P130 Acrylamide Induction of CYP2E1 in the Rabbit Liver

Mine Nuyan Akkeçi , Biological Sciences, Middle East Technical University, Ankara, Turkey
Sevki Arslan , Biological Sciences, Middle East Technical University, Ankara, Turkey
Çigdem Kalin , Biological Sciences, Middle East Technical University, Ankara, Turkey
Emel Arinç , Biological Sciences, Middle East Technical University, Ankara, Turkey
Acrylamide is a neurotoxin, reproductive toxin and carcinogen in animals and a potential food carcinogen in humans.  Presence of high concentration of acrylamide in some food products including processed potato products, bread, cereals, cookies, and snacks has triggered   worldwide concern on acrylamide toxicity. Acrylamide is formed  during starch food processing at high temperatures by the Mailard reaction utilizing reducing sugars and amino acid, asparagine. The epoxidation of acrylamide to its epoxide glycidamide by CYP2E1 in the acrylamide metabolism is mostly attributed to be responsible for carcinogenicity of acrylamide. However, the effect of acrylamide on cytochrome P450 isozymes have not been investigated yet. The present study aimed to investigate in vivo effects of acrylamide on CYP2E1 protein levels and associated enzyme activities in rabbit liver. Administration of  acrylamide  (100mg/kg s.c., on day 1, 5 and 8) to  New Zealand male rabbits was found to elevate hepatic  microsomal CYP2E1 protein levels, significantly, as determined by Western Blot analysis, by 2-fold. In addition, CYP2E1-dependent p-nitrophenol hydroxylase, NDMA-N-demethylase and aniline 4-hydroxylase activities were significantly increased approximately 1.80 to 3.0 fold in acrylamide-treated rabbit liver compared to controls. Among the liver damage marker enzymes, no change was observed in alanine amino transferase (ALT) and aspartate amino transferase (AST) enzyme activities, whereas acrylamide treatment led to a significant increase in sorbitol dehydrogenase (SDH) activities in both blood serum and liver (1.68- and 1.27-fold, respectively) with respect to controls. The results of the present study demonstrated for the first time that acrylamide treatments induced CYP2E1 protein level and associated enzyme activities in rabbit liver. In conclusion, it has been suggested that the induction of CYP2E1 enzyme due to acrylamide exposure may stimulate not only the formation of epoxide glycidamide, but the activation of other xenobiotics metabolized by CYP2E1 such as nitrosamines, benzene, and pyridine, leading to further increase in mutagenicity and carcinogenicity of these chemicals.

Acknowledgment: Partly supported by Turkish Academy of Sciences

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