Isolated ipsilateral ptosis associated with ventral midbrain infarction: a case report and literature review.

Documented cases of ipsilateral ptosis caused by midbrain infarction remain rare. Herein, we present a patient with isolated ipsilateral ptosis that was initially considered to be a consequence of myasthenia gravis but was subsequently attributed to ventral midbrain infarction. We also discuss the possible underlying mechanisms; ipsilateral ptosis in our patient was attributed to selective damage of the levator palpebral muscle branch of the oculomotor nerve. The patient was started on aspirin (200 mg once daily) and atorvastatin (40 mg once daily). Improvement in ptosis occurred from day 5 of admission, and the patient was subsequently discharged. Ptosis disappeared 1 month after onset. This report describes an extremely rare case of ventral midbrain infarction presenting with isolated ipsilateral ptosis. Careful examination, including magnetic resonance imaging, is essential in such patients, especially in those with multiple cerebrovascular risk factors.

Atorvastatin lowers breast cancer risk by reversing an early tumorigenic signature.

Breast cancer remains a significant health challenge with complex molecular mechanisms. While many studies have explored genetic markers in breast carcinogenesis, few have studied the potential impact of pharmacological interventions such as Atorvastatin on its genetic landscape. This study aimed to elucidate the molecular distinctions between normal and tumor-adjacent tissues in breast cancer and to investigate the potential protective role of atorvastatin, primarily known for its lipid-lowering effects, against breast cancer. Searching the Gene Expression Omnibus database identified two datasets, GSE9574 and GSE20437, comparing normal breast tissues with tumor-adjacent samples, which were merged, and one dataset, GSE63427, comparing paired pre- and post-treated patients with atorvastatin. Post-ComBat application showed merged datasets' consistency, revealing 116 DEGs between normal and tumor-adjacent tissues. Although initial GSE63427 data analysis suggested a minimal impact of atorvastatin, 105 DEGs post-treatment were discovered. Thirteen genes emerged as key players, both affected by Atorvastatin and dysregulated in tumor-adjacent tissues. Pathway analysis spotlighted the significance of these genes in processes like inflammation, oxidative stress, apoptosis, and cell cycle control. Moreover, there was a noticeable interaction between these genes and the immunological microenvironment in tumor-adjacent tissues, with Atorvastatin potentially altering the suppressive immune landscape to favor anti-tumor immunity. Survival analysis further highlighted the prognostic potential of the 13-gene panel, with 12 genes associated with improved survival outcomes. The 13-gene signature offers promising insights into breast cancer's molecular mechanisms and atorvastatin's potential therapeutic role. The preliminary findings advocate for an in-depth exploration of atorvastatin's impact on.

[Atorvastatin promotes the healing of alveolar bone defect in rats and its effect on Wnt/ß-catenin signaling pathway].

PURPOSE: To investigate the therapeutic effect of atorvastatin on alveolar bone defect model in rats, and to observe the effect of atorvastatin on Wnt/ß-catenin. METHODS: Thirty rats were randomly divided into normal group (group N), model group (group M) and atorvastatin administration group (group ATV). Except group N, bone defects were made in other rats' alveolar bone to construct alveolar bone defect model. After successful modeling, 20 mg/kg atorvastatin suspension was administered by gavage in group ATV, and the same amount of sodium carboxymethyl cellulose solution was administered by gavage in group N and group M for twenty-one days. After the last administration, tail vein blood was collected to detect the concentrations of serum osteoprotegerin (OPG), alkaline phosphatase (ALP) and osteocalcin (BPG). H-E staining was used to observe the pathological changes of maxillary defect area, and lane Sandhu score was performed. Tartrate resistant acid phosphatase(TRAP) staining was used to detect the number of osteoclasts in the defect area. Real time fluorescence quantitative PCR(RT-qPCR) and Western blot(WB) were used to detect Wnt, ß-catenin and Runx2 mRNA protein expression. Statistical analysis was performed with SPSS 23.0 software package. RESULTS: Compared with group N, the concentrations of OPG, ALP, BGP and Lane Sandhu score in group M decreased, and the number of osteoclasts increased. Compared with group M, the concentrations of OPG, ALP and BGP and lane Sandhu score in group ATV increased, and the number of osteoclasts decreased. After H-E staining, the amount of bone formation in maxillary defect area in group N was more,there was fewer bone tissues in the defect area in group M, the amount of bone tissues in the defect area increased in group ATV. Compared with group N, Wnt, ß-catenin and Runx2 mRNA protein decreased. Compared with group M, Wnt, ß-catenin and Runx2 mRNA protein expression increased. CONCLUSIONS: Atorvastatin can promote the healing of alveolar bone defect and accelerate bone reconstruction in rat models. This effect may be related to the activation of Wnt/ß-catenin signaling pathway.

