Current drug metabolism最新文献

{"title":"In vitro and In vivo Drug Metabolism Analysis of BPI-460372 - A Covalent TEAD1/3/4 Inhibitor.","authors":"Xiaoyun Liu, Dafang Zhong, Chong Zhuang Tang, Xiaofeng Xu, Hong Lan, Xingxing Diao","doi":"10.2174/0113892002351556250123105344","DOIUrl":"https://doi.org/10.2174/0113892002351556250123105344","url":null,"abstract":"<p><strong>Background: </strong>BPI-460372 is an orally available, covalent, irreversible small molecule inhibitor of the transcriptional enhanced associate domain (TEAD) 1/3/4, which is currently in clinical development for the treatment of cancers with Hippo pathway alterations.</p><p><strong>Objective: </strong>This study aimed to determine the cytochrome P450 (CYP) phenotyping, metabolic stability, and in vitro and in vivo metabolic profile of BPI-460372.</p><p><strong>Methods: </strong>The CYP phenotyping and metabolic stability were assessed by measuring the depletion of substrate. The metabolic profile in hepatocytes and rat and dog plasma was analyzed using ultra-high-performance liquid chromatography combined with Orbitrap tandem mass spectrometry (UHPLC-Orbitrap-HRMS).</p><p><strong>Results: </strong>BPI-460372 was mainly metabolized by CYP2D6, CYP3A4, and CYP1A2. BPI-460372 exhibited low clearance in human, monkey, and rat hepatocytes, while moderate clearance in dog and mouse hepatocytes. A total of 10 metabolites were identified in five species of hepatocytes, and no human-unique metabolite was detected. In rat plasma and dog plasma, the primary metabolites were M407 (BPI-460430) and M423 (BPI-460456), respectively. The two metabolites were quantitatively determined in rat and dog plasma in pharmacokinetic and toxicological studies. The major metabolic site was 2-fluoro-acrylamide, and major metabolic pathways in hepatocytes, and rat and dog plasma involved oxidative defluorination, hydration, glutathione (GSH) conjugation, hydrolysis, cysteine conjugation, and N-acetyl cysteine conjugation. β-lyase pathway contributed to the metabolism of BPI-460372 in rats to a certain degree.</p><p><strong>Conclusion: </strong>This study elucidated the metabolism of BPI-460372 and provided a basis for pharmacokinetic and toxicological species selection, human pharmacokinetics prediction, and assessment of clinical co-administration limitations and possible metabolic pathways in humans.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review on Drug-Metabolizing Enzymes, Transporters, and Gut Microbiota on Pharmacokinetics in High-Altitude Environment.","authors":"Fangfang Qiu, Yuemei Sun, Wenbin Li, Rong Wang","doi":"10.2174/0113892002356402250130075811","DOIUrl":"https://doi.org/10.2174/0113892002356402250130075811","url":null,"abstract":"<p><p>The most significant feature of the high-altitude environment is hypoxia, which affects the activity and expression of drug-metabolizing enzymes and transporters, leading to changes in pharmacokinetic parameters. Notably, gut microbiota is a hidden organ in the body. High-altitude hypoxia will change the composition and quantity of gut microbiota, affect drug metabolism, and change the bioavailability of drugs. This will provide a new perspective on changes in pharmacokinetics at high-altitude. Most studies have revealed that for drugs with low bioavailability and high clearance, the dosage may be increased accordingly. Conversely, the dosage may be reduced to achieve individualized medication. Therefore, this article reviews the changes and mechanisms of drug-metabolizing enzymes, transporters, and gut microbiota in a high-altitude environment and explains the impact of their changes on pharmacokinetics, aiming to provide theories and bases for the adjustment of drug dosage and the rational use of drugs in the clinic under high-altitude environment.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Umbelliferone Enhances Immune Function in Cyclophosphamide-Induced Immunosuppressed Mice via Histidine and Purine Metabolism Regulation.","authors":"Mei Li, Jing Wang, Bingjie Huo, Qianqian Wan, Liwei Xing, Yuming Wang, Huan Pei, Li Wang, Yafei Xia, Huantian Cui","doi":"10.2174/0113892002360132250122164637","DOIUrl":"https://doi.org/10.2174/0113892002360132250122164637","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy-induced immunosuppression significantly impacts patient's quality of life. Umbelliferone (UMB) is known for its anti-inflammatory, antioxidant, and anti-apoptotic properties, but its effects on cyclophosphamide (CTX)-induced immunosuppression need further study.