title: Drug metabolism enzymes in a steatotic model of rat treated with a high fat diet and a low dose of streptozotocin.
abstract: Herein we have characterized CYPs and antioxidant enzymes in a new steatotic rat model induced with a high fat diet (HFD) combined with a low dose of streptozotocin (STZ). This model was recently put forward in order to better replicate the NAFLD human pathology. HFD/STZ rats developed hyperglycemia, hypercholesterolemia and overt steatosis. The treatment also caused liver damage, but not lipid peroxidation, suggesting this damage was due to hepatic fat deposition and excess formation of toxic free fatty acids, rather than to oxidative stress. In the HFD/STZ group, a significant rise in total CYP content was found, in conjunction with increased activity and protein levels of CYP2E1 and CYP4A, the latter also up-regulated at the transcriptional level. A significant decrease of CYP2C11 was observed at the transcriptional and protein level, whereas CYP3A2 did not change in response to HFD/STZ treatment. In our experimental conditions, the activity of the HO-1 and NQO1 enzymes, whose genes are regulated by Nrf2, were not affected, and nor were the antioxidant enzymes SOD and CAT, confirming the lack of oxidative stress. Our HFD/STZ treatment, which established overt steatosis and changes in CYPs expression, but not oxidative stress, likely reflects an early stage of NAFLD.
authors.affiliation: Institute of Clinical Physiology, CNR, via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Vornoli
authors.affiliation: Institute of Agricultural Biology and Biotechnology, CNR, via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Pozzo
authors.affiliation: Institute of Agricultural Biology and Biotechnology, CNR, via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: C M
authors.initials: CM
authors.lastname: Della Croce
authors.affiliation: Institute of Clinical Physiology, CNR, via Moruzzi 1, 56124 Pisa, Italy.
authors.forename: P G
authors.initials: PG
authors.lastname: Gervasi
authors.affiliation: Institute of Agricultural Biology and Biotechnology, CNR, via Moruzzi 1, 56124 Pisa, Italy. Electronic address: v.longo@ibba.cnr.it.
authors.forename: V
authors.initials: V
authors.lastname: Longo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy / Q000201:enzymology*; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin / Q000008:administration & dosage / Q000009:adverse effects*; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D014280:Triglycerides; D013311:Streptozocin; D002784:Cholesterol; D019392:Cytochrome P-450 CYP2E1; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D042926:Cytochrome P-450 CYP4A; D016660:NAD(P)H Dehydrogenase (Quinone); C507703:NQO1 protein, rat
keywords: Cytochrome P450; High-fat diet; Rat; Steatosis; Streptozotocin; Type 2 diabetes