The thioredoxin system as a target for mercury compounds.

Area of Science:

• Biochemistry
• Toxicology
• Environmental Health

Background:

• Mercury's interaction with selenium in vivo is known, but selenium's protective effects against mercury toxicity are controversial.
• Selenoproteins, like the selenoenzyme thioredoxin reductase (TrxR), are potential targets for mercury toxicity due to mercury's high affinity for selenols.
• The thioredoxin system, including TrxR, is crucial for cellular function, making its interaction with mercury a key factor in mercury-induced cell death.

Purpose of the Study:

• To review the interaction between mercury compounds and the thioredoxin system.
• To discuss the implications for mercury toxicity development.
• To examine the effects of selenium co-exposure on mercury toxicity.

Main Methods:

• Literature review of existing research on mercury-selenium interactions.
• Analysis of the molecular mechanisms of mercury toxicity.
• Evaluation of cellular compensation pathways and their role in mitigating toxicity.

Main Results:

• Mercury toxicity initiates with the inhibition of the selenoenzyme TrxR.
• Selenium supplementation offers partial protection against inorganic mercury (Hg(II)) but not methylmercury.
• Cell death occurs when alternative reduction pathways for thioredoxin (involving glutathione and glutaredoxin) are overwhelmed after TrxR inhibition.

Conclusions:

• Understanding mercury's molecular toxicity mechanisms and enzymatic compensation is vital for developing mitigation strategies.
• Altered activity or expression of TrxR and thioredoxin (Trx) in plasma could serve as future biomarkers for mercury toxicity.
• These biomarkers could enhance the accuracy of mercury risk assessment processes.