Modulation of cytochrome P450 enzymes in response to continuous or intermittent high-fat diet in pigs

Puccinelli, E.; Gervasi, Pier Giovanni; Pelosi, Gualtiero; Puntoni, M.; Longo, Vincenzo

doi:10.3109/00498254.2012.756558

Cited by 12 publications

(9 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The serum AST level was increased in CHF group only and not in the IHF group, whereas no changes were found in serum ALT levels between groups. Since ALT is considered a specific marker of liver damage, whereas AST is also present in many other tissues, we concluded that pig livers are not significantly damaged after the administration of a shortterm high-fat diet, as reported in a previous paper (Puccinelli et al, 2012). Obviously, these results need to be further investigated in future studies, increasing the number of animals.…”

Section: Discussionmentioning

confidence: 72%

Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

Puccinelli

Gervasi

Trivella

et al. 2015

Animal

View full text Add to dashboard Cite

A high-fat diet is known to induce atherosclerosis in animal models. Dietary factors and timing of atherogenic food delivery may affect plasma lipoprotein content composition and its potential atherogenic effect. Increasingly often, humans spend periods/days eating in a completely unregulated way, ingesting excessive amounts of food rich in oils and fats, alternating with periods/days when food intake is more or less correct. We investigate the effect on lipid homeostasis of a high-fat diet administered either continuously or intermittently. We investigated control pigs receiving standard diet (C, n = 7), pigs receiving a high-fat diet every day for 10 weeks (CHF, n = 5), and pigs receiving a high-fat diet every other week for 10 weeks (IHF, n = 7). IHF animals were shown to have a different lipid profile compared with CHF animals, with a significant increase in high-density lipoproteins (HDL) levels with respect to C and CHF groups. CHF also showed significantly higher values of TC/HDL cholesterol compared with C and IHF. Hepatic expression analysis of genes involved in lipid homeostasis showed an increasing trend of nuclear receptor LXRα along with its target genes in the CHF group and in the IHF group, whereas SREBP2 and LDLr were significantly inhibited. A significant correlation was found between ABCA1 expression and circulating levels of HDL-C. Periodic withdrawals of a high-fat atherogenic diet compared with a regular administration results in a different adaptive response of lipoprotein metabolism, which leads to a significantly higher plasma level of HDL-C and lower TC/HDL-C.

show abstract

Section: Discussionmentioning

confidence: 72%

Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

Puccinelli

Gervasi

Trivella

et al. 2015

Animal

View full text Add to dashboard Cite

show abstract

“…In addition to curbing obesity associated with high-fat diet, knocking out the CYP2E1 expression resulted in improved lipid profile in animals as indicated by decreased plasma triglyceride and free fatty acid levels compared to wild type control animals. In a different study, induction of hepatic CYP2E1 activity has also been reported in pigs, which were subjected to two-months of continuous high-fat/high-cholesterol diet compared to the control group of animals [164]. In another study, CYP2E1 has been shown to play a central role in the development of high-fat mediated non-alcoholic steatohepatitis, via induction of oxidative stress, further underscoring the involvement of CYP2E1 in high-fat diet mediated metabolic abnormalities [165].…”

Section: Das: Potential Protection Against Diseasesmentioning

confidence: 99%

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

Rao¹,

Midde²,

Miller³

et al. 2015

CDM

View full text Add to dashboard Cite

Diallyl sulfide (DAS) and other organosulfur compounds are chief constituents of garlic. These compounds have many health benefits, as they are very efficient in detoxifying natural agents. Therefore, these compounds may be useful for prevention/treatment of cancers. However, DAS has shown appreciable allergic reactions and toxicity, as they can also affect normal cells. Thus their use as in the prevention and treatment of cancer is limited. DAS is a selective inhibitor of cytochrome P450 2E1 (CYP2E1), which is known to metabolize many xenobiotics including alcohol and analgesic drugs in the liver. CYP2E1-mediated alcohol/drug metabolism produce reactive oxygen species and reactive metabolites, which damage DNA, protein, and lipid membranes, subsequently causing liver damage. Several groups have shown that DAS is not only capable of inhibiting alcohol- and drug-mediated cellular toxicities, but also HIV protein- and diabetes-mediated toxicities by selectively inhibiting CYP2E1 in various cell types. However, due to known DAS toxicities, its use as a treatment modality for alcohol/drug- and HIV/diabetes-mediated toxicity have only limited clinical relevance. Therefore, effort is being made to generate DAS analogs, which are potent and selective inhibitor of CYP2E1 and poor substrate of CYP2E1. This review summarizes current advances in the field of DAS, its anticancer properties, role as a CYP2E1 inhibitor, preventing agent of cellular toxicities from alcohol, analgesic drugs, xenobiotics, as well as, from diseases like HIV and diabetes. Finally, this review also provides insights toward developing novel DAS analogues for chemical intervention of many disease conditions by targeting CYP2E1 enzyme.

show abstract

“…Other variables that affect phase I/II enzymes include not only specific nutrients but the amount of nutrients. Obese animals have been shown to have decreased levels of CYP, although not all CYPs are affected (Ghose et al 2011), and variations exist between studies (Puccinelli et al 2013). The maternal diet also has been shown to have an effect on cytochrome levels via epigenetic regulation (Cai et al 2014;Cong et al 2012).…”

Section: Discussionmentioning

confidence: 99%

“…CYP mRNA levels can change with age and may vary between sexes (Sakuma et al 2004;Skaanild and Friis 1997;Vaclavikova et al 2004). Other variables in CYP diversity include epigenetics and diet (Antonovic and Martinez 2011), with dietary fat shown to modulate CYP in pigs via transcriptional and posttranscriptional mechanisms (Puccinelli et al 2013).…”

Section: Drug Metabolism Reactionsmentioning

confidence: 99%

Pigs in Toxicology

et al. 2016

View full text Add to dashboard Cite

Both a rodent and a nonrodent species are required for evaluation in nonclinical safety studies conducted to support human clinical trials. Historically, dogs and nonhuman primates have been the nonrodent species of choice. Swine, especially the miniature swine or minipigs, are increasingly being used in preclinical safety as an alternate nonrodent species. The pig is an appropriate option for these toxicology studies based on metabolic pathways utilized in xenobiotic biotransformation. Both similarities and differences exist in phase I and phase II biotransformation pathways between humans and pigs. There are numerous breeds of pigs, yet only a few of these breeds are characterized with regard to both xenobiotic-metabolizing enzymes and background pathology findings. Some specific differences in these enzymes based on breed and sex are known. Although swine have been used extensively in biomedical research, there is also a paucity of information in the current literature detailing the incidence of background lesions and differences between commonly used breeds. Here, the xenobiotic-metabolizing enzymes are compared between humans and pigs, and minipig background pathology changes are reviewed with emphasis on breed differences.

show abstract

Modulation of cytochrome P450 enzymes in response to continuous or intermittent high-fat diet in pigs

Cited by 12 publications

References 66 publications

Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

Modulation of lipid homeostasis in response to continuous or intermittent high-fat diet in pigs

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

Pigs in Toxicology

Contact Info

Product

Resources

About