PKMYT1 knockdown inhibits cholesterol biosynthesis and promotes the drug sensitivity of triple-negative breast cancer cells to atorvastatin.

Triple negative breast cancer (TNBC) as the most aggressive molecular subtype of breast cancer is characterized by high cancer cell proliferation and poor patient prognosis. Abnormal lipid metabolism contributes to the malignant process of cancers. Study observed significantly enhanced cholesterol biosynthesis in TNBC. However, the mechanisms underlying the abnormal increase of cholesterol biosynthesis in TNBC are still unclear. Hence, we identified a member of the serine/threonine protein kinase family PKMYT1 as a key driver of cholesterol synthesis in TNBC cells. Aberrantly high-expressed PKMYT1 in TNBC was indicative of unfavorable prognostic outcomes. In addition, PKMYT1 promoted sterol regulatory element-binding protein 2 (SREBP2)-mediated expression of enzymes related to cholesterol biosynthesis through activating the TNF/ TNF receptor-associated factor 1 (TRAF1)/AKT pathway. Notably, downregulation of PKMYT1 significantly inhibited the feedback upregulation of statin-mediated cholesterol biosynthesis, whereas knockdown of PKMYT1 promoted the drug sensitivity of atorvastatin in TNBC cells. Overall, our study revealed a novel function of PKMYT1 in TNBC cholesterol biosynthesis, providing a new target for targeting tumor metabolic reprogramming in the cancer.

Preincubation-dependent inhibition of organic anion transporting polypeptide 2B1.

Preincubation with inhibitor in organic anion transporting polypeptide (OATP) in vitro assays may increase the inhibition potency of inhibitors compared to conventional inhibition assays with only short inhibitor coincubation with substrate. The decrease in IC50 may affect prediction of drug-drug interactions (DDI) involving these transporters and inhibitors. Only few drugs, however, have been assessed for the preincubation-dependent inhibition of the OATP2B1 transporter. Therefore, we studied the effect of preincubation on OATP2B1 inhibition with five known OATP2B1 inhibitors (atorvastatin, erlotinib, ezetimibe, ticagrelor and simeprevir) in HEK293 cells transiently overexpressing OATP2B1. IC50 values were determined with and without inhibitor preincubation for 20 min with three different OATP2B1 substrates (dibromofluorescein, DBF; 5-carboxyfluorescein, 5-CF; estrone sulfate). Atorvastatin, ezetimibe, and simeprevir displayed more than 2-fold lower IC50 values after preincubation with at least one of the tested substrates. Altogether, 4 out of 15 inhibitor/substrate combinations exhibited more than 2-fold potentiation of IC50 after inhibitor preincubation. In addition, preincubation by itself, without inhibitor present with the substrate, resulted in more than 50% inhibition of OATP2B1-mediated uptake of DBF and/or 5-CF by atorvastatin, ticagrelor and simeprevir. Thus, erlotinib was the only inhibitor with no indication of potentiation of inhibition by preincubation with any of the tested substrates. In conclusion, preincubation resulted in inhibitor- and substrate-dependent inhibition of OATP2B1. These results support the conclusion that to reduce the risk of false negative DDI prediction, preincubation should be considered also in OATP2B1 inhibition assays.

