Dissertation
ROLE OF OXIDATIVE STRESS IN THE NEPHROTOXICITY AND HEPATOTOXICITY OF OCHRATOXIN A
Doctor of Philosophy (PhD), Washington State University
01/2017
Handle:
https://hdl.handle.net/2376/117280
Abstract
Ochratoxin A (OTA) is a mycotoxin produced by species in the genera Aspergillus and Penicillium. OTA is commonly found in a wide range of food, such as cereals, nuts, wine, and coffee beans. OTA is a potent renal carcinogen and hepatotoxicant that is currently classified as a possible carcinogen to humans (Group 2B). However, the mechanism by which OTA exerts its toxicity is not clear. Therefore, the overall objective of this study was to investigate the role of oxidative stress in OTA-mediated nephrotoxicity and hepatotoxicity. When the involvement of OTA to induce oxidative stress in human (HK-2) and pig (LLC-PK1) renal cells was studied, OTA was found to be 8-fold more toxic to HK-2 than LLC-PK1 at 72 h, and may induce oxidative stress in humans’ but not in pigs’ renal cells as evidenced by the increase in ROS production, depletion of glutathione, and modulation of the mRNA levels of antioxidant enzymes. OTA was also toxic to human liver (HepG2) cells by inducing oxidative stress. In addition, OTA induced oxidative stress in male ICR mice fed a cultured oat-based diet for 4 or 8 weeks. Renal or hepatic damage was not observed after 4 or 8 weeks as assessed by organ weights and serum biochemical parameters. However, OTA significantly inhibited the mRNA expression levels of catalase, glutathione peroxidase 1 (GPX1), superoxide dismutase 1, glutathione reductase (GSR), and hexose-6-phosphate dehydrogenase (H6PD) in both the kidney and liver of OTA-treated mice after 4 weeks. The mRNA levels of GPX1, GSR, and H6PD remained significantly low in the kidney of OTA-treated mice after 4 weeks, suggesting that OTA is contributing to a reduction in antioxidant defenses. Overall, the results presented in this dissertation support previous finding indicating that oxidative stress is a contributing factor in OTA-mediated nephrotoxicity and hepatotoxicity.
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Details
- Title
- ROLE OF OXIDATIVE STRESS IN THE NEPHROTOXICITY AND HEPATOTOXICITY OF OCHRATOXIN A
- Creators
- Enrique Garcia Perez
- Contributors
- DOJIN RYU (Advisor)ANDRZEJ J PASZCZYNSKI (Committee Member)GREGORY MÖLLER (Committee Member)ONESMO B BALEMBA (Committee Member)BARBARA RASCO (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- School of Food Science
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 208
- Identifiers
- 99900581429401842
- Language
- English
- Resource Type
- Dissertation