Effects of mineral oil administration on the pharmacokinetics, metabolism and pharmacodynamics of atorvastatin and pravastatin in mice and dogs

Gopaul, V. Sashi; Pieterman, Elsbet J.; Princen, H.M.G.; Bergenholm, Linnéa; Lundborg, Eva; Cavallin, Anders; Johansson, Magnus J.; Hawthorne, Glen; Björkbom, Anders; Hammarberg, Maria; Li, Xueqing; Jarke, Annica; Bright, Jonathan; Svensson, Lovisa; Jansson‐Löfmark, Rasmus; Abrahamsson, Bertil; Agrawal, Rahul; Hurt-Camejo, Eva

doi:10.1016/j.ejps.2021.105776

Cited by 7 publications

(8 citation statements)

References 24 publications

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“…In Syrian hamsters, which, compared with wild-type mice, have a more human-like lipoprotein profile, endotoxin has been shown to increase lowdensity-lipoprotein-cholesterol levels (Feingold et al, 1993). SAA levels in mice given mineral oil in the present study showed a trend towards higher levels than in mice given corn oil, suggesting increased cytokine-mediated inflammation with chronic mineral oil administration, in line with our recent work in wild-type mice (Gopaul et al, 2021). Liver function does not seem to have been affected, as there were similar levels of alanine aminotransferase and aspartate aminotransferase in the mineral oil and the corn oil groups.…”

Section: Discussionsupporting

confidence: 91%

“…Mineral oil can affect the absorption of some compounds, such as fatsoluble vitamins, in the gastrointestinal tract (Steigmann et al, 1952;Prescriber's Digital Reference, 2020). Our recent work in wild-type mice has indicated that short-term chronic oral administration of mineral oil as part of a Western-type diet does not affect the absorption of standard-of-care statins (Gopaul et al, 2021). However, chronic administration of mineral oil tended to cause direct, low-grade inflammation, shown by raised levels of both serum amyloid A (SAA), a marker for acute-phase inflammation, and circulating L-selectin-expressing (CD62L high ) B cells (Gopaul et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

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Chronic Oral Administration of Mineral Oil Compared With Corn Oil: Effects on Gut Permeability and Plasma Inflammatory and Lipid Biomarkers

et al. 2021

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We investigated the effects of chronic oral administration of mineral oil, versus corn oil as control, on intestinal permeability, inflammatory markers, and plasma lipids in APOE*3-Leiden.CETP mice. Mice received mineral oil or corn oil 15 or 30 μL/mouse/day for 16 weeks (15 mice/group). Intestinal permeability was increased with mineral versus corn oil 30 µL/day, shown by increased mean plasma FITC-dextran concentrations 2 h post-administration (11 weeks: 1.5 versus 1.1 μg/ml, p = 0.02; 15 weeks: 1.7 versus 1.3 μg/ml, p = 0.08). Mean plasma lipopolysaccharide-binding protein levels were raised with mineral versus corn oil 30 µL/day (12 weeks: 5.8 versus 4.4 μg/ml, p = 0.03; 16 weeks: 5.8 versus 4.5 μg/ml, p = 0.09), indicating increased intestinal bacterial endotoxin absorption and potential pro-inflammatory effects. Plasma cholesterol and triglyceride concentrations were decreased with mineral oil, without affecting liver lipids among treated groups. Fecal neutral sterol measurements indicated increased fecal cholesterol excretion with mineral oil 30 µL/day (+16%; p = 0.04). Chronic oral administration of mineral oil in APOE*3-Leiden.CETP mice increased intestinal permeability, with potential pro-inflammatory effects, and decreased plasma cholesterol and triglyceride levels. Our findings may raise concerns about the use of mineral oil as a placebo in clinical studies.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Chronic Oral Administration of Mineral Oil Compared With Corn Oil: Effects on Gut Permeability and Plasma Inflammatory and Lipid Biomarkers

et al. 2021

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“…Animal experiments tested this conjecture directly with lipophilic and hydrophilic statins, including atorvastatin and pravastatin, respectively. [ 77 ] Administered levels of mineral oil that reproduced REDUCE-IT resulted in no change in the absorption and bioavailability of these statins compared with water placebo. Indeed, there was also no difference in beneficial outcomes among patients in REDUCE-IT being administered either lipophilic or hydrophilic statins [ 77 ].…”

Section: Mixed Omega-3 Fatty Acid Treatments and Residual Cardiovascu...mentioning

confidence: 99%

“…[ 77 ] Administered levels of mineral oil that reproduced REDUCE-IT resulted in no change in the absorption and bioavailability of these statins compared with water placebo. Indeed, there was also no difference in beneficial outcomes among patients in REDUCE-IT being administered either lipophilic or hydrophilic statins [ 77 ]. One would expect mineral oil to introduce a bias against certain hydrophobic statins based on their affinity to oil, but this was not observed in either laboratory animals or in REDUCE-IT.…”