Rhabdomyolysis Risk: The Dangers of Tribulus Terrestris, an Over-the-Counter Supplement.

BACKGROUND Over-the-counter (OTC) supplement use is a very common practice within the United States. Supplements are not tightly regulated by the Food and Drug Administration. There are many case reports involving OTC supplement adverse effects and medication interactions, but there remains minimal clinical research regarding these subjects. Rhabdomyolysis is one interaction and adverse effect frequently documented in case reports among a variety of OTC supplements, although, to date, there is no documentation of rhabdomyolysis occurring from an interaction between the supplement Tribulus terrestris and atorvastatin. CASE REPORT A 71-year-old man presented to the Emergency Department in rhabdomyolysis with a mild transaminitis after taking the over-the-counter supplement Tribulus terrestris while on long-term atorvastatin. His rhabdomyolysis peaked at day 4 after cessation of the Tribulus and atorvastatin and aggressive fluid resuscitation with a normal saline bolus at admission followed by a D5 sodium bicarbonate drip later transitioned to a normal saline drip with subsequent down-trending of the creatinine phosphokinase levels. CONCLUSIONS Tribulus terrestris is an herbal supplement used for erectile dysfunction and energy. Recent research suggests it to be a moderate CYP 3A4 inhibitor that plays a significant role in metabolism of statin and many other commonly prescribed medications. This may put patients at increased risk of developing serious adverse effects, including rhabdomyolysis and drug-induced liver injury. Screening patients for over-the-counter supplement use and educating them on the potential risks of their use is extremely important for inpatient and outpatient healthcare professionals to avoid dangerous medication interactions.

Evaluation of the effect of atorvastatin on corneal endothelial cells during the initial 12-month period after acute coronary syndrome.

PURPOSE: It was aimed to compare corneal endothelial changes during the initial 12-month period in which patients started using atorvastatin after a diagnosis of acute coronary syndrome (ACS). METHODS: Forty-six participants (group 1) who underwent cardiac angioplasty and stenting for ACS and started using 80 mg atorvastatin in the early period were included in the study. In the study, a control group comprising 71 healthy adults (group 2) was included. These individuals did not use medication for any known systemic disease, had never taken statins, had no history of ocular surgery, and did not have any cornea-related eye diseases. Baseline and 12th month endothelial evaluations of group 1 and 2 participants were compared using specular microscopy. RESULTS: There were 28 female and 18 male participants in group 1 and 48 female and 23 male participants in group 2 (P = 0.455). The mean baseline corneal endothelial cell density (CECD) was not significantly higher in group 1 compared to group 2 (2471.4 ± 200 cells/mm2 vs 2428.2 ± 539.8 cells/mm2, P = 0.230). When the change between baseline and 12th month CECD was examined, the decrease in group 2 was significantly different from that in group 1 (-15,2 ± 31,9 and -44,8 ± 49,6, P = 0,002). Although the percentage of hexagonal cells decreased significantly in group 2 participants, no significant change was observed in group 1 (respectively; P < 0.001, P = 0.073). The endothelial cell coefficient of variation did not differ significantly in group 1 participants over a 1-year period (P = 0.192), and a significant increase was observed in group 2 (P < 0.001). CONCLUSION: This study revealed that atorvastatin may have a positive effect on corneal endothelium cell density and morphology.

Topical application of simvastatin acid sodium salt and atorvastatin calcium salt in vitiligo patients. Results of the randomized, double-blind EVRAAS pilot study.