</p><p><strong>Methods: </strong>We established a CTX-induced immunosuppressed mouse model and administered varying doses of UMB. Immune function was assessed by evaluating white blood cells, lymphocytes, thymus and spleen indices, and CD4+/CD8+ T cell ratios. Serum levels of IL-2, IFN-γ, IgA, IgM, and IgG, along with macrophage phagocytic activity, NK cytotoxicity, and lymphocyte proliferation, were measured. Untargeted metabolomics was used to identify key pathways regulated by UMB, and RT-qPCR and Western blotting were performed to analyze the expression of related enzymes and metabolites.</p><p><strong>Results: </strong>UMB intervention increased white blood cells, lymphocytes, thymus and spleen indices, and CD4+/CD8+ T cell ratios in CTX-immunosuppressed mice. It reversed reduced levels of serum IL-2, IFN-γ, IgA, IgM, and IgG and improved macrophage phagocytic activity, NK cytotoxicity, and lymphocyte proliferation. Key pathways identified by metabolomics included histidine and purine metabolism. UMB improved levels of histamine, L-glutamate, L-aspartate, xanthine, dAMP, deoxyinosine, xanthosine, and cGMP and upregulated HDC, ASPA, and PNP while downregulating XDH, PDE5, ROS, and MDA in spleen tissue. UMB enhanced SOD activity and GSH levels and reduced apoptosis, as indicated by lower TUNEL-positive expression.</p><p><strong>Conclusion: </strong>UMB enhanced immune function in CTX-immunosuppressed mice through the regulation of histidine and purine metabolism, exhibiting antioxidant and anti-apoptotic effects. These findings highlight the potential of UMB in mitigating immunosuppression.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Alteration of Rifampicin's Bioavailability by Phyllanthus niruri Supplementation in Tuberculosis Therapy.","authors":"Mirhansyah Ardana, Marlyn Dian Laksitorini, Endang Lukitaningsih, Agung Endro Nugroho","doi":"10.2174/0113892002361205250123101231","DOIUrl":"https://doi.org/10.2174/0113892002361205250123101231","url":null,"abstract":"<p><p>Rifampicin is essential for treating TB. The high incidence of resistance to this drug requires efforts to increase the effectiveness of TB therapy. Immunomodulator supplementation is one effort to overcome this problem. Phyllanthus niruri has an immunomodulating effect, which has been proven to influence the clinical improvement of the immunological profile. However, the effect of this plant on rifampicin's bioavailability should be reviewed to determine potential changes that may affect its antibacterial performance. Several stud-ies have shown an increase in the bioavailability of rifampicin when administered with extracts and active isolates of Carum carvi, Cuminum cyminum, Piper nigrum, and Moringa oleifera through inhibition of the P-gp efflux function in the absorption phase. On the other hand, the decrease occurred in coadministration with Garcinia cola, which activated PXR action and subsequently changed P-gp regulation. Administration of Al-lium sativum and Zingiber officinale extracts did not show significant alteration in bioavailability due to the stimulation of several mechanisms with opposite outputs by each secondary metabolite. In the case of P. niruri supplementation, the potential for a rise in bioavailability could occur due to synergistic effects inhibiting the performance of P-gp, AADAC, and OATP1B. However, the stimulation of PXR and PPARα may reduce or eliminate these effects. Finally, considering that there are so many specific secondary metabolites in P. niruri whose effects on the performance of these functional proteins have not been exposed, in vivo studies are needed to confirm the interactions within complex biological systems.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Interactions of Paxlovid Involving CYP3A Enzymes and P-gp Transporter: An Overview of Clinical Data.","authors":"Naina Mohamed Pakkir Maideen, Krishnaveni Kandasamy, Rajkapoor Balasubramanian","doi":"10.2174/0113892002320326250123082112","DOIUrl":"https://doi.org/10.2174/0113892002320326250123082112","url":null,"abstract":"<p><strong>Background: </strong>The US FDA has approved paxlovid, a combination of nirmatrelvir and ritonavir, as the first oral treatment for the management of mild-to-moderate COVID-19 patients.</p><p><strong>Objective: </strong>The purpose of this review article is to explore the clinical data that is currently available regarding the drug-drug interactions (DDIs) of paxlovid with various medications.