Article
Biochemistry & Molecular Biology
Jiahao Fang, Yuzhen He, Yuhong Cao, Yiwei Shi, Hui Wang, Zhanying Hong, Yifeng Chai
Summary: This study aimed to clarify the mechanism of four ingredients of S. miltiorrhiza in crossing the blood-brain barrier (BBB). The bidirectional transport of detectable components was tested using the MDCK-MDR1 monolayers, and HPLC-QQQ/MS was used to detect the content changes of S. miltiorrhiza monomer components transported through the BBB. The results showed that the transport of CTS, DTS I, and TS IIA might be related to P-gp, while the transport mechanism of PCTA and DTS I may be related to other transport proteins or passive transport.
ACS CHEMICAL NEUROSCIENCE
(2023)
Review
Chemistry, Multidisciplinary
Nazneen Pathan, Pravin Shende
Summary: P-Glycoprotein plays a vital role in the blood-brain barrier, protecting the central nervous system from infections and external toxic molecules. It is essential in various brain-related conditions but also poses a significant challenge in drug delivery across the blood-brain barrier.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Biochemistry & Molecular Biology
Vinicius Cavicchioli Azevedo, Christopher J. Kennedy
Summary: This study investigated the neuroprotective effects of inducing the blood-brain barrier protein P-gp with CTZ in zebrafish against the neurotoxicant IVM. The results showed that P-gp induction may have limited protective effects on the zebrafish CNS from IVM. Additionally, the effects of IVM and P-gp induction were not influenced by feeding or fasting.
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Yuheng Shan, Yuying Cen, Yanjin Zhang, Ruishu Tan, Jiahua Zhao, Zhiyong Nie, Jiatang Zhang, Shengyuan Yu
Summary: The study demonstrated that P-glycoprotein inhibition can enhance the brain concentration of ceftriaxone (CFX) and increase its penetration across the blood-brain barrier (BBB). Cyclosporin A increased both the brain concentration and the ratio of unbound brain to unbound blood concentration of CFX in a dose-dependent manner, while verapamil only increased the brain concentration of CFX without affecting the penetration ratio across the BBB. Future studies with more selective P-gp inhibitors or knockout mouse models are needed to further investigate the impact of P-gp inhibition on CFX penetration across the BBB.
NEUROCHEMICAL RESEARCH
(2022)
Article
Chemistry, Multidisciplinary
Severin Mairinger, Irene Hern, Thomas Filip, Michael Sauberer, Mathilde Lobsch, Johann Stanek, Thomas Wanek, Johannes A. Sake, Thomas Pekar, Carsten Ehrhardt, Oliver Langer
Summary: This study used positron emission tomography (PET) imaging to investigate the influence of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) on the pulmonary distribution of inhaled drugs. The results showed functional activity of P-gp and BCRP in the lungs and suggested that these transporters play a role in limiting the uptake of drugs in the lungs, similar to the blood-brain barrier. The study highlights the importance of pulmonary efflux transporters in the efficacy and safety of inhaled drugs.
JOURNAL OF CONTROLLED RELEASE
(2022)
Review
Multidisciplinary Sciences
Iman Imtiyaz Ahmed Juvale, Azzmer Azzar Abdul Hamid, Khairul Bariyyah Abd Halim, Ahmad Tarmizi Che Has
Summary: The multidrug resistance phenomenon poses a significant threat to the pharmaceutical industry and is mediated by multidrug transporters like P-glycoprotein. P-glycoprotein, with its versatile binding sites, accommodates various compounds and plays crucial roles in both multidrug resistant diseases and physiological functions in the human body.
Article
Chemistry, Multidisciplinary
Tong Wu, Yun Sheng, Yuan-yuan Qin, Wei-min Kong, Meng-meng Jin, Han-yu Yang, Xiao-ke Zheng, Chang Dai, Ming Liu, Xiao-dong Liu, Li Liu
Summary: This study demonstrated that liver failure affects the expression and function of brain BCRP and P-gp differently, attributed to the altered expression of membrane radixin and ezrin protein due to hyperbilirubinemia and hyperammonemia.
ACTA PHARMACOLOGICA SINICA
(2021)
Article
Geriatrics & Gerontology
Liangliang Huang, Yan Chen, Rui Liu, Binbin Li, Xuan Fei, Xiang Li, Ge Liu, Yunman Li, Baohui Xu, Weirong Fang
Summary: Increased expression of P-gp after ischemic injury leads to dysfunction and hyperpermeability of the BBB by suppressing Akt/mTOR-induced endothelial autophagy.
Article
Biochemistry & Molecular Biology
Vinicius C. Azevedo, Christopher J. Kennedy
Summary: This study examines the role of the blood-brain barrier ATP-binding cassette protein transporter P-glycoprotein (P-gp) in protecting zebrafish from the neurotoxic effects of the pesticide ivermectin. The results show that the presence of the competitive inhibitor cyclosporin A (CsA) increases the adverse effects of ivermectin on swimming and behavior in the fish. Additionally, fasting does not affect the protective role of P-gp against ivermectin. These findings suggest that P-gp plays a crucial role in defending fish from environmental neurotoxicants.
