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Study on metabolism of plant carcinogen aristolochic acid I
Dedíková, Alena
Aristolochic acids (AA) are natural compounds present in plant species of Aristolochiaceae. These plant alkaloids exhibit nephrotoxic effects and are human carcinogens. The extract of plants species Aristolochiaceae contains various kinds of substances, including aristolochic acids. Aristolochic acid I (AAI) and aristolochic acid II (AAII) are mainly present. AA compounds are associated with two diseases, Aristolochic Acid Nephropathy (ANN), previously known as Chinese Herbs Nephropathy (CHN) and Balkan Endemic Nephropathy (BEN). Both these diseases are accompanied by renal failure and the formation of tumors in urothelial tissue, which are caused by AA. However, the same clinical manifestations do not occur in both diseases. This is propably due to the variability in enzymes involved in AA biotransformation, but also depends on AA doses. In organisms, AA are metabolized by activation and/or detoxification reactions. These thesis is directed on the activating metabolism of AAI, precisely to clarify the formation of reducing metabolites of AAI. Reduction of AAI is the activation pathway responsible for the genotoxic effect of AAI. During this reaction AAI is enzymatically reduced to the cyclic acylnitrenium ion that is capable of binding to the exocyclic amino groups of adenine and guanine in DNA...
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Study on metabolism of plant carcinogen aristolochic acid I
Dedíková, Alena ; Stiborová, Marie (advisor) ; Eckschlager, Tomáš (referee)
Aristolochic acids (AA) are natural compounds present in plant species of Aristolochiaceae. These plant alkaloids exhibit nephrotoxic effects and are human carcinogens. The extract of plants species Aristolochiaceae contains various kinds of substances, including aristolochic acids. Aristolochic acid I (AAI) and aristolochic acid II (AAII) are mainly present. AA compounds are associated with two diseases, Aristolochic Acid Nephropathy (ANN), previously known as Chinese Herbs Nephropathy (CHN) and Balkan Endemic Nephropathy (BEN). Both these diseases are accompanied by renal failure and the formation of tumors in urothelial tissue, which are caused by AA. However, the same clinical manifestations do not occur in both diseases. This is propably due to the variability in enzymes involved in AA biotransformation, but also depends on AA doses. In organisms, AA are metabolized by activation and/or detoxification reactions. These thesis is directed on the activating metabolism of AAI, precisely to clarify the formation of reducing metabolites of AAI. Reduction of AAI is the activation pathway responsible for the genotoxic effect of AAI. During this reaction AAI is enzymatically reduced to the cyclic acylnitrenium ion that is capable of binding to the exocyclic amino groups of adenine and guanine in DNA...
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