Drug Glutathione peroxidase

Roberts,J.(1993)Thekineticpropertiesof Au(I) drug binding to serum albumin and selenium-glutathione peroxidase and their significance for rheumatoid arthritis. Ph.D. thesis, University-Milwaukee. 

Garlic s proven mechanisms of action include (a) inhibition of platelet function, (b) increased levels of two antioxidant enzymes, catalase and glutathione peroxidase, and (c) inhibition of thiol enzymes such as coenzyme A and HMG coenzyme A reductase. Garlic s anti-hyperlipidemic effects are believed to be in part due to the HMG coenzyme A reductase inhibition since prescription medications for hyperlipidemia have that mechanism of action (statins). It is unknown whether garlic would have the same drug interactions, side effects, and need for precautions as the statins. 

The only selenium-containing drug candidate is ebselen (Figure 15.71) which owes its antioxidant and antiinflammatory properties to its interference with the selenoenzyme glutathione-peroxidase. Because of its strongly bound selenium moiety only metabolites of low toxicity are formed. 

The oxidants are products of normal cellular respiration that are normally counterbalanced by an antioxidant defense system that prevents tissue destruction. The antioxidants include superoxide dismutase, catalase, glutathione peroxidase, ceruloplasmin, and a-tocopherol (vitamin E). Antioxidants are ubiquitous in the body. Hy-peroxia produces toxicity by overwhelming the antioxidant system. There is experimental evidence that a number of drugs and chemicals produce lung toxicity through increasing production of oxidants (e.g., bleomycin, cyclophosphamide, nitrofurantoin, and paraquat) and/or by inhibiting the antioxidant system (e.g., carmustine, cyclophosphamide, and nitrofurantoin). ... 

As the drug enters a cell, it forms superoxide anions. These free radicals (e.g., hydrogen peroxide) normally are destroyed by glutathione peroxidase however, this enzyme, and the required glutathione, is of limited concentration in cardiac cells. Thus, the radicals complex with available I c ions, forming highly reactive radicals that rapidly cause lipid peroxidation and extensive mitochondrial destruction. 

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