Changes in Microsomal Activity in Alcoholism and Obesity

Maza, M. P a de la; Hirsch, Sandra; Petermann, Marcus; Suazo, Myriam; Ugarte, G; Bunout, Daniel

doi:10.1097/00000374-200005000-00004

Cited by 13 publications

(15 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Induction of CYP2E1 in the liver of NAFLD patients with steatohepatitis was evidenced by the significant increase in its activity (p-NPH) and content (immunoblot analysis) [44], in agreement with studies assessing liver CYP2E1 by immunohistochemistry [21], and occurs regardless of changes in total cytochrome P450 content. Although obesity increases the activity of CYP2E1 in human liver, as shown by studies measuring the pharmacokinetics of chlorzoxazone [44][45][46] or the plasma levels of inorganic fluoride after exposure to halogenated anaesthetics [47], no correlation with liver injury was carried out. Furthermore, progressive functional deficiency associated with the development of liver injury, mainly protein synthesis, could also contribute to the lower activity of antioxidant enzymes found in patients with more advanced stages of NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients

et al. 2004

View full text Add to dashboard Cite

Oxidative stress is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). In the present study, hepatic and plasma oxidative stress-related parameters were measured and correlated with clinical and histological findings in 31 NAFLD patients showing increased body mass index. Liver protein carbonyl content was enhanced by 403% in patients with steatosis (n=15) compared with control values (n=12), whereas glutathione content, superoxide dismutase (SOD) activity and the ferric reducing ability of plasma (FRAP) were decreased by 57%, 48% and 21% (P<0.05) respectively. No changes in microsomal p-nitrophenol hydroxylation and the total content of cytochrome P450 (CYP) or CYP2E1 were observed. Patients with steatohepatitis (n=16) exhibited protein carbonyl content comparable with that of controls, whereas glutathione content, SOD and catalase activities were decreased by 27%, 64% and 48% (P<0.05). In addition, FRAP values in patients with steatohepatitis were reduced by 33% and 15% (P<0.05) when compared with controls and patients with steatosis respectively, whereas p-nitrophenol hydroxylation (52%) and CYP2E1 content (142%) were significantly increased (P<0.05) compared with controls. It is concluded that oxidative stress is developed in the liver of NAFLD patients with steatosis and is exacerbated further in patients with steatohepatitis, which is associated with CYP2E1 induction. Substantial protein oxidation is followed by proteolysis of the modified proteins, which may explain the co-existence of a diminished antioxidant capacity and protein oxidation in the liver of patients with steatohepatitis.

show abstract

Section: Discussionmentioning

confidence: 99%

Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients

et al. 2004

View full text Add to dashboard Cite

show abstract

“…The identification of polymorphic expressions of CYP2E1 in specific populations may contribute to alcohol-induced toxicity and the generation of steatosis in the liver. 57 Increased ethanol metabolism by induced CYP2E1 and production of reactive oxidative species has been suggested to be an initiating event in alcoholic liver injury. 58 Gene knockout mice are proving a useful tool for characterizing the role of a particular CYP in a toxicological response.…”

Section: Alcohol Metabolismmentioning

confidence: 99%

Alcohol Use and HIV Pharmacotherapy

Kresina

Flexner

Sinclair

et al. 2002

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Alcohol consumption by individuals infected with HIV is an important medical management issue with significant implications for the effectiveness of antiretroviral therapy as well as an important evolving field of HIV research. Alcohol consumption is a risk factor for poor medication adherence and can modify liver drug metabolism, both of which can lead to the emergence of drug-resistant virus. Research indicates that alcohol consumption greater than 50 g/day (four or five drinks) is a risk factor for liver disease progression among patients with HIV/HCV coinfection. In addition, alcohol-induced cirrhosis can result in changes in drug metabolism in the liver through compromised liver function. More research studies are needed to elucidate the biological and molecular basis of the clinical changes induced by alcohol consumption in HIV-infected individuals and on the relationship of these changes to the effectiveness of HIV pharmacotherapy. Specifically, research areas that are of particular importance are (1) determining alcohol consumption levels and patterns and its impact on antiretroviral medication adherence, efficacy, and physician prescribing practices; (2) identifying behavioral interventions to enhance adherence to HIV medications and reduce alcohol consumption; (3) clarifying the relationships and interactions among alcohol metabolism, HIV drug metabolism, and pharmacogenetics; (4) elucidating the extent of liver toxicity due to antiretroviral therapy and drug-drug interactions in individuals who consume alcohol; and (5) delineating the contribution of alcohol consumption to end-stage organ damage, particularly in HIV/HCV coinfection.

show abstract

“…Our finding of a positive relationship between body weight and CYP2E1 activity is in agreement with previous studies. 3,19,[55][56][57] O'Shea et al 3 reported that HCZ formation clearance was more than 50% higher in obese subjects with normal renal function than in control subjects. Lucas et al 55 reported similar results.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, obesity is a risk factor for alcohol-induced hepatotoxicity, 58 and recent studies have used CZ as a phenotypic probe in obese alcoholic subjects to estimate their susceptibility to hepatotoxicity. 19 Failure to appreciate the impact of renal function on the phenotypic trait measure in these types of subjects could confound the results, because increased weight in individuals with reduced renal function appears to have at least additive effects on the CZ MR (Fig 7). It still remains to be determined, however, whether the inclusion of weight in the population model reported here was merely a surrogate for organ size or whether there are additional effects of obesity on CL f .…”

Section: Discussionmentioning

confidence: 99%

“…2,12,14,17 Although it is currently of limited use therapeutically, CZ is used extensively as a phenotypic probe because of its relative safety and selectivity for CYP2E1. 10 It has been used in several studies assessing the impact of various conditions 2,3,10,13,18,19 and pharmacotherapy 20-23 on CYP2E1 activity. CZ currently remains the only validated pharmacologic probe for CYP2E1 in humans.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Impaired 6-hydroxychlorzoxazone elimination in patients with kidney disease: implication for cytochrome P450 2E1 pharmacogenetic studies

Nolin¹,

Gastonguay²,

Bies³

et al. 2003

Clinical Pharmacology & Therapeutics

View full text Add to dashboard Cite

Although cytochrome P450 (CYP) 2E1 activity, as estimated by 6-hydroxychlorzoxazone formation clearance, was not affected by kidney disease, the chlorzoxazone metabolic ratio was substantially elevated in these subjects. The results of this study show that the commonly used plasma-based chlorzoxazone metabolic ratio is dependent on renal function and, therefore, does not provide a reliable index of CYP2E1-mediated metabolism.

show abstract

Changes in Microsomal Activity in Alcoholism and Obesity

Abstract: Centripetal adiposity and alcoholism are associated with induction of CYP2E1. This may explain the higher prevalence of liver damage among obese alcoholics and also nonalcoholic steatohepatitis.

Cited by 13 publications

References 45 publications

Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients

Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients

Alcohol Use and HIV Pharmacotherapy

Impaired 6-hydroxychlorzoxazone elimination in patients with kidney disease: implication for cytochrome P450 2E1 pharmacogenetic studies

Contact Info

Product

Resources

About