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The protective effects of hydroxytyrosol against ortho-phenylphenol-induced DNA damage in HepG2 cells
Jianqing Li1, Guang Yang, Shaopeng Wang
1Department of Food Nutrition and Safety, Dalian Medical University, Dalian, China.
Abstract:
Ortho-phenylphenol (OPP) has been found to cause carcinomas in the urinary tract of rats. Since OPP is a potent genotoxic compound, and used as fungicides and antibacterial agents in fruits and fruit products, search for newer, better agents for protection against toxicity of OPP is required. In this study, the chemoprotective effect of hydroxytyrosol (HT) against OPP-induced DNA damage in HepG2 cells was investigated. Comet assay was used to detect the DNA damage induced by OPP. To elucidate the possible mechanisms, we tested lysosomal membrane stability, mitochondrial membrane potential, intracellular generation of reactive oxygen species (ROS), and reduced glutathione (GSH). Results showed that HT significantly reduced the DNA strand breaks caused by OPP. Moreover, HT effectively suppressed OPP-induced ROS formation, and increased the GSH level. Lysosomal membrane and mitochondrial membrane were also protected when cells were pretreated with HT. These results suggested that the disruption of lysosomal membrane integrity and the oxidative stress, leading to DNA fragmentation, may be the mechanism of DNA damage induced by OPP. The antioxidant activity of HT may play an important part in attenuating the DNA damage of OPP.
Insights
Hydroxytyrosol (HT) protects against ortho-phenylphenol (OPP)-induced DNA damage by reducing oxidative stress and stabilizing cellular membranes. This study highlights HT as a potential chemoprotective agent against OPP toxicity.
Area of Science:
- Toxicology
- Cell Biology
- Biochemistry
Background:
- Ortho-phenylphenol (OPP) is a genotoxic compound used as a fungicide and antibacterial agent.
- OPP exposure is linked to urinary tract carcinomas in rats, necessitating research into protective agents.
- Understanding OPP's toxicity mechanisms is crucial for developing effective countermeasures.
Purpose of the Study:
- To investigate the chemoprotective effects of hydroxytyrosol (HT) against OPP-induced DNA damage in HepG2 cells.
- To elucidate the mechanisms underlying OPP-induced DNA damage and HT's protective role.
Main Methods:
- Comet assay was employed to quantify DNA strand breaks induced by OPP.
- Assessment of lysosomal membrane stability, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and reduced glutathione (GSH) levels.
- HepG2 cells were pretreated with HT before OPP exposure.
Main Results:
- HT significantly attenuated DNA strand breaks caused by OPP exposure.
- HT suppressed OPP-induced intracellular ROS generation and increased cellular GSH levels.
- HT pretreatment preserved lysosomal and mitochondrial membrane integrity.
Conclusions:
- OPP-induced DNA damage in HepG2 cells may involve lysosomal membrane disruption and oxidative stress.
- The antioxidant properties of HT play a key role in mitigating OPP-induced DNA damage.
- Hydroxytyrosol demonstrates significant chemoprotective potential against ortho-phenylphenol toxicity.
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