</p><p><strong>Methods: </strong>Keywords, such as drug interactions, paxlovid, ritonavir, nirmatrelvir, pharmacokinetic interactions, CYP3A, and P-glycoprotein, were used to search online databases, including LitCOVID, Scopus, Embase, EBSCO host, Google Scholar, ScienceDirect, Cochrane Library, and reference lists.</p><p><strong>Results: </strong>Paxlovid interacted with a variety of medications due to strong inhibition of CYP3A4 and P-gp transporter protein by ritonavir and the dual function of nirmatrelvir as a substrate and inhibitor of CYP3A enzymes and P-gp transporter protein. Numerous case reports and other studies determined that the risk of toxicities of several drugs, including anticoagulants (warfarin, rivaroxaban), calcium channel blockers (nifedipine, manidipine, verapamil), statins (atorvastatin), immunosuppressants (tacrolimus), antiarrhythmics (amiodarone), antipsychotics (clozapine, quetiapine), and ranolazine have been enhanced by the concomitant administration of paxlovid.</p><p><strong>Conclusion: </strong>Adverse effects of paxlovid from DDIs can range from less-than-ideal therapeutic responses to potentially fatal toxicities. Effective management requires close observation, adjustments to dosage, and assessment of substitute treatments. Collaboration between pharmacists and other medical professionals is necessary to guarantee effective and safe treatment outcomes of paxlovid therapy.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Shenmai Injection on the Pharmacokinetics of Dasatinib: An In-Depth In vivo Analysis Utilizing UPLC-MS/MS Technique.","authors":"Weina Ma, Ling Li, Zhihui Li, Jungang Guo, Yifei Zhu, Liye Ge, Rong Wang, Lei Lv","doi":"10.2174/0113892002336775250108112738","DOIUrl":"https://doi.org/10.2174/0113892002336775250108112738","url":null,"abstract":"<p><strong>Background: </strong>Dasatinib has been widely used in the treatment of a variety of cancers, such as lung cancer and acute myeloid leukemia. Shenmai injection is a traditional Chinese medicine injection that is often used in antitumor adjuvant therapy. In recent years, dasatinib combined with Shenmai injection has been increasingly used to treat tumors clinically. However, the potential risks and benefits of co-administering Shenmai injection and dasatinib are unclear.</p><p><strong>Objective: </strong>The study aimed to investigate the potential influence of Shenmai injection on dasatinib pharmacokinetics.</p><p><strong>Methods: </strong>Twelve rats were selected and randomly divided into two groups: dasatinib alone and a combination of dasatinib and Shenmai injection. To measure the concentration of dasatinib in rat plasma, blood samples were obtained from the orbital vein. Using ultra-performance liquid chromatography-tandem mass spectrometry, the concentration of dasatinib was determined to obtain pharmacokinetic parameters.</p><p><strong>Results: </strong>Compared to the dasatinib alone administration, the maximum concentration of the dasatinib plus Shenmai injection administration was decreased (355.9 ± 194.9 vs. 199.2 ± 73.8 ng·mL-1) (P < 0.05). Moreover, the area under the moment curve (3867.0 ± 2141.9 vs. 6355.3 ± 3311.6 ng·mL-1·h2) and mean residence time (3.7 ± 1.2 vs. 6.5 ± 3.1 h) showed a statistically significant increase (P < 0.05).</p><p><strong>Conclusion: </strong>The study revealed that Shenmai injection might have the capacity to slow down the absorption rate of dasatinib and could extend the retention period of dasatinib in the body, resulting in stabilized blood drug concentrations and a reduction in adverse drug reactions.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hallmarks of Quercetin Benefits as a Functional Supplementary in the Management of Diabetes Mellitus-Related Maladies: From Basic to Clinical Applications.","authors":"Faegheh Farhadi, Fariba Sharififar, Mandana Jafari, Vafa Baradaran Rahimi, Nafiseh Askari, Vahid Reza Askari","doi":"10.2174/0113892002339410250108031621","DOIUrl":"https://doi.org/10.2174/0113892002339410250108031621","url":null,"abstract":"<p><p>Quercetin (QE), a particular flavonoid, is well known for its medicinal effects, including anti-oxidant, hypoglycemic, and anti-inflammatory effects. In this review, the findings of QE effects on diabetes STZinduced, alloxan-induced, and its complications have been summarized with a particular focus on in vitro, in vivo, and clinical trials. Consequently, QE mediates several mechanisms, including ameliorating