Contemporary treatment of vitiligo remains a great challenge to practitioners. The vast majority of currently conducted clinical trials of modern therapeutic methods are focused on systemic medications, while there is only a very limited number of reports on new topical treatment in vitiligo. With their pleiotropic activities statins turned out to be efficient in the treatment of various autoimmune/autoinflammatory disorders. The randomized, double-blind placebo-controlled study of topical administration of the active forms of simvastatin and atorvastatin has been designed to evaluate their efficacy in patients with vitiligo. The study was registered in clinicaltrials.gov (registration number NCT03247400, date of registration: 11th August 2017). A total of 24 patients with the active form of non-segmental vitiligo were enrolled in the study. The change of absolute area of skin lesions, body surface area and vitiligo area scoring index were evaluated throughout the 12 week application of ointments containing simvastatin and atorvastatin. Measurements were performed with planimetry and processed using digital software. Use of active forms of simvastatin and atorvastatin did not result in a significant repigmentation of the skin lesions throughout the study period. Within the limbs treated with topical simvastatin, inhibition of disease progression was significantly more frequent than in the case of placebo (p = 0.004), while the difference was not statistically significant for atorvastatin (p = 0.082). Further studies of topical simvastatin in vitiligo patients should be considered.

Statin Usage in Peripheral Arterial Disease Patients.

OBJECTIVES: Atherosclerotic cardiovascular disease (ASCVD) events have been shown to occur at higher frequency in patients with peripheral arterial disease (PAD). In this study, our aim is to evaluate whether statin is being used appropriately in patients with PAD and also evaluate its usage with the number of vascular beds involved. MATERIALS AND METHODS: This retrospective cross-sectional study reviewed data of patients with a confirmed diagnosis of PAD based on invasive or noninvasive imaging. Demographic, clinical, laboratory, and treatment data collected were described using descriptive statistics. Multiple logistic regression analysis was conducted to determine the predictors for the prescription of statins (HIS). High-intensity statin therapy was defined as atorvastatin ≥40 mg per day, rosuvastatin ≥20 mg per day, or simvastatin ≥80 mg per day, according to American College of Cardiology (ACC)/American Heart Association (AHA) guidelines. RESULTS: We analyzed data from 166 patients who met the inclusion criteria. The mean age was 63.34 years. The most common comorbidity was diabetes mellitus (DM) (68.86%). Statins were used in 82% of patients, among whom only 39% were on high-intensity statins. Multiple logistic regression analysis revealed that patients with cerebrovascular disease (CVD) [odds ratio (OR) = 0.19, 95% confidence interval (CI) = 0.06-0.61, p = 0.005], on oral anticoagulants (OAC) (OR = 0.16, 95% CI = 0.04-0.62, p = 0.008) and on dual antiplatelet therapy (DAPT) (OR = 0.20, 95% CI = 0.08-0.47, p < 0.000) had lower odds of receiving lower extremity revascularization (LIS) therapy. CONCLUSION: Despite having a high risk of future adverse cardiac events, patients with PAD are less likely to receive appropriate statin therapy. Involvement of more vascular beds was associated with higher chances of initiating high-intensity statin.

Atorvastatin ameliorates diabetic nephropathy through inhibiting oxidative stress and ferroptosis signaling.

