Statins repress needle-like carbon nanotube- or cholesterol crystal-stimulated IL-1 β production by inhibiting the uptake of crystals by macrophages
In this study, we evaluated the effect of statins on crystal-induced IL-1β production in macrophages. We found that various statins, including pitavastatin, atorvastatin, fluvastatin, and lovastatin, but not squalene synthase inhibitor, repressed IL-1β release upon MWCNT stimulation. In addition, IL-1β production induced by cholesterol crystals and MSU crystals, but not by ATP or nigericin, was diminished. MWCNT-stimulated IL-1β release was dependent on the expression of NLRP3, but not AIM2, NLRC4, or MEFV. Statin-induced repression was accompanied by reduced levels of mature caspase-1 and decreased uptake of MWCNT int...
Source: Biochemical Pharmacology - April 30, 2021 Category: Drugs & Pharmacology Authors: Hongyan Cui Keisuke Soga Norimasa Tamehiro Reiko Adachi Akiko Hachisuka Akihiko Hirose Kazunari Kondo Tomoko Nishimaki-Mogami Source Type: research
Statins repress needle-like carbon nanotube- or cholesterol crystal-stimulated IL-1 β production by inhibiting the uptake of crystals by macrophages
In this study, we evaluated the effect of statins on crystal-induced IL-1β production in macrophages. We found that various statins, including pitavastatin, atorvastatin, fluvastatin, and lovastatin, but not squalene synthase inhibitor, repressed IL-1β release upon MWCNT stimulation. In addition, IL-1β production induced by cholesterol crystals and MSU crystals, but not by ATP or nigericin, was diminished. MWCNT-stimulated IL-1β release was dependent on the expression of NLRP3, but not AIM2, NLRC4, or MEFV. Statin-induced repression was accompanied by reduced levels of mature caspase-1 and decreased uptake of MWCNT int...
Source: Biochemical Pharmacology - April 30, 2021 Category: Drugs & Pharmacology Authors: Hongyan Cui Keisuke Soga Norimasa Tamehiro Reiko Adachi Akiko Hachisuka Akihiko Hirose Kazunari Kondo Tomoko Nishimaki-Mogami Source Type: research
The Effects of Single Dose Rifampin on the Pharmacokinetics of Fluvastatin in Healthy Volunteers
The objective of this study was to determine the effects of the OATP inhibitor rifampin on pharmacokinetic of Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1 compound fluvastatin. A crossover study was carried out in 10 healthy subjects who were randomized to two phases to receive fluvastatin 20 mg orally alone and following a 30-minute 600 mg IV infusion of rifampin. The results demonstrated that IV rifampin increased the mean area under the plasma fluvastatin concentration-time curve (AUC0-∞ ) by 255%, mean peak plasma concentration (Cmax ) by 254%, decreased oral volume of distribution (Vss /F)...
Source: Clinical Pharmacology and Therapeutics - April 21, 2021 Category: Drugs & Pharmacology Authors: Yue Xiang Hideaki Okochi Ivan Kozachenko Jasleen K Sodhi Lynda A Frassetto Leslie Z Benet Source Type: research
The Effects of Single Dose Rifampin on the Pharmacokinetics of Fluvastatin in Healthy Volunteers
The objective of this study was to determine the effects of the OATP inhibitor rifampin on pharmacokinetic of Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1 compound fluvastatin. A crossover study was carried out in 10 healthy subjects who were randomized to two phases to receive fluvastatin 20 mg orally alone and following a 30-minute 600 mg IV infusion of rifampin. The results demonstrated that IV rifampin increased the mean area under the plasma fluvastatin concentration-time curve (AUC0-∞ ) by 255%, mean peak plasma concentration (Cmax ) by 254%, decreased oral volume of distribution (Vss /F)...
Source: Clinical Pharmacology and Therapeutics - April 21, 2021 Category: Drugs & Pharmacology Authors: Yue Xiang Hideaki Okochi Ivan Kozachenko Jasleen K Sodhi Lynda A Frassetto Leslie Z Benet Source Type: research
Potential Alteration of Statin-Related Pharmacological Features in Diabetes Mellitus
CONCLUSION: Given that dyslipidemia frequently accompanies diabetes and statin therapy is common, more clinical studies are needed regarding the effects of diabetes on the effectiveness of these drugs.PMID:33834073 | PMC:PMC8018846 | DOI:10.1155/2021/6698743 (Source: Biomed Res)
Source: Biomed Res - April 9, 2021 Category: Research Authors: Habibeh Mashayekhi-Sardoo Stephen L Atkin Fabrizio Montecucco Amirhossein Sahebkar Source Type: research
Cytotoxic and Pro-Apoptotic Effects of a Sub-Toxic Concentration of Fluvastatin on OVCAR3 Ovarian Cancer Cells After its Optimized Formulation to Melittin Nano-Conjugates
Fluvastatin (FLV) is a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor often used to lower total and low-density lipoprotein (LDL) cholesterol and for the prevention of adverse cardiovascular events. This drug as well as melittin (MEL), the major component of honeybee venom (Apis mellifera), has shown antineoplastic activity, then representing promising approaches for cancer therapy. However, adverse effects related to the use of FLV and MEL have been reported and very few studies have been carried out to obtain an optimized formulation allowing for combining the two drugs and then maximizing the anticancer ...