tumor necrosis factor (TNF)-α, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin (IL)-1β, IL-8, and IL-10 expression, increasing insulin glucose uptake to inhibit insulin resistance. Moreover, QE stimulates insulin secretion and attenuates insulin resistance through various pathways, namely transient KATP channel, motivating peroxisome proliferator-activated receptor expression, increasing glucose transporter-4, and decreasing inducible nitric oxide synthase in skeletal muscle. QE has protective effects on the complications caused by diabetes, such as polycystic ovary syndrome, high-fat diet-induced obesity, diabetic-induced hepatic damage, vascular inflammation, nephropathy, and neuropathy.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Drug-Drug Interactions between Losartan and Carbamazepine: A Pharmacokinetic and Pharmacodynamic Study.","authors":"Shruthi A Sundargowda, Sunil Kumar Kadiri","doi":"10.2174/0113892002358068250119052940","DOIUrl":"https://doi.org/10.2174/0113892002358068250119052940","url":null,"abstract":"<p><strong>Background: </strong>Hypertension, which affects 1.28 billion people globally aged 30 to 79, is characterized by continuously high blood pressure (140/90 or more) and raises the risk of premature death. Losartan, an angiotensin receptor blocker (ARB), is suggested for patients under the age of 55 who cannot take ACE inhibitors as a first treatment option. Epilepsy, a chronic neurological illness marked by repeated seizures, affects more than 50 million individuals worldwide and is the third most common chronic brain disorder. Both hypertension and epilepsy are frequent chronic illnesses, with increased blood pressure greatly raising the risk of epilepsy due to its relationship with cerebrovascular disease, doubling the risk when compared to people with normal blood pressure.</p><p><strong>Objective: </strong>The effect on pharmacokinetic and pharmacodynamics of losartan on concomitant administration with carbamazepine was investigated.</p><p><strong>Materials and methods: </strong>Wistar rats of either sex, with a minimum of six animals per group, were used in the investigation. The rats were treated with Losartan and Losartan-Carbamazepine for 30 days. Blood samples were taken via retro-orbital plexus at 0, 1, 2, 4, 6, and 12 hours after treatment concluded, and they were subjected to high-performance liquid chromatography for plasma analysis to calculate AUC, t1/2, and Clearance. A pharmacodynamic evaluation was done by inducing hypertension in rats using a 10% fructose solution and the effect of pretreated Losartan and Losartan-Carbamazepine on blood pressure was determined.</p><p><strong>Results: </strong>In the Losartan and Carbamazepine treated group, there was a reduction in the AUC and t1/2 and a reported increase in the clearance value compared to Losartan alone treated rats. In fructose-induced hypertension model to evaluate the effect of losartan and carbamazepine on BP showed an increase in mean arterial pressure, plasma glucose, and a reduction in triglycerides level was noted in comparison to Losartan alone treated rats indicating therapeutic failure of Losartan.</p><p><strong>Conclusion: </strong>Based on these studies, it is concluded that CBZ has reduced the effectiveness of losartan and therefore, co-administration of these drugs should be avoided.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of Five Natural Anthraquinone Compounds as Potent Inhibitors against CYP1B1: Implications for Cancer Treatment.","authors":"Zujia Chen, Zhixiang Xu, Xiaodong Chen, Xintong Guan, Jie Du, Jia Hui Zhang, Chang Yuan Wang, Jingjing Wu","doi":"10.2174/0113892002329282250108163208","DOIUrl":"https://doi.org/10.2174/0113892002329282250108163208","url":null,"abstract":"<p><strong>Background: </strong>Human cytochrome P450 1B1 (CYP1B1) is an extrahepatic enzyme that is overexpressed in many tumors and is associated with tumor development and acquired resistance. Few studies have reported that anthraquinone compounds have inhibitory activity against the CYP1B1 enzyme. Cassiae semen (Leguminosae) is a well-known traditional Chinese medicine containing more than 70 compounds. The crude extracts and pure compounds of Cassiae semen have been widely used in preclinical and clinical practice for their beneficial effects, such as neuroprotective, hepatoprotective, antimicrobial, antioxidant, and hypotensive effects. Aloe-emodin, chrysophanol, obtusifolin, aurantio-obtusin, and rhein are important active natural anthraquinones in Cassiae semen.