Clinically, statins have long been used for the prevention and treatment of chronic renal diseases, however, the underlying mechanisms are not fully elucidated. The present study investigated the effects of atorvastatin on diabetes renal injury and ferroptosis signaling. A mouse model of diabetes was established by the intraperitoneal injection of streptozotocin (50 mg/kg/day) plus a high fat diet with or without atorvastatin treatment. Diabetes mice manifested increased plasma glucose and lipid profile, proteinuria, renal injury and fibrosis, atorvastatin significantly lowered plasma lipid profile, proteinuria, renal injury in diabetes mice. Atorvastatin reduced renal reactive oxygen species (ROS), iron accumulation and renal expression of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), transferrin receptor 1 (TFR1), and increased renal expression of glutathione peroxidase 4 (GPX4), nuclear factor erythroid 2-related factor (NRF2) and ferritin heavy chain (FTH) in diabetes mice. Consistent with the findings in vivo, atorvastatin prevented high glucose-induced ROS formation and Fe2+ accumulation, an increase in the expression of 4-HNE, MDA and TFR1, and a decrease in cell viability and the expression of NRF2, GPX4 and FTH in HK2 cells. Atorvastatin also reversed ferroptosis inducer erastin-induced ROS production, intracellular Fe2+ accumulation and the changes in the expression of above-mentioned ferroptosis signaling molecules in HK2 cells. In addition, atorvastatin alleviated high glucose- or erastin-induced mitochondria injury. Ferroptosis inhibitor ferrostatin-1 and antioxidant N-acetylcysteine (NAC) equally reversed the expression of high glucose-induced ferroptosis signaling molecules. Our data support the notion that statins can inhibit diabetes-induced renal oxidative stress and ferroptosis, which may contribute to statins protection of diabetic nephropathy.

The Anti-Atherosclerotic Effects of Endothelin Receptor Antagonist, Bosentan, in Combination with Atorvastatin-An Experimental Study.

Bosentan, an endothelin receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male ApoE-/- mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin, and mice were randomized into four groups: (1) control/COG: no intervention; (2) ΒOG: bosentan 100 mg/kg/day per os; (3) ATG: atorvastatin 20 mg/kg/day per os; and (4) BO + ATG: combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix metalloproteinases (MMP-2, -3, -9), and TIMP-1 were determined. The percentage of lumen stenosis was significantly lower across all treated groups: BOG: 19.5 ± 2.2%, ATG: 12.8 ± 4.8%, and BO + ATG: 9.1 ± 2.7% compared to controls (24.6 ± 4.8%, p < 0.001). The administration of both atorvastatin and bosentan resulted in significantly higher collagen content and thicker fibrous cap versus COG (p < 0.01). All intervention groups showed lower relative intra-plaque concentrations of MCP-1, MMP-3, and MMP-9 and a higher TIMP-1concentration compared to COG (p < 0.001). Importantly, latter parameters presented lower levels when bosentan was combined with atorvastatin compared to COG (p < 0.05). Bosentan treatment in diabetic, atherosclerotic ApoE-/- mice delayed the atherosclerosis progression and enhanced plaques' stability, showing modest but additive effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.

Synthesis of zero valent copper/iron nanoparticles using Piper betle leaves for the removal of pharmaceutical contaminant atorvastatin.

In this study, bimetallic Cu-Fe nanoparticles were synthesized using the green approach with Piper betle leaves, and the removal efficiency of one of the pharmaceutical compounds, Atorvastatin, was investigated. UV, SEM, FTIR, EDAX, particle size, and zeta potential measurements were used to confirm nanoparticle fabrication. The removal efficiency of Atorvastatin (10 mg/L) by bimetallic Cu-Fe nanoparticles was 67% with a contact time of 30 min at pH 4, the adsorbent dosage of 0.2 g/L, and stirring at 100 rpm. Piper betle bimetallic Cu-Fe nanoparticles have demonstrated excellent stability, reusability, and durability, even after being reused five times. Furthermore, the synthesized bimetallic Cu-Fe nanoparticles demonstrated remarkable antimicrobial properties against gram-negative strains such as Escherichia coli and Klebsiella pneumoniae, gram-positive strains such as Staphylococcus aureus and Bacillus subtilis, and fungi such as Aspergillus niger. In addition, the antioxidant properties of the synthesized bimetallic Cu-Fe nanoparticles were assessed using the DPPH radical scavenging assay. The results indicated that the nanoparticles had good antioxidant activity. Thus, using Piper betle extract to make Cu-Fe nanoparticles made the procedure less expensive, chemical-free, and environmentally friendly, and the synthesized bimetallic Cu-Fe nanoparticles helped remove the pharmaceutical compound Atorvastatin from wastewater.

