Study of the Urinary Ratio of 6 β-Hydroxycortisol/Cortisol as a Biomarker of CYP3A4 Activity in Egyptian Patients with Chronic Liver Diseases

ELDesoky, Ehab S.; Kamel, Sherif; Farghaly, Ahlam M.; Bakheet, Madiha Y.; Hedaya, Mohsen A.; Siest, Jean-Pascal

doi:10.1177/117727190600100003

Cited by 4 publications

(4 citation statements)

References 51 publications

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“…In addition, the specific molecular mechanisms by which P-gp/MRP2/CYP3A4 inhibitors are regulated in the intestines of PH rats remain unclear. It may be associated with the pregnane X receptor, retinoid X receptor alpha, protein kinase C, radixin protein, nuclear factor kB, human cAMP response element-binding protein or CAATT box enhancer binding protein, which are reported to be the key factors involved in regulating CYP3A4, P-gp or MRP2 (19,(27)(28)(29)(30)(31). Further studies are required to address these questions to ultimately achieve the oral absorption of OCT.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Sun

Duan

Liu

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. The aim of the present study was to increase the intestinal transport of octreotide (OCT) by targeting the first-pass impact to identify a potential method for decreasing portal vein pressure (PVP) using oral OCT. Thus, the bioavailability of intestinally absorbed OCT was evaluated in normal rats and rats with portal hypertension (PH) that had been administered P-glycoprotein/multidrug resistance-associated protein 2/cytochrome P450 3A4 (P-gp/MRP2/CYP3A4) inhibitors. The mRNA and protein expression levels of P-gp, MRP2 and CYP3A4 were evaluated in normal and PH rats with or without OCT and the inhibitors using RT-PCR, western blot and immunohistochemical analyses. The potential effects of the inhibitor administration on PVP were also examined. The results suggest that P-gp, MRP2 and CYP3A4 play important roles in prohibiting the enteral absorption of OCT, particularly under a PH environment. Moreover, inhibitors of P-gp, MRP2 and CYP3A4 decrease the first-pass effects of OCT and effectively reduce PVP under PH conditions. Therefore, the present results suggest P-gp, MRP2 and CYP3A4 are key factors in the intestinal absorption of OCT. The inhibition of P-gp, MRP2 and CYP3A4 can markedly decrease the first-pass effects of OCT, and their use may facilitate the use of orally administered OCT.

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Section: Discussionmentioning

confidence: 99%

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Sun

Duan

Liu

et al. 2016

Experimental and Therapeutic Medicine

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“…Decreased hepatic levels of P-gp, MRP2, and CYP enzymes during the development of injuries such as Child’s class C cirrhosis or PBC III [ 12 – 14 ] have been reported. In general, drug dosages should be decreased in patients with severe cirrhosis [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of P-glycoprotein, MRP2, and CYP3A4 impairs intestinal absorption of octreotide in rats with portal hypertension

et al. 2021

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Background Portal hypertension (PH) is the main cause of complications and death in liver cirrhosis. The effect of oral administration of octreotide (OCT), a drug that reduces PH by the constriction of mesenteric arteries, is limited by a remarkable intestinal first-pass elimination. Methods The bile duct ligation (BDL) was used in rats to induce liver cirrhosis with PH to examine the kinetics and molecular factors such as P-glycoprotein (P-gp), multidrug resistance-associated protein 2 (MRP2) and cytochrome P450 3A4 (CYP3A4) influencing the intestinal OCT absorption via in situ and in vitro experiments on jejunal segments, transportation experiments on Caco-2 cells and experiments using intestinal microsomes and recombinant human CYP3A4. Moreover, RT-PCR, western blot, and immunohistochemistry were performed. Results Both in situ and in vitro experiments in jejunal segments showed that intestinal OCT absorption in both control and PH rats was largely controlled by P-gp and, to a lesser extent, by MRP2. OCT transport mediated by P-gp and MRP2 was demonstrated on Caco-2 cells. The results of RT-PCR, western blot, and immunohistochemistry suggested that impaired OCT absorption in PH was in part due to the jejunal upregulation of these two transporters. The use of intestinal microsomes and recombinant human CYP3A4 revealed that CYP3A4 metabolized OCT, and its upregulation in PH likely contributed to impaired drug absorption. Conclusions Inhibition of P-gp, MRP2, and CYP3A4 might represent a valid option for decreasing intestinal first-pass effects on orally administered OCT, thereby increasing its bioavailability to alleviate PH in patients with cirrhosis.

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“…Six human cytochrome P450 enzymes are known to be responsible for the final step generating the steroid hormone cortisol, which controls stress and glucose homeostasis (Brixius-Anderko and Scott, 2019). On the other hand, CYP3A4 enzymes are involved in eliminating steroid hormones (Wilkinson, 1996; Eldesoky et al , 2007). Cytochrome P450 oxidoreductase is responsible for the transfer of electrons from NADPH to all isoforms of microsomal cytochromes P450, including steroidogenic enzymes CYP17A1 (17α-hydroxylase/17,20-lyase), CYP19A1 (aromatase) and CYP21A2 (21-hydroxylase).…”

Section: Discussionmentioning

confidence: 99%

Chemiluminescence analysis of saliva for the assessment of emotional stress in autistic children undergoing a medical examination

Проскурнина

Portnova

Іванова

et al. 2021

AIA

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Purpose An electroencephalography (EEG) examination may cause psychological stress in children with autism that can interfere with the examination results. The objective information on the presence or absence of psycho-emotional stress in patients can help interpret electroencephalograms. This paper aimed to demonstrate the potential of noninvasive objective diagnostics of emotional stress in autistic children undergoing an EEG examination based on analysis of saliva. Design/methodology/approach This study involved 19 children with autism spectrum disorder (ASD) (ICD-10 F84.0); the mean age was seven years. During EEG examination of the children, behavioral parameters were assessed. The activity of cytochrome P450 reductase (CYPOR) in saliva was measured before and after the EEG procedure using lucigenin-enhanced nicotinamide adenine dinucleotide phosphate-stimulated chemiluminescence assay. Findings Significant differences in CYPOR activity were found between the children who were distressed during an EEG examination and the children without behavioral disturbances (Mann–Whitney test, p = 0.002). Thus, the EEG examination resulted in an increase in CYPOR activity in saliva cells, which may prove the stressful effect of this procedure on autistic children. Originality/value The chemiluminescent indices reflecting the activity of microsomal CYPOR in cells presenting in saliva correlate with the absence or presence of psychological stress in children; this phenomenon can be explained by an increased metabolism of the stress hormone, cortisol, by the cytochrome P450 microsomal system. Furthermore, the proposed method is completely safe, noninvasive, rapid (recording time is 20 min), inexpensive and promising for an objective assessment of psycho-emotional stress in autistic children undergoing medical examinations.

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Study of the Urinary Ratio of 6 β-Hydroxycortisol/Cortisol as a Biomarker of CYP3A4 Activity in Egyptian Patients with Chronic Liver Diseases

Cited by 4 publications

References 51 publications

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Inhibition of P-glycoprotein, multidrug resistance-associated protein 2 and cytochrome P450 3A4 improves the oral absorption of octreotide in rats with portal hypertension

Overexpression of P-glycoprotein, MRP2, and CYP3A4 impairs intestinal absorption of octreotide in rats with portal hypertension

Chemiluminescence analysis of saliva for the assessment of emotional stress in autistic children undergoing a medical examination

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