FISH PHYSIOLOGY AND BIOCHEMISTRY
(2022)
Article
Materials Science, Biomaterials
S. S. Priya, M. R. Rekha
Summary: Numerous reports have shown that the mutant p53 protein and P-glycoprotein overexpression have an inverse relationship, which negatively affects the sensitivity of cancer cells to chemotherapy. This study investigated the intracellular delivery of doxorubicin and the p53 gene using cationised pullulan polysaccharide conjugated with dithiobutyric acid (PPDBA), and examined the ability of PPDBA to modulate efflux pumps and retain drugs in different cell lines. The combination of PPDBA/p53 and low dose of DOX resulted in significantly higher cell death compared to DOX alone. In a mouse tumor model, the PPDBA II/p53/DOX nanoplexes showed promising efficacy.
JOURNAL OF MATERIALS CHEMISTRY B
(2023)
Article
Pharmacology & Pharmacy
Jae Pyun, Huijing Koay, Pranav Runwal, Celeste Mawal, Ashley I. Bush, Yijun Pan, Paul S. Donnelly, Jennifer L. Short, Joseph A. Nicolazzo
Summary: Cu(ATSM) enhances the expression and function of P-gp at the blood-brain barrier, which has important implications for CNS drug delivery and clearance of A beta in AD.
Article
Toxicology
Laurens F. M. Verscheijden, Jan B. Koenderink, Saskia N. de Wildt, Frans G. M. Russel
Summary: The study found that BBB Pgp activity is species-specific, and an age-dependent PBPK model can optimize predictions of brain drug concentrations. The methods used in the study have the potential to address challenges in extrapolating brain drug disposition and toxicity.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Chemistry, Medicinal
Na Li, Priyanka Kulkarni, Akshay Badrinarayanan, Adey Kefelegn, Raffi Manoukian, Xingwen Li, Bhagwat Prasad, Matthew Karasu, William J. McCarty, Charles G. Knutson, Anshul Gupta
Summary: This study found that the level of P-gp expression plays a critical role in efflux assay, with cell lines expressing higher levels of P-gp being more accurate in predicting brain penetration of drugs. Conversely, lower P-gp expression in cell lines may result in false negative results in efflux assays.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Amanda B. Chai, Richard Callaghan, Ingrid C. Gelissen
Summary: This review summarizes the current understanding of P-gp regulation in the brain, including transcriptional, post-transcriptional, and post-translational mechanisms, aiming to provide new strategies for optimizing therapeutic outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Ryuta Jomura, Shin-ichi Akanuma, Bjorn Bauer, Yukiko Yoshida, Yoshiyuki Kubo, Ken-ichi Hosoya
Summary: The study investigated the transport of phenytoin across the blood-brain barrier (BBB), identifying that MCT8 participates in the efflux of phenytoin from the brain to the blood. Meanwhile, P-gp did not affect the efflux of phenytoin from the brain.
PHARMACEUTICAL RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Oliver Bruhn, Marie Lindsay, Friederike Wiebel, Meike Kaehler, Inga Nagel, Ruwen Boehm, Christian Roeder, Ingolf Cascorbi
MOLECULAR PHARMACOLOGY
(2020)
Article
Anesthesiology
Juliane Sachau, Henrike Bruckmueller, Janne Gierthmuehlen, Walter Magerl, Denisa May, Andreas Binder, Julia Forstenpointner, Judith Koetting, Christoph Maier, Thomas R. Toelle, Rolf-Detlef Treede, Achim Berthele, Amke Caliebe, Carolin Diesch, Herta Flor, Volker Huge, Christian Maihoefner, Stefanie Rehm, Dilara Kersebaum, Sophie-Charlotte Fabig, Jan Vollert, Roman Rolke, Susanne Stemmler, Claudia Sommer, Andrea Westermann, Ingolf Cascorbi, Ralf Baron
Summary: The study revealed an association of the HTR2A gene variant rs6313 with pinprick hyperalgesia and increased levels of ongoing pain in neuropathic pain patients with sensory loss. This suggests that the HTR2A receptor may play a crucial role in the development of central sensitization in neuropathic pain.