Section: Mixed Omega-3 Fatty Acid Treatments and Residual Cardiovascu...mentioning

confidence: 99%

Role of Omega-3 Fatty Acids in Cardiovascular Disease: the Debate Continues

Sherratt

Libby

Budoff

et al. 2022

Curr Atheroscler Rep

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Purpose of Review The omega-3 fatty acids (n3-FAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have recently undergone testing for their ability to reduce residual cardiovascular (CV) risk among statin-treated subjects. The outcome trials have yielded highly inconsistent results, perhaps attributable to variations in dosage, formulation, and composition. In particular, CV trials using icosapent ethyl (IPE), a highly purified ethyl ester of EPA, reproducibly reduced CV events and progression of atherosclerosis compared with mixed EPA/DHA treatments. This review summarizes the mechanistic evidence for differences among n3-FAs on the development and manifestations of atherothrombotic disease. Recent Findings Large randomized clinical trials with n3-FAs have produced discordant outcomes despite similar patient profiles, doses, and triglyceride (TG)-lowering effects. A large, randomized trial with IPE, a prescription EPA only formulation, showed robust reduction in CV events in statin treated patients in a manner proportional to achieved blood EPA concentrations. Multiple trials using mixed EPA/DHA formulations have not shown such benefits, despite similar TG lowering. These inconsistencies have inspired investigations into mechanistic differences among n3-FAs, as EPA and DHA have distinct membrane interactions, metabolic products, effects on cholesterol efflux, antioxidant properties, and tissue distribution. EPA maintains normal membrane cholesterol distribution, enhances endothelial function, and in combination with statins improves features implicated in plaque stability and reduces lipid content of plaques. Summary Insights into reductions in residual CV risk have emerged from clinical trials using different formulations of n3-FAs. Among high-risk patients on contemporary care, mixed n3-FA formulations showed no reduction in CV events. The distinct benefits of IPE in multiple trials may arise from pleiotropic actions that correlate with on-treatment EPA levels beyond TG-lowering. These effects include altered platelet function, inflammation, cholesterol distribution, and endothelial dysfunction. Elucidating such mechanisms of vascular protection for EPA may lead to new interventions for atherosclerosis, a disease that continues to expand worldwide.

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“…Although the in vitro cellular activities demonstrated that the multiple-cell-constructs supported with the spheroids can provide a highly efficient platform to crosstalk between laden cells, the use of the mineral oil to fabricate the spheroids has several limitations to apply directly in clinical applications because the remnant mineral oil may cause inflammation and harmful effects in various tissues. 70,71 For this reason, the effect of the mineral oil that was used in the formation of the spheroids on in vivo results and complex biological functions will be studied in our future work. Additionally, more biocompatible and safer hydrophobic oils [72][73][74] also could be considered for the One-SP.…”

Section: Cellular Activities Of the Printed Huvec-spheroidsmentioning

confidence: 99%

Hybrid cell constructs consisting of bioprinted cell‐spheroids

Kim

2022

Bioengineering & Transla Med

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Bioprinted cell constructs have been investigated for regeneration of various tissues. However, poor cell–cell interactions have limited their utility. Although cell‐spheroids offer an alternative for efficient cell–cell interactions, they complicate bioprinting. Here, we introduce a new cell‐printing process, fabricating cell‐spheroids and cell‐loaded constructs together without preparation of cell‐spheroids in advance. Cells in mineral oil droplets self‐assembled to form cell‐spheroids due to the oil‐aqueous interaction, exhibiting similar biological functions to the conventionally prepared cell‐spheroids. By controlling printing parameters, spheroid diameter and location could be manipulated. To demonstrate the feasibility of this process, we fabricated hybrid cell constructs, consisting of endothelial cell‐spheroids and stem cells loaded decellularized extracellular matrix/β‐tricalcium phosphate struts for regenerating vascularized bone. The hybrid cell constructs exhibited strong angiogenic/osteogenic activities as a result of increased secretion of signaling molecules and synergistic crosstalk between the cells.

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Effects of mineral oil administration on the pharmacokinetics, metabolism and pharmacodynamics of atorvastatin and pravastatin in mice and dogs

Cited by 7 publications

References 24 publications

Chronic Oral Administration of Mineral Oil Compared With Corn Oil: Effects on Gut Permeability and Plasma Inflammatory and Lipid Biomarkers

Chronic Oral Administration of Mineral Oil Compared With Corn Oil: Effects on Gut Permeability and Plasma Inflammatory and Lipid Biomarkers

Role of Omega-3 Fatty Acids in Cardiovascular Disease: the Debate Continues

Hybrid cell constructs consisting of bioprinted cell‐spheroids

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