing the relationship between oxidative stress and these toxicities. This study was performed to clarify the relationship between oxidative stress and the renal carcinogenicity induced by OTA. Rats were treated with 70 or 210 μg/kg b.w. OTA for 4 or 13 weeks. In the rats administrated with OTA for 13 weeks, the kidney was damaged seriously. Cytoplasmic vacuolization was observed in the outer stripe of the outer medulla. Karyomegaly was prominent in the tubular epithelium. Kidney injury molecule-1 (Kim-1) was detected in the outer stripe of the outer medulla in both low- and high-dose groups. OTA increased the mRNA levels of clusterin in rat kidneys. Interestingly, OTA did not significantly alter the oxidative stress level in rat liver and kidney. Yet, some indications related to proliferation and carcinogenicity were observed. A dose-related increase in proliferating cell nuclear antigen (PCNA) was observed at 4 weeks in both liver and kidney, but at 13 weeks, only in the kidney. OTA down-regulated reactive oxygen species (ROS) and up-regulated vimentin and lipocalin 2 in rat kidney at 13 weeks. The p53 gene was decreased in both liver and kidney at 13 weeks. These results suggest that OTA caused apparent kidney damage within 13 weeks but exerted limited effect on oxidative stress parameters. It implies that cell proliferation is the proposed mode of action for OTA-induced renal carcinogenicity.
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
authors.forename: Xiaozhe
authors.initials: X
authors.lastname: Qi
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
authors.forename: Liye
authors.initials: L
authors.lastname: Zhu
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Gao
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083, China.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: He
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083, China.
authors.forename: Kunlun
authors.initials: K
authors.lastname: Huang
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083, China.
authors.forename: Yunbo
authors.initials: Y
authors.lastname: Luo
authors.affiliation: College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China; The Supervision, Inspection and Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083, China. Electronic address: xuwentao@cau.edu.cn.
authors.forename: Wentao
authors.initials: W
authors.lastname: Xu
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects*; D051152:Clusterin / Q000097:blood / Q000378:metabolism*; D020552:Comet Assay; D005978:Glutathione / Q000032:analysis; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009793:Ochratoxins / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity; D018384:Oxidative Stress / Q000502:physiology*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011916:Rats, Inbred F344; D017382:Reactive Oxygen Species / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000032:analysis
chemical_list: D015815:Cell Adhesion Molecules; D051152:Clusterin; D005978:Glutathione; D008315:Malondialdehyde; D009793:Ochratoxins; D012313:RNA; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; C110936:Havcr1 protein, rat; C025589:ochratoxin A
keywords: Cell proliferation; Nephrotoxicity; Ochratoxin A; Oxidative stress; Renal carcinogenicity