The In Vivo Effects of Adenine-Induced Chronic Kidney Disease on Some Renal and Hepatic Function and CYP450 Metabolizing Enzymes

Za’abi, Mohammed Al; Shalaby, Al Shimaa Gamal; Manoj, P; Ali, Badreldin H.

doi:10.33549/physiolres.933374

Cited by 10 publications

(6 citation statements)

References 34 publications

(19 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, a recent study investigated the effects of adenine-induced chronic kidney disease (CKD) in rats on the activities of some XMEs in liver and kidneys. It was found that the plasma theophylline concentration was significantly increased in rats with CKD 206 . Moreover, a reduced metabolism of midazolam could be observed in rats with acute kidney injury (AKI) 207 .…”

Section: Disease–drug Interactionsmentioning

confidence: 99%

“…Among them, the effects of polymicrobial sepsis on the activity and gene expression of hepatic microsomal CYP450 have attracted considerable attention due to their potential disease–drug interactions in clinical therapy. It has been reported that the major hepatic CYP isoforms CYP1A1, 1A2, 2B1, 2E1 were down-regulated during polymicrobial sepsis 208 , 203, 204, 205, 206, 207, 208, 209, 210, 211, 212, 213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224. Moreover, results from mechanistic studies show that nitric oxide (NO) and the AhR play key potential roles in down-regulation of hepatic CYP during sepsis 225 , 226 .…”

Section: Disease–drug Interactionsmentioning

confidence: 99%

See 1 more Smart Citation

Current trends in drug metabolism and pharmacokinetics

Meng

Yang

et al. 2019

Acta Pharmaceutica Sinica B

190

124

View full text Add to dashboard Cite

Pharmacokinetics (PK) is the study of the absorption, distribution, metabolism, and excretion (ADME) processes of a drug. Understanding PK properties is essential for drug development and precision medication. In this review we provided an overview of recent research on PK with focus on the following aspects: (1) an update on drug-metabolizing enzymes and transporters in the determination of PK, as well as advances in xenobiotic receptors and noncoding RNAs (ncRNAs) in the modulation of PK, providing new understanding of the transcriptional and posttranscriptional regulatory mechanisms that result in inter-individual variations in pharmacotherapy; (2) current status and trends in assessing drug–drug interactions, especially interactions between drugs and herbs, between drugs and therapeutic biologics, and microbiota-mediated interactions; (3) advances in understanding the effects of diseases on PK, particularly changes in metabolizing enzymes and transporters with disease progression; (4) trends in mathematical modeling including physiologically-based PK modeling and novel animal models such as CRISPR/Cas9-based animal models for DMPK studies; (5) emerging non-classical xenobiotic metabolic pathways and the involvement of novel metabolic enzymes, especially non-P450s. Existing challenges and perspectives on future directions are discussed, and may stimulate the development of new research models, technologies, and strategies towards the development of better drugs and improved clinical practice.

show abstract

Section: Disease–drug Interactionsmentioning

confidence: 99%

Section: Disease–drug Interactionsmentioning

confidence: 99%

Current trends in drug metabolism and pharmacokinetics

Meng

Yang

et al. 2019

Acta Pharmaceutica Sinica B

190

124

View full text Add to dashboard Cite

show abstract

“…Our results support findings from other studies showing a lack of adenine hepatotoxicity ( 42 , 43 ). However, another study reported a hepatotoxic effect of adenine as demonstrated by elevated liver enzymes in response to inflammation ( 44 ). This is in contrast with the results of our study, in which increased systemic inflammation was not associated with elevated liver enzymes in adenine-treated animals.…”

Section: Discussionmentioning

confidence: 99%

Paradoxical reduction of plasma lipids and atherosclerosis in mice with adenine-induced chronic kidney disease and hypercholesterolemia

Padalkar

Tsivitis²,

Gelfman³

et al. 2023

Front. Cardiovasc. Med.

View full text Add to dashboard Cite

BackgroundAtherosclerotic cardiovascular disease is prevalent among patients with chronic kidney disease (CKD). In this study, we initially aimed to test whether vascular calcification associated with CKD can worsen atherosclerosis. However, a paradoxical finding emerged from attempting to test this hypothesis in a mouse model of adenine-induced CKD.MethodsWe combined adenine-induced CKD and diet-induced atherosclerosis in mice with a mutation in the low-density lipoprotein receptor gene. In the first study, mice were co-treated with 0.2% adenine in a western diet for 8 weeks to induce CKD and atherosclerosis simultaneously. In the second study, mice were pre-treated with adenine in a regular diet for 8 weeks, followed by a western diet for another 8 weeks.ResultsCo-treatment with adenine and a western diet resulted in a reduction of plasma triglycerides and cholesterol, liver lipid contents, and atherosclerosis in co-treated mice when compared with the western-only group, despite a fully penetrant CKD phenotype developed in response to adenine. In the two-step model, renal tubulointerstitial damage and polyuria persisted after the discontinuation of adenine in the adenine-pre-treated mice. The mice, however, had similar plasma triglycerides, cholesterol, liver lipid contents, and aortic root atherosclerosis after being fed a western diet, irrespective of adenine pre-treatment. Unexpectedly, adenine pre-treated mice consumed twice the calories from the diet as those not pre-treated without showing an increase in body weight.ConclusionThe adenine-induced CKD model does not recapitulate accelerated atherosclerosis, limiting its use in pre-clinical studies. The results indicate that excessive adenine intake impacts lipid metabolism.

show abstract

“…CYP2S1 was recently discovered, and it is expressed in the skin and the small intestines. This enzyme is involved in all-transretinoic acid metabolism into the skin [141,142]. There is no information about its expression in patients with CKD.…”

Section: Alterations Of Drug Metabolism During Chronic Kidney Diseasementioning

confidence: 99%

Emerging Roles of Aryl Hydrocarbon Receptors in the Altered Clearance of Drugs during Chronic Kidney Disease

Machado

Cérini

Burtey

2019

Toxins

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is a major public health problem, since 300,000,000 people in the world display a glomerular filtration rate (GFR) below 60 mL/min/1.73m2. Patients with CKD have high rates of complications and comorbidities. Thus, they require the prescription of numerous medications, making the management of patients very complex. The prescription of numerous drugs associated with an altered renal- and non-renal clearance makes dose adjustment challenging in these patients, with frequent drug-related adverse events. However, the mechanisms involved in this abnormal drug clearance during CKD are not still well identified. We propose here that the transcription factor, aryl hydrocarbon receptor, which is the cellular receptor for indolic uremic toxins, could worsen the metabolism and the excretion of drugs in CKD patients.

show abstract

The In Vivo Effects of Adenine-Induced Chronic Kidney Disease on Some Renal and Hepatic Function and CYP450 Metabolizing Enzymes

Cited by 10 publications

References 34 publications

Current trends in drug metabolism and pharmacokinetics

Current trends in drug metabolism and pharmacokinetics

Paradoxical reduction of plasma lipids and atherosclerosis in mice with adenine-induced chronic kidney disease and hypercholesterolemia

Emerging Roles of Aryl Hydrocarbon Receptors in the Altered Clearance of Drugs during Chronic Kidney Disease

Contact Info

Product

Resources

About