EUROPEAN JOURNAL OF PAIN
(2021)
Review
Biochemistry & Molecular Biology
Henrike Bruckmueller, Ingolf Cascorbi
Summary: Despite significant efforts, studies on genetic variants in ABC efflux transporters have shown weak associations with drug pharmacokinetics and response. Majority of studies have failed to confirm earlier findings and remain inconsistent. The impact of genetic variants on drug bioavailability is minor, with other factors regulating transporter expression and function being more critical. Overall, these genetic variants are not suitable as predictive biomarkers.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2021)
Review
Medicine, General & Internal
Anna Katharina Seoudy, Dominik M. Schulte, Tim Hollstein, Ruwen Boehm, Ingolf Cascorbi, Matthias Laudes
Summary: SGLT2 inhibitors have shown efficacy in treating type 2 diabetes, as well as congestive heart failure and renal failure. Recent studies have demonstrated their favorable effects on multiple renal endpoints, making them a significant class of drugs for the treatment of HFrEF and renal failure, regardless of the presence of type 2 diabetes.
DEUTSCHES ARZTEBLATT INTERNATIONAL
(2021)
Article
Pharmacology & Pharmacy
Ruwen Boehm, Claudia Bulin, Vicki Waetzig, Ingolf Cascorbi, Hans-Joachim Klein, Thomas Herdegen
Summary: Pharmacovigilance data is primarily used to identify adverse drug reactions, but scanning for associations of drugs and adverse events that occur less frequently than expected can provide hypotheses for drug repurposing. This study extracted drugs associated with viral respiratory tract infections and RNA-virus diseases similar to SARS-CoV-2 from US FAERS data, identifying potential antiviral candidates for further exploration. The study suggests that scanning for inverse signals in pharmacovigilance data can lead to new hypotheses for drug repurposing across multiple indications.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2021)
Article
Anesthesiology
Ruwen Bohm, Paul Westermann, Martin Gleim, Ingolf Cascorbi, Matthias Gruenewald, Thomas Herdegen, Henning Ohnesorge
Summary: This study demonstrated that spironolactone at a dose of 200 mg/day did not improve symptoms in women with fibromyalgia syndrome (FMS), but also did not cause harm. Spironolactone led to transient side effects including a rise in serum potassium and a decrease in GFR, which were not clinically significant.
EUROPEAN JOURNAL OF PAIN
(2021)
Article
Medicine, Research & Experimental
Charles Awortwe, Henrike Bruckmueller, Meike Kaehler, Ingolf Cascorbi
Summary: The study investigated the effects of Echinacea purpurea compounds on the expression and transport activity of ABCB1 and ABCG2 proteins, showing heterogeneous induction by the compounds but no significant inhibition of transporter activity was found.
MOLECULAR PHARMACEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Jan Kneusels, Meike Kaehler, Ingolf Cascorbi, Thilo Wedel, Michel Neunlist, Ralph Lucius, Francois Cossais
Summary: Increasing evidence suggests that the enteric nervous system (ENS) and enteric glial cells (EGC) play significant roles in intestinal inflammation. The cytostatic compound mercaptopurine (6-MP) used for treating inflammatory bowel diseases may have anti-inflammatory effects on ENS response to inflammation, which requires further investigation to uncover the cellular mechanisms involved.
NEUROCHEMICAL RESEARCH
(2021)
Editorial Material
Pharmacology & Pharmacy
Ingolf Cascorbi
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Hematology
Meike Kaehler, Maike Dworschak, Julian Phillip Rodin, Johanna Ruemenapp, Inga Vater, Eva Maria Murga Penas, Catherine Liu, Ingolf Cascorbi, Inga Nagel
Summary: ZFP36L1 and ZFP36L2 play roles in CML, with their expression dysregulation in patients and increased expression during resistance development to tyrosine kinase inhibitors. Knockout of ZFP36L1 using CRISPR/Cas9 showed potential as a tumor suppressor gene.
EXPERIMENTAL HEMATOLOGY
(2021)
Meeting Abstract
Pharmacology & Pharmacy
M. Litterst, I. Nagel, I. Cascorbi, M. Kaehler
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Meeting Abstract
Pharmacology & Pharmacy
V. Tenhaken, J. Bruckmueller, B. Anangi, B. Johansen, H. Kildalsen, J. Mejlvang, I. Nagel, I. Cascorbi, O. M. Seternes, H. Bruckmueller
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Meeting Abstract
Pharmacology & Pharmacy
R. Boehm, C. Bulin, V. Waetzig, I. Cascorbi, H. J. Klein, T. Herdegen
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Meeting Abstract
Pharmacology & Pharmacy
M. Dworschak, M. Kaehler, I. Cascorbi, I. Nagel
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2021)
Article
Medicine, General & Internal
Ibrahim Alkatout, Veronika Guenther, Sandra Bruegge, Johannes Ackermann, Magret Krueger, Dirk Bauerschlag, Nicolai Maass, Sebastian Lippross, Ingolf Cascorbi, Jan-Hendrik Egberts, Thomas Becker, Daniar Osmonov, Klaus-Peter Juenemann, Thilo Wedel
Summary: Participation in scientific congresses during early medical education positively impacts students' learning motivation and interest in surgical careers, making it a valuable supplement to the educational curriculum.
WIENER MEDIZINISCHE WOCHENSCHRIFT
(2021)