Statins: Complex outcomes but increasingly helpful treatment options for patients

Mohammadkhani, Niloufar; Gharbi, Sedigheh; Rajani, Huda Fatima; Farzaneh, Avishan; Mahjoob, Golnoosh; Hoseinsalari, Afsaneh; Korsching, Eberhard

doi:10.1016/j.ejphar.2019.172704

Cited by 26 publications

(16 citation statements)

References 95 publications

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“…Recently, an increased number of studies have investigated via in vitro and in vivo experiments various combinatorial chemotherapy regimens with compounds from different classes, i.e., statins, curcuminoids, or isothiocyanate [20][21][22], as means to enhance the cytotoxic effect of conventional chemotherapeutic drugs. Among these classes, statins were the only ones that were tested in clinical trials and provided an improved therapeutic response due to their pleiotropic effects, i.e., antiproliferative, anti-inflammatory, and antioxidant [23][24][25]. Additionally, it was demonstrated that statin therapy has a cardioprotective effect on women with breast cancer who followed a therapy with anthracyclines by reducing the number of heart failure hospitalizations [26].…”

Section: Introductionmentioning

confidence: 99%

A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy

et al. 2021

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An increasing number of studies published so far have evidenced the benefits of Simvastatin (SIM) and Doxorubicin (DOX) co-treatment in colorectal cancer. In view of this, the current study aimed to investigate the pharmaceutical development of liposomes co-encapsulating SIM and DOX, by implementing the Quality by Design (QbD) concept, as a means to enhance the antiproliferative effect of the co-formulation on C26 murine colon cancer cells co-cultured with macrophages. It is known that the quality profile of liposomes is dependent on the critical quality attributes (CQAs) of liposomes (drug entrapped concentration, encapsulation efficiency, size, zeta potential, and drug release profile), which are, in turn, directly influenced by various formulation factors and processing parameters. By using the design of experiments, it was possible to outline the increased variability of CQAs in relation to formulation factors and identify by means of statistical analysis the material attributes that are critical (phospholipids, DOX and SIM concentration) for the quality of the co-formulation. The in vitro studies performed on a murine colon cancer cell line highlighted the importance of delivering the optimal drug ratio at the target site, since the balance antiproliferative vs. pro-proliferative effects can easily be shifted when the molar ratio between DOX and SIM changes.

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Section: Introductionmentioning

confidence: 99%

A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy

et al. 2021

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“…The SVM model was further tested for its robustness with DDIs involving three commonly prescribed drugs: levothyroxine, a synthetic hormone to treat hypothyroidism [35], omeprazole, a proton pump inhibitor for gastric acid-related disorders [36], and atorvastatin, an inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase used for lowering lipids concentrations to treat hypercholesterolemia [37].…”

Section: Resultsmentioning

confidence: 99%

Prediction of adverse drug reactions associated with drug-drug interactions using hierarchical classification

Kim¹,

Tatonetti

2021

Preprint

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Adverse drug reactions (ADRs) associated with drug-drug interactions (DDIs) represent a significant threat to public health. Unfortunately, most conventional methods for prediction of DDI-associated ADRs suffer from limited applicability and/or provide no mechanistic insight into DDIs. In this study, a hierarchical machine learning model was created to predict DDI-associated ADRs and pharmacological insight thereof for any drug pair. Briefly, the model takes drugs' chemical structures as inputs to predict their target, enzyme, and transporter (TET) profiles, which are subsequently utilized to assess occurrences of ADRs, with an overall accuracy of ~91%. The robustness of the model for ADR classification was validated with DDIs involving three widely prescribed drugs. The model was then applied for interstitial lung disease (ILD) associated with DDIs involving atorvastatin, identifying the involvement of multiple targets, enzymes, and transporters in ILD. The model presented here is anticipated to serve as a versatile tool for enhancing drug safety.

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“…In addition to lowering cholesterol levels, statins also have pleiotropic effects, including immunomodulatory [ 52 ], antioxidant, and anti-inflammatory [ 28 , 53 , 54 ] effects that may be related to their purported beneficial effects on Alzheimer disease. The homeostatic modulation of α7 and α4 nAChRs levels by cholesterol could be a hitherto ignored mechanism via which statins exert their neuroprotective action.…”

Section: Discussionmentioning

confidence: 99%

Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons

et al. 2020

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Neuronal α7 and α4β2 are the predominant nicotinic acetylcholine receptor (nAChR) subtypes found in the brain, particularly in the hippocampus. The effects of lovastatin, an inhibitor of cholesterol biosynthesis, on these two nAChRs endogenously expressed in rat hippocampal neuronal cells were evaluated in the 0.01–1 µM range. Chronic (14 days) lovastatin treatment augmented cell-surface levels of α7 and α4 nAChRs, as measured by fluorescence microscopy and radioactive ligand binding assays. This was accompanied in both cases by an increase in total protein receptor levels as determined by Western blots. At low lovastatin concentrations (10–100 nM), the increase in α4 nAChR in neurites was higher than in neuronal cell somata; the opposite occurred at higher (0.5–1 µM) lovastatin concentrations. In contrast, neurite α7 nAChRs raised more than somatic α7 nAChRs at all lovastatin concentrations tested. These results indicate that cholesterol levels homeostatically regulate α7 and α4 nAChR levels in a differential manner through mechanisms that depend on statin concentration and receptor localization. The neuroprotective pleomorphic effects of statins may act by reestablishing the homeostatic equilibrium.

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Statins: Complex outcomes but increasingly helpful treatment options for patients

Cited by 26 publications

References 95 publications

A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy

A Screening Study for the Development of Simvastatin-Doxorubicin Liposomes, a Co-Formulation with Future Perspectives in Colon Cancer Therapy

Prediction of adverse drug reactions associated with drug-drug interactions using hierarchical classification

Lovastatin Differentially Regulates α7 and α4 Neuronal Nicotinic Acetylcholine Receptor Levels in Rat Hippocampal Neurons

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