Source: Frontiers in Pharmacology - February 3, 2021 Category: Drugs & Pharmacology Source Type: research
PCSK9 Inhibitors and Neurocognitive Adverse Drug Reactions: Analysis of Individual Case Safety Reports from the Eudravigilance Database
ConclusionOur results demonstrated that 22.7% of all ICSRs reporting alirocumab or evolocumab as suspect drugs described the occurrence of neuropsychiatric ADRs. The ROR showed that evolocumab and alirocumab had a higher reporting probability of neurological ADRs compared with statins. Further data from real-life contexts are needed. (Source: Drug Safety)
Source: Drug Safety - December 22, 2020 Category: Drugs & Pharmacology Source Type: research
Effects of acid and lactone forms of statins on S-warfarin 7-hydroxylation catalyzed by human liver microsomes and recombinant CYP2C9 variants (CYP2C9.1 and CYP2C9.3).
Authors: Shiozawa A, Yamaori S, Kamijo S, Ohmori S
Abstract
The inhibition of CYP2C9-mediated warfarin metabolism by acid or lactone forms of statin converted in the body and effects of CYP2C9 genetic variants on their inhibition are not fully understood. Here, the effects of acid and lactone forms of statins on S-warfarin 7-hydroxylation were investigated in vitro. S-Warfarin 7-hydroxylase activities of human liver microsomes (HLMs), recombinant CYP2C9.1 (rCYP2C9.1), and rCYP2C9.3 (Ile359Leu variant) in the presence of statins were determined by high-performance liquid chromatography. Lactone forms of at...
Source: Drug Metabolism and Pharmacokinetics - December 21, 2020 Category: Drugs & Pharmacology Tags: Drug Metab Pharmacokinet Source Type: research
Statins and C-reactive protein: in silico evidence on direct interaction.
Conclusions: This finding suggests a new mechanism of interaction between statins and CRP that could be independent of the putative cholesterol-lowering activity of statins.
PMID: 33224343 [PubMed] (Source: Archives of Medical Science)
Source: Archives of Medical Science - November 25, 2020 Category: General Medicine Tags: Arch Med Sci Source Type: research
Simvastatin Suppresses Human Breast Cancer Cell Invasion by Decreasing the Expression of Pituitary Tumor-Transforming Gene 1
Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, have been widely used to lower cholesterol and prevent cardiovascular diseases. Recent preclinical and clinical studies have shown that statins exert beneficial effects in the management of breast cancer, while the underlying mechanisms remain to be elucidated. Herein, we sought to investigate the effect of statins on the expression of pituitary tumor-transforming gene 1 (PTTG1), a critical gene involved in human breast cancer invasion and metastasis. Our results showed that PTTG1 is highly expressed in malignant Hs578T and MDA-MB-231 breast cancer cel...
Source: Frontiers in Pharmacology - November 4, 2020 Category: Drugs & Pharmacology Source Type: research
Transcriptome sequencing analysis reveals unique and shared antitumor effects of three statins in pancreatic cancer.
In conclusion, a marked difference in the intra and inter cell‑type performance of pancreatic cancer cells exposed to a variety of statins at low or high concentrations was reported herein, which may provide insights for the potential clinical use of statins in future pancreatic cancer therapeutics.
PMID: 33125137 [PubMed - as supplied by publisher] (Source: Oncology Reports)
Source: Oncology Reports - November 1, 2020 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research
Consumption of high-dose statins in patients older than 65 years in the Republic of Croatia in the period 2005 - 2015.
CONCLUSION: Consumption of all statins increased, mostly high-dose statins in the 65+ age group, the most sensitive population for adverse effects. The number of 65+ patients on high-dose statins grew much faster than the general statin user group, thus increasing the risk potential. Women are dominating all age and dose groups of statin users.
PMID: 33040840 [PubMed - as supplied by publisher] (Source: International Journal of Clinical Pharmacology and Therapeutics)
Source: International Journal of Clinical Pharmacology and Therapeutics - October 14, 2020 Category: Drugs & Pharmacology Tags: Int J Clin Pharmacol Ther Source Type: research
[ASAP] Structural Basis for Activation of Human Sirtuin 6 by Fluvastatin
ACS Medicinal Chemistry LettersDOI: 10.1021/acsmedchemlett.0c00407 (Source: ACS Medicinal Chemistry Letters)
Source: ACS Medicinal Chemistry Letters - September 29, 2020 Category: Chemistry Authors: Weijie You and Clemens Steegborn Source Type: research
Fluvastatin and atorvastatin induce programmed cell death in the brain eating amoeba Naegleria fowleri
Publication date: October 2020Source: Biomedicine & Pharmacotherapy, Volume 130Author(s): Aitor Rizo-Liendo, Ines Sifaoui, Iñigo Arberas-Jiménez, María Reyes-Batlle, José E. Piñero, Jacob Lorenzo-Morales (Source: Biomedicine and Pharmacotherapy)
Source: Biomedicine and Pharmacotherapy - August 1, 2020 Category: Drugs & Pharmacology Source Type: research
Fluvastatin and atorvastatin induce programmed cell death in the brain eating amoeba Naegleria fowleri.
In conclusion, both fluvastatin and atorvastatin could be potential new candidates for PAM therapy since they are active at low concentrations, induce low toxicity and cause PCD in the treated amoebae, hence avoiding the activation of inflammation pathways.
PMID: 32745907 [PubMed - as supplied by publisher] (Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie)
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - July 30, 2020 Category: Drugs & Pharmacology Authors: Rizo-Liendo A, Sifaoui I, Arberas-Jiménez I, Reyes-Batlle M, Piñero JE, Lorenzo-Morales J Tags: Biomed Pharmacother Source Type: research
