Honors College Thesis
 

The role of CYP2E1 and CYP4A in the development of non-alcoholic steatohepatitis

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  • Non-alcoholic Steatohepatitis (NASH) is an emerging form of liver disease associated with obesity, type II diabetes and dyslipidemia. As the prevalence of these metabolic conditions increases, so too has the occurrence of NASH in all sectors of the population. The pathology of this disease is similar to its alcoholic form, however the cause leading from a steatotic liver to NASH has yet to be discovered. In recent studies the role of oxidative stress in the development of NASH has been identified as one of the possible mechanisms by which steatosis transitions to hepatitis. A major source of oxidative stress in the liver is the cytochrome P450 proteins (CYPs) that are involved in fatty acid hydroxylation. In this study brain derived neurotrophic factor knock-out mice that exhibit mature onset obesity and hyperinsulinemia were used to measure the levels of CYP2E1 and CYP4A in comparison with their non-obese counterparts. The levels of these enzymes and their activity were measured using western blot analysis and enzymatic activity assays. The levels of lipid peroxidation were also measured. From these results it was seen that the levels of CYP2E1 were not dramatically increased in the obese mice and the levels of CYP4A and lipid peroxidation were slightly increased, but with a high degree of variability among the samples.
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