Atorvastatin improved ulcerative colitis in association with gut microbiota-derived tryptophan metabolism.

AIMS: Atorvastatin is a commonly used cholesterol-lowering drug that possesses non-canonical anti-inflammatory properties. However, the precise mechanism underlying its anti-inflammatory effects remains unclear. MATERIALS AND METHODS: The acute phase of ulcerative colitis (UC) was induced using a 5 % dextran sulfate sodium (DSS) solution for 7 consecutive days and administrated with atorvastatin (10 mg/kg) from day 3 to day 7. mRNA-seq, histological pathology, and inflammatory response were determined. Intestinal microbiota alteration, tryptophan, and its metabolites were analyzed through 16S rRNA sequencing and untargeted metabolomics. KEY FINDINGS: Atorvastatin relieved the DSS-induced UC in mice, as evidenced by colon length, body weight, disease activity index score and pathological staining. Atorvastatin treatment reduced the level of pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Atorvastatin also relieved the intestinal microbiota disorder caused by UC and decreased the proliferation of pernicious microbiota such as Akkermansia and Bacteroides. Atorvastatin dramatically altered tryptophan metabolism and increased the fecal contents of tryptophan, indolelactic acid (ILA), and indole-3-acetic acid (IAA). Furthermore, atorvastatin enhanced the expression level of aryl hydrocarbon receptor (AhR) and interleukin-22 (IL-22) and further promoted the expression level of intestinal tight junction proteins, such as ZO-1 and occludin, in colitis mice. SIGNIFICANCE: These findings indicated that atorvastatin could alleviate UC by regulating intestinal flora disorders, promoting microbial tryptophan metabolism, and repairing the intestinal barrier.

The Effect of Different Statin-Based Lipid-Lowering Strategies on C-Reactive Protein Levels in Patients With Stable Coronary Artery Disease.

BACKGROUND: Statins are lipid-lowering drugs with favorable anti-inflammatory effects. This study aimed to explore different statin-based lipid-lowering strategies to reduce high-sensitivity C-reactive protein (hs-CRP). HYPOTHESIS: The hypothesis is that different statin-based lipid-lowering strategies might reduce hs-CRP. METHODS: This retrospective study included 3653 patients who underwent percutaneous coronary intervention (PCI). Three statin-based lipid-lowering strategies were investigated, including different types of statins (atorvastatin vs. rosuvastatin), statin combined with ezetimibe therapy (vs. without), and intensive statin therapy (vs. regular). The hs-CRP levels and blood lipid indicators were measured at baseline and after 1-month lipid-lowering therapy. Multivariable linear regression analysis and structural equation mode analysis were conducted to verify the association between different lipid-lowering strategies, Δhs-CRP (%) and ΔLDL-C (%). RESULTS: Totally, 3653 patients were enrolled with an average age of 63.81 years. Multivariable linear regression demonstrated that statin combined with ezetimibe therapy was significantly associated with decreased Δhs-CRP (%) (ß = -0.253, 95% CI: [-0.501 to -0.005], p = 0.045). The increased ΔLDL-C (%) was an independent predictor of elevated levels of Δhs-CRP (%) (ß = 0.487, 95% CI: [0.15-0.824], p = 0.005). Furthermore, structural equation model analysis proved that statin combined with ezetimibe therapy (ß = -0.300, p < 0.001) and intensive statin therapy (ß = -0.032, p = 0.043) had an indirect negative effect on Δhs-CRP via ΔLDL-C. CONCLUSIONS: Compared with routine statin use, statin combined with ezetimibe therapy and intensive statin therapy could further reduce hs-CRP levels.

Design, optimization and characterization of atorvastatin loaded chitosan-based polyelectrolyte complex nanoparticles based transdermal patch.