</p><p><strong>Objective: </strong>Aloe-emodin, chrysophanol, obtusifolin, aurantio-obtusin, and rhein have a wide range of pharmacological activities and have been found to have good anti-tumor and antioxidant effects. However, the underlying mechanisms of these pharmacological activities remain poorly understood. This study aimed to investigate the inhibitory effects of five natural anthraquinones on the activity of CYP1B1 and to analyze the structure- activity relationship of these compounds.</p><p><strong>Materials and methods: </strong>In this study, 7-ethoxyresorufin O-deethylation (EROD) was used as the fluorescent substrate of CYP1B1 to investigate the inhibition effect, and molecular docking was performed to further determine the structural-activity relationship of the compound molecules.</p><p><strong>Results: </strong>We found that aloe-emodin and chrysophanol had strong inhibitory effects on CYP1B1 with IC50 values of 0.28 and 0.34μM, respectively, while obtusifolin and aurantio-obtusin had IC50 values of 0.77μM and 9.11μM, respectively. The structural activity analysis showed that the inhibition strength was related to the position of the hydroxyl group substitution and the number of methoxy group substitutions. Rhein containing one carboxyl group showed the weakest inhibition of 23.72μM. The inhibition kinetics showed that all five compounds belonged to the non-competitive inhibition model. The inhibition kinetics revealed that all five compounds exhibited the non-competitive inhibition model.</p><p><strong>Conclusion: </strong>The present study provided a comprehensive analysis of the inhibitory effects of five natural anthraquinones, namely aloe-emodin, chrysophanol, obtusifolin, aurantio-obtusin and rhein, on CYP1B1 activity, and elucidated the structure-activity relationship. Molecular docking simulations further revealed the specific amino acid residues within the active site of CYP1B1, where these compounds exerted their actions. These findings offer novel insights into investigating the potential antitumor properties of natural anthraquinones.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Interplay: Antioxidant Enzyme Polymorphisms and Oxidative Stress in Preterm Neonatal Renal and Hepatic Functions.","authors":"Kannan Sridharan, Mona Al Jufairi","doi":"10.2174/0113892002328584240923095216","DOIUrl":"10.2174/0113892002328584240923095216","url":null,"abstract":"<p><strong>Aims: </strong>To explore the relationship between oxidative stress biomarkers and the occurrence of acute kidney injury (AKI) alongside notable liver function disturbances in preterm neonates.</p><p><strong>Background: </strong>Given the immaturity of kidneys and incomplete liver development in preterm neonates, oxidative stress poses a considerable threat to their renal and hepatic health.</p><p><strong>Objective: </strong>To find out the association between various oxidative stress biomarkers and polymorphisms of antioxidant enzymes with renal and live functions.</p><p><strong>Methods: </strong>In this cross-sectional study, we gathered umbilical cord blood and peripheral blood samples for assessing oxidative stress biomarkers and identifying single nucleotide polymorphisms (SNPs) in antioxidant enzymes. Utilizing enzyme-linked immunosorbent assay kits, we quantified these oxidative stress biomarkers. Receiver-operating characteristics curve analysis was employed to ascertain the predictive capacity of these biomarkers, denoted by the area-under-the-curve (AUC).</p><p><strong>Results: </strong>Our findings revealed that umbilical cord heat-shock proteins emerged as robust predictors of neonatal AKI (AUC: 0.92; 95% CI: 0.8-1) with a defined cut-off concentration of 1.8 ng/mL. Likewise, umbilical cord 8-hydroxy-2-deoxy guanosine demonstrated significant predictability for liver function alterations (AUC: 0.7; 95% CI: 0.6-0.9) at a cut-off concentration of 2487.6 pg/mL.</p><p><strong>Conclusions: </strong>We observed significant associations between SNPs in endothelial nitric oxide synthase and catalase with both AKI and impaired liver functions. Prospective studies are warranted to validate these findings, with a particular focus on exploring potential antioxidant interventions aimed at mitigating AKI and liver function abnormalities.</p>","PeriodicalId":10770,"journal":{"name":"Current drug metabolism","volume":" ","pages":"605-612"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}