Short- and medium-term impact of bariatric surgery on the activities of CYP2D6, CYP3A4, CYP2C9, and CYP1A2 in morbid obesity

Hong

et al. 2020

JCM

The impact of body mass index (BMI) on postoperative nausea and vomiting (PONV) is controversial, and few studies have focused on their relationship. We investigated the effects of BMI on PONV, taking into account other PONV risk factors. We analyzed adults over the age of 18 years who received general anesthesia between 2015 and 2019, using propensity score matching. Before propensity score matching, odds ratios (ORs) for PONV were lower for overweight (OR, 0.91; 95% confidence interval (CI), 0.87–0.96; p < 0.0001) or obese patients (OR, 0.77; 95% CI, 0.71–0.84; p < 0.0001) than for normal-BMI patients. After matching, the ORs for PONV of overweight (OR, 0.89; 95% CI, 0.80–0.98; p = 0.016) and obese patients (OR, 0.71; 95% CI, 0.63–0.79; p < 0.0001) were low. However, the ORs of underweight patients did not differ from those of normal-BMI patients, irrespective of matching. Therefore, the incidence of PONV may be lower among adults with a higher-than-normal BMI.

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of Body Mass Index on Postoperative Nausea and Vomiting: Propensity Analysis

Hong

et al. 2020

JCM

“…This contrasts with the mostly harmful effects of PXR action on the other components MetS (obesity, hypertension, glucose metabolism). However, as obesity is a major driver of the MetS and both CYP3A4 activity and circulating 4βHC are known to be repressed by obesity and MetS [ 69 , 70 ], the repression of hepatic CYP3A4–circulating 4βHC–peripheral LXR pathway could link obesity and disrupted HDL-C metabolism in the obese patients with MetS.…”

Section: Hdl Cholesterol Metabolism and The Pxr—4βhc Axismentioning

confidence: 99%

PXR and 4β-Hydroxycholesterol Axis and the Components of Metabolic Syndrome

Hukkanen

Hakkola

2020

Cells

Pregnane X receptor (PXR) activation has been found to regulate glucose and lipid metabolism and affect obesity in response to high-fat diets. PXR also modulates vascular tone. In fact, PXR appears to regulate multiple components of metabolic syndrome. In most cases, the effect of PXR action is harmful to metabolic health, and PXR can be hypothesized to play an important role in metabolic disruption elicited by exposure to endocrine-disrupting chemicals. The majority of the data on the effects of PXR activation on metabolic health come from animal and cell culture experiments. However, randomized, placebo-controlled, human trials indicate that the treatment with PXR ligands impairs glucose tolerance and increases 24-h blood pressure and heart rate. In addition, plasma 4β-hydroxycholesterol (4βHC), formed under the control of PXR in the liver, is associated with lower blood pressure in healthy volunteers. Furthermore, 4βHC regulates cholesterol transporters in peripheral tissues and may activate the beneficial reverse HDL cholesterol transport. In this review, we discuss the current knowledge on the role of PXR and the PXR–4βHC axis in the regulation of components of metabolic syndrome.

“…Phase I enzymes (Cytochrome P450 and flavin‐containing monooxygenases (FMOs)) serve to make drug compounds more soluble as the majority of drugs come in a lipophilic form. These enzymes are involved in the metabolism of the vast majority of pharmaceuticals (~75% of all marketed drugs) 8 . After a drug goes through a phase I enzyme‐catalysed conversion, its metabolite enters the phase II drug metabolism cycle driven by one of the phase II enzymes (UDP‐dependent glucuronosyltransferases (UGT), sulfotransferases (SULTs), N ‐acetyltransferases (NATs) and glutathione S ‐transferases (GSTs)).…”

Section: Introductionmentioning

confidence: 99%

“…These enzymes are involved in the metabolism of the vast majority of pharmaceuticals (~75% of all marketed drugs). 8 After a drug goes through a phase I enzyme-catalysed conversion, its metabolite enters the phase II drug metabolism cycle driven by one of the phase II enzymes (UDP-dependent glucuronosyltransferases (UGT), sulfotransferases (SULTs), N-acetyltransferases (NATs) and glutathione S-transferases (GSTs)). Phase II enzymes increase the solubility of drug metabolites in water and facilitate their subsequent excretion.…”

Section: Introductionmentioning

confidence: 99%

Liver microphysiological platforms for drug metabolism applications

Kulsharova

Kurmangaliyeva

2021

Cell Proliferation

Drug development is a costly and lengthy process with low success rates. To improve the efficiency of drug development, there has been an increasing need in developing alternative methods able to eliminate toxic compounds early in the drug development pipeline. Drug metabolism plays a key role in determining the efficacy of a drug and its potential side effects. Since drug metabolism occurs mainly in the liver, liver cell‐based alternative engineering platforms have been growing in the last decade. Microphysiological liver cell‐based systems called liver‐on‐a‐chip platforms can better recapitulate the environment for human liver cells in laboratory settings and have the potential to reduce the number of animal models used in drug development by predicting the response of the liver to a drug in vitro. In this review, we discuss the liver microphysiological platforms from the perspective of drug metabolism studies. We highlight the stand‐alone liver‐on‐a‐chip platforms and multi‐organ systems integrating liver‐on‐a‐chip devices used for drug metabolism mimicry in vitro and review the state‐of‐the‐art platforms reported in the last few years. With the development of more robust and reproducible liver cell‐based microphysiological platforms, the drug development field has the potential of reducing the costs and lengths associated with currently existing drug testing methods.