AIM: Atorvastatin (ATO) loaded chitosan-based polyelectrolyte complex nanoparticles (PECN) incorporated transdermal patch was developed to enhance its skin permeability and bioavailability. METHODOLOGY: The ATO loaded PECN were prepared by ionic gelation method and optimized by Box-Behnken design. The optimized batches were evaluated for physicochemical characteristics, in vitro, ex vivo, cell line and stability studies. The optimized ATO-PECN were incorporated into transdermal patches by solvent evaporation method and evaluated for their physicochemical properties, ex vivo skin permeation, in vivo pharmacokinetics and stability study. RESULTS: The optimized batch of ATO-PECN had average size of 219.2 ± 5.98 nm with 82.68 ± 2.63 % entrapment and 25.41 ± 3.29 mV zeta potential. ATO-PECN showed sustained drug release and higher skin permeation. The cell line study showed that ATO-PECN increased the cell permeability of ATO as compared to ATO suspension. ATO-PECN loaded transdermal patch showed higher skin permeation. The in vivo pharmacokinetic study revealed that the ATO-PECN transdermal patch showed significant (p < 0.05) increase in pharmacokinetic parameters as compared to marketed oral tablet, confirming enhancement in bioavailability of ATO. CONCLUSIONS: The results of the present work concluded that the ATO-PECN loaded transdermal patch is a promising novel drug delivery system for poorly bioavailable drugs.

The Oxidative Stress Markers' Protective Influence of Sea Buckthorn and Grape Extracts in Atorvastatin-Treated Hyperlipidemic Rats.

Free radicals and reactive oxygen species initiate when the oxidative stress arises. (1) Background: The effect of natural molecules on oxidative stress in hyperlipidemic rats, taking statins, was observed. (2) Methods: One hundred and twelve white Wistar rats, males and females, were divided into seven: Group I received 20 mg of atorvastatin while groups II and III received a combination of 20 mg of atorvastatin and 100 mg of Sea buckthorn and grape extract. Groups IV and V received 100 mg of Sea buckthorn and grape extract, while groups VI and VII received only high-fat diet (HFD) and normal rodents' fodder. After two and six months, rats were euthanized, and blood was gathered to measure the main paraclinical values and total antioxidant capacity (TAC). Also, the liver and kidney were stored for the organs' cytoarchitecture. For statistics, two-way analysis of variance (ANOVA), was performed. (3) Results: HFD produced hyperlipidemia, accompanied by augmented serum and hepatic oxidative stress markers, in addition to a reduction in antioxidant enzyme activities and glutathione levels. Polyphenolic substances proven efficient against HFD caused oxidative stress. (4) Conclusions: Atorvastatin heightened the histological injuries caused by the fatty diet, but these were diminished by taking atorvastatin in combination with 100 mg/kg of plant extracts.

3D printed scaffolds as delivery devices for nanocrystals: A proof of concept loading Atorvastatin with enhanced properties for sublingual route of administration.

Increasing the solubility of drugs is a recurrent objective of pharmaceutical research, and one of the most widespread strategies today is the formulation of nanocrystals (NCs). Beyond the many advantages of formulating NCs, their incorporation into solid dosage forms remains a challenge that limits their use. In this work, we set out to load Atorvastatin NCs (ATV-NCs) in a delivery device by combining 3D scaffolds with an "in situ" loading method such as freeze-drying. When comparing two infill patterns for the scaffolds at two different percentages, the one with the highest NCs load was chosen (Gyroid 20 % infill pattern, 13.8 ± 0.5 mg). Colloidal stability studies of NCs suggest instability in acidic media, and therefore, the system is postulated for use as a sublingual device, potentially bypassing stomach and hepatic first-pass effects. An ad hoc dissolution device was developed to mimic the release of actives. The nanometric size and properties acquired in the process were maintained, mainly in the dissolution rate and speed, achieving 100 % dissolution of the content in 180 s. Based on these results, the proof of concept represents an innovative approach to converting NCs suspensions into solid dosage forms.

