Jonathan P. Jackson

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Members of the cytochrome P450 (P450) enzyme families CYP1, CYP2, and CYP3 are responsible for the metabolism of approximately 75% of all clinically relevant drugs. With the increased prevalence of nonalcoholic fatty liver disease (NAFLD), it is likely that patients with this disease represent an emerging population at significant risk for alterations in(More)
CYP2C19 is a clinically important enzyme responsible for the metabolism of a number of therapeutic drugs, such as mephenytoin, omeprazole, diazepam, proguanil, propranolol and certain antidepressants. Genetic polymorphisms in this enzyme result in poor metabolizers of these drugs. There are racial differences in the incidence of the poor metabolizer trait,(More)
Many cytochrome P450 isoforms are known to be drug-inducible. The anticonvulsant phenytoin has been reported to be an inducer of human CYP2B6, CYP3A4, and murine CYP2C29. However, the molecular mechanism mediating phenytoin induction remains unclear. Herein, we used in vivo and in vitro gene reporter assays of the Cyp2c29 promoter to delineate the(More)
The CYP2C subfamily of cytochrome P450 monooxygenases is responsible for the metabolism of approximately 20% of therapeutic drugs and many endogenous compounds in humans. These enzymes can be induced by prior treatment with drugs, resulting in changes in drug efficacy. Induction of human CYP2C enzymes by xenobiotics occurs at the transcriptional level and(More)
Non-alcoholic steatohepatitis (NASH) is a disease that compromises hepatic function and the capacity to metabolize numerous drugs. Aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), pregnane X receptor (PXR), peroxisome proliferator-activated receptor alpha (PPARα), and nuclear factor-E2 related factor 2 (Nrf2) are xenobiotic activated(More)
Nonalcoholic fatty liver disease (NAFLD) is characterized by a series of pathological changes that range from simple fatty liver to nonalcoholic steatohepatitis (NASH). The objective of this study is to describe changes in global gene expression associated with the progression of human NAFLD. This study is focused on the expression levels of genes(More)
Oltipraz (OPZ) is a well known inducer of NAD(P)H:quinone oxidoreductase (NQO1) along with other enzymes that comprise the nuclear factor E2-related factor 2 (Nrf2) battery of detoxification genes. However, OPZ treatment also induces expression of CYP2B, a gene regulated by the constitutive androstane receptor (CAR). Therefore, this study was designed to(More)
Several compounds, including 2,10-dicarbethoxy-6-methoxy-5,7-dihydroindolo[2,3-b]carbazole (SR13668), (2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-napthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid (9-cis-UAB30), and 2,2,5,7,8-pentamethyl-6-chromanol (PMCol), were selected as promising chemopreventive agents and have entered preclinical trials for cancer(More)
Over the last decade HepaRG cells have emerged as a promising alternative to primary human hepatocytes (PHH) and have been featured in over 300 research publications. Most of these reports employed freshly differentiated HepaRG cells that require time-consuming culture (∼28 days) for full differentiation. Recently, a cryopreserved, predifferentiated format(More)
The ATP-binding cassette (ABC) family of transporters, including ABCC3, is a large family of efflux pumps that plays a pivotal role in the elimination of xenobiotics from the body. ABCC3 has been reported to be induced during hepatic stress conditions and through the progression of some forms of cancer. Several lines of evidence have implicated the(More)