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Updated: Jul 16, 2026
Cell Type-specific Gene Expression Profiling in the Mouse Liver
Published on: September 17, 2019
Gene expression analyses of the liver in rats treated with oxfendazole
Yasuaki Dewa1, Jihei Nishimura, Masako Muguruma
1Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu-shi, Tokyo, 183-8509, Japan. dewa@cc.tuat.ac.jp
Abstract:
The effect of oxfendazole (OX), a benzimidazole anthelmintic, on hepatic gene expression was investigated in the liver of rats as a preliminary study to elucidate the possible mechanism of its non-genotoxic hepatocarcinogenesis. The liver from a male F344/N rat given a diet containing 500 ppm of OX for 3 weeks was examined by global gene expression analysis in comparison with an untreated rat. Microarray analysis revealed that phase I and phase II detoxifying enzymes were up-regulated in an OX-treated rat. In addition to these genes, the expressions of several upregulated genes related to xenobiotic metabolism and oxidative stress [e.g. Cyp1a1; NAD(P)H dehydrogenase, quinone 1 (Nqo1); glutathione peroxidase 2 (Gpx2); glutathione S-transferase Yc2 subunit (Yc2)], were confirmed by real-time reverse transcription polymerase chain reaction (RT-PCR). Furthermore, rats were administered 500 or 1,000 ppm of OX for 9 weeks, and the effect of OX on oxidative stress responses was evaluated by real-time RT-PCR along with conventional toxicological assays, including lipid peroxidation (thiobarbituric acid-reactive substance; TBARS). A longer treatment period and/or a higher dose of OX tended to increase the gene expressions of not only phase I (Cyp1a1 and Cyp1a2) but also phase II (Nqo1, Gpx2, Yc2, and Akr7a3) drug metabolizing enzymes. Toxicological parameters, such as TBARS, serum aspartate aminotransferase (AST), and serum alkaline phosphatase (ALP), showed slight but significant increases after treatment with OX for 9 weeks. These results indicate that OX elicits adaptive responses against oxidative stress in the liver and suggest that the imbalance in redox status might be one of the factors triggering the initial step of OX-induced non-genotoxic carcinogenesis in the liver of rats.
Insights
Oxfendazole (OX) exposure in rats upregulates liver genes involved in detoxification and oxidative stress responses. This suggests that redox imbalance may initiate OX-induced non-genotoxic liver cancer.
Area of Science:
- Toxicology
- Hepatocarcinogenesis
- Gene Expression Analysis
Background:
- Benzimidazole anthelmintics like oxfendazole (OX) are used in veterinary medicine.
- Preliminary studies suggest OX may cause non-genotoxic hepatocarcinogenesis.
- Understanding the molecular mechanisms of OX-induced liver effects is crucial.
Purpose of the Study:
- To investigate the effect of OX on hepatic gene expression in rats.
- To elucidate the potential mechanism of OX-induced non-genotoxic hepatocarcinogenesis.
- To assess OX-induced oxidative stress responses in the liver.
Main Methods:
- Global gene expression analysis (microarray) in rat liver.
- Real-time reverse transcription polymerase chain reaction (RT-PCR) for gene expression validation.
- Toxicological assays including lipid peroxidation (TBARS), AST, and ALP measurements.
Main Results:
- OX treatment upregulated genes involved in phase I and phase II detoxification pathways.
- Upregulated genes included those related to xenobiotic metabolism and oxidative stress (e.g., Cyp1a1, Nqo1, Gpx2).
- Longer exposure and higher doses of OX amplified these gene expression changes and slightly increased TBARS, AST, and ALP levels.
Conclusions:
- OX elicits adaptive responses against oxidative stress in the rat liver.
- An imbalance in redox status may be an initial step in OX-induced non-genotoxic liver carcinogenesis.
- Further research is warranted to confirm these findings and their implications.
