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T-2 toxin-induced DNA damage in mouse livers: the effect of pretreatment with coenzyme Q10 and alpha-tocopherol
1Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Helsinki, Finland.
Abstract:
Active oxygen species are reported to cause organ damage. This study was therefore designed to determine whether oxidative stress contributed to the initiation or progression of hepatic DNA damage produced by T-2 toxin. The aim of the study was also to investigate the behaviour of the antioxidants coenzyme Q10 (CoQ10), and alpha-tocopherol (vitamin E) against DNA damage in the livers of mice fed T-2 toxin. Treatment of fasted mice with a single dose of T-2 toxin (1.8 or 2.8 mg/kg body weight) by oral gavage led to 76% hepatic DNA fragmentation. T-2 toxin also decreased hepatic glutathione (GSH) levels markedly. Pretreatment with CoQ10 (6 mg/kg) together with alpha tocopherol (6 mg/kg) decreased DNA damage. The CoQ10 and vitamin E showed some protection against toxic cell death and glutathione depletion caused by T-2 toxin. Oxidative damage caused by T-2 toxin may be one of the underlying mechanisms for T-2 toxin-induced cell injury and DNA damage, which eventually lead to tumourigenesis.
Insights
T-2 toxin causes significant liver DNA damage and depletes glutathione. Antioxidants coenzyme Q10 (CoQ10) and alpha-tocopherol (vitamin E) offered protection against T-2 toxin-induced hepatic DNA damage and cell death.
Area of Science:
- Toxicology
- Hepatology
- Biochemistry
Background:
- Active oxygen species are implicated in organ damage.
- T-2 toxin is a known mycotoxin that can cause cellular injury.
Purpose of the Study:
- To investigate the role of oxidative stress in T-2 toxin-induced hepatic DNA damage.
- To evaluate the protective effects of coenzyme Q10 (CoQ10) and alpha-tocopherol (vitamin E) against T-2 toxin-induced liver damage.
Main Methods:
- Mice were administered single oral doses of T-2 toxin (1.8 or 2.8 mg/kg).
- Hepatic DNA fragmentation and glutathione (GSH) levels were measured.
- Mice were pretreated with CoQ10 (6 mg/kg) and alpha-tocopherol (6 mg/kg) before T-2 toxin administration.
Main Results:
- T-2 toxin induced 76% hepatic DNA fragmentation.
- T-2 toxin significantly decreased hepatic GSH levels.
- CoQ10 and alpha-tocopherol pretreatment reduced DNA damage and GSH depletion.
Conclusions:
- Oxidative damage is a key mechanism in T-2 toxin-induced liver injury and DNA damage.
- CoQ10 and vitamin E demonstrate protective potential against T-2 toxin toxicity.
- T-2 toxin-induced hepatic DNA damage may contribute to hepatocarcinogenesis.
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