Hesperidin, vanillic acid, and sinapic acid attenuate atorvastatin-induced mitochondrial dysfunction via inhibition of mitochondrial swelling and maintenance of mitochondrial function in pancreas isolated mitochondria.

It has been reported that lipophilic statins such as atorvastatin can more readily penetrate into ß-cells and reach the mitochondria, resulting in mitochondrial dysfunction, oxidative stress, decrease in insulin release. Many studies have shown that natural products can protect mitochondrial dysfunction induced by drug in different tissue. We aimed to explore mitochondrial protection potency of hesperidin, vanillic acid, and sinapic acid as natural compounds against mitochondrial dysfunction induced by atorvastatin in pancreas isolated mitochondria. Mitochondria were isolated form rat pancreas and directly treated with toxic concentration of atorvastatin (500 µM) in presence of various concentrations hesperidin, vanillic acid, and sinapic acid (1, 10, and 100 µM) separately. Mitochondrial toxicity parameters such as the reactive oxygen species (ROS) formation, succinate dehydrogenases (SDH) activity, mitochondrial swelling, depletion of glutathione (GSH), mitochondrial membrane potential (MMP) collapse, and malondialdehyde (MDA) production were measured. Our findings demonstrated that atorvastatin directly induced mitochondrial toxicity at concentration of 500 µM and higher in pancreatic mitochondria. Except MDA, atorvastatin caused significantly reduction in SDH activity, mitochondrial swelling, ROS formation, depletion of GSH, and collapse of MMP. While, our data showed that all three protective compounds at low concentrations ameliorated atorvastatin-induced mitochondrial dysfunction with the increase of SDH activity, improvement of mitochondrial swelling, MMP collapse and mitochondrial GSH, and reduction of ROS formation. We can conclude that hesperidin, vanillic acid, and sinapic acid can directly reverse the toxic of atorvastatin in rat pancreas isolated mitochondria, which may be beneficial for protection against diabetogenic-induced mitochondrial dysfunction in pancreatic ß-cells.

Atorvastatin combined with imipenem alleviates lung injury in sepsis by inhibiting neutrophil extracellular trap formation via the ERK/NOX2 signaling pathway.

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms. Despite major advances in diagnosis and technology, morbidity and mortality remain high. The level of neutrophil extracellular traps (NETs) is closely associated with the progression and prognosis of sepsis, suggesting the regulation of NET formation as a new strategy in sepsis treatment. Owing to its pleiotropic effects, atorvastatin, a clinical lipid-lowering drug, affects various aspects of sepsis-related inflammation and immune responses. To align closely with clinical practice, we combined it with imipenem for the treatment of sepsis. In this study, we used a cecum ligation and puncture-induced lung injury mouse model and employed techniques including western blot, immunofluorescence, and enzyme-linked immunosorbent assay to measure the levels of NETs and other sepsis-related lung injury indicators. Our findings indicate that atorvastatin effectively inhibited the formation of NETs. When combined with imipenem, it significantly alleviated lung injury, reduced systemic inflammation, and improved the 7-day survival rate of septic mice. Additionally, we explored the inhibitory mechanism of atorvastatin on NET formation in vitro, revealing its potential action through the ERK/NOX2 pathway. Therefore, atorvastatin is a potential immunomodulatory agent that may offer new treatment strategies for patients with sepsis in clinical settings.

Statin-induced, immune-mediated necrotising myopathy triggered by malignancy successfully treated with immunosuppression.

Statin-induced immune-mediated necrotising myopathy (IMNM) is an inflammatory myopathy that can present as proximal muscle weakness and, in some cases, as dysphagia and respiratory distress. In this report, we present a case of statin-induced IMNM in a 78-year-old male. The patient had significantly high levels of creatinine kinase and myoglobinuria and experienced gradual weakness in the proximal muscles for 1 month after initiating a 20 mg dose of Atorvastatin 10 months before admission. Rapid clinical improvement was observed with the use of high-dose glucocorticoids in conjunction with methotrexate.