Administration Of Atorvastatin Research Articles

Probiotics combined with atorvastatin administration in the treatment of hyperlipidemia: A randomized, double-blind, placebo-controlled clinical trial.

Hyperlipidemia is a common feature of chronic diseases. The aim of this work was designed to assess the role of probiotics (Lactobacillus casei Zhang, Bifidobactetium animalis subsp. lactis V9, and Lactobacillus plantarum P-8) in the treatment of hyperlipidemia. Thirty three patients with hyperlipidemia were randomly divided into a probiotic group (n = 18) and a control group (n = 15). The probiotic group was administered probiotics (2 g once daily) and atorvastatin 20 mg (once daily), and the control group was administered a placebo (2 g once daily) and atorvastatin 20 mg (once daily). Serum and fecal samples were gathered for subsequent analyses. Time had a significant effect on the total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) levels in the probiotic and control groups (P < .05). The gut microbial abundance in the probiotic group was markedly higher than that in the control group following 3-month probiotic treatment (P < .05). At the phylum level, probiotics exerted no notable effects on the relative abundance of Firmicutes, Bacteroidetes, and Actinobacteria but elevated that of Tenericutes and reduced Proteobacteria. At the genus level, probiotics increased the relative abundance of Bifidobacterium, Lactobacillus, and Akkermansia, and decreased that of Escherichia, Eggerthella, and Sutterella relative to the control group in months 1, 2, and 3 (P < .05). Probiotics optimize the gut microbiota structure and decrease the amount of harmful bacteria in patients with hyperlipidemia. Probiotics can influence the composition of gut microorganisms and increase their diversity and abundance in vivo. It is recommended to use probiotics combined with atorvastatin to treat patients with hyperlipidemia.

Pharmacokinetic interaction between regorafenib and atorvastatin in rats.

Regorafenib is used in the treatment of colorectal cancer and hepatocellular carcinoma. Due to the co-morbidity of hyperlipidemia in these conditions, statins, including atorvastatin, are used as potential adjuvant therapy agents. Both regorafenib and atorvastatin are metabolized by CYP3A4. In addition, atorvastatin is a P-gp and BCRP substrate, whereas regorafenib and its active metabolites M-2 and M-5 are inhibitors of these transporters. Hence, the concomitant use of both drugs may increase the risk of a clinically significant drug-drug interaction. Therefore, the present study aimed to assess the pharmacokinetic interactions of atorvastatin and regorafenib and their active metabolites. Male Wistar rats were assigned to three groups (eight animals in each) and were orally administered: regorafenib and atorvastatin (IREG+ATO), a carrier with regorafenib (IIREG), and atorvastatin with a carrier (IIIATO). Blood samples were collected for 72h. UPLC-MS/MS was the method of measurement of regorafenib and atorvastatin concentrations. The pharmacokinetic parameters were calculated with a non-compartmental model. A single administration of atorvastatin increased the exposure to regorafenib and its active metabolites. In the IREG+ATO group, the Cmax, AUC0-t, and AUC0-∞ of regorafenib increased 2.7, 3.2, and 3.2-fold, respectively. Atorvastatin also significantly increased the Cmax, AUC0-t, and AUC0-∞ of both regorafenib metabolites. Regorafenib, in turn, decreased the AUC0-t and AUC0-∞ of 2-OH atorvastatin by 86.9% and 67.3%, and the same parameters of 4-OH atorvastatin by 45.0% and 46.8%, respectively. This animal model study showed a significant pharmacokinetic interaction between regorafenib and atorvastatin. While this interaction may be clinically significant, this needs to be confirmed in clinical trials involving cancer patients.

A novel mouse model of familial combined hyperlipidemia and atherosclerosis.

Within the context of residual cardiovascular risk in post-statin era, emerging evidence from epidemiologic and human genetic studies have demonstratedthattriglyceride (TG)-rich lipoproteinsand their remnants are causally related to cardiovascular risk. While,carriers of loss-of-function mutations of ApoC3 havelow TG levelsand are protected from cardiovascular disease (CVD). Of translational significance,siRNAs/antisense oligonucleotide (ASO) targeting ApoC3 is beneficial for patients with atheroscleroticCVD. Therefore, animal models of atherosclerosiswith bothhypercholesterolemia and hypertriglyceridemia are important for the discovery of novel therapeutic strategies targeting TG-lowering on top of traditional cholesterol-lowering.In this study, we constructed a novel mouse model of familial combined hyperlipidemia through inserting a human ApoC3 transgene(hApoC3-Tg) into C57BL/6 J mice and injecting a gain-of-function variant of adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-D377Y concurrently with high cholesterol diet (HCD) feeding for 16 weeks. In the last 10 weeks, hApoC3-Tg mice were orally treated with a combination of atorvastatin (10 mg·kg-1·d-1) and fenofibrate (100 mg·kg-1·d-1). HCD-treated hApoC3-Tg mice demonstrated elevated levels of serum TG, total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C). Oral administration of atorvastatin and fenofibrate significantly decreased the plaque sizes of en face aorta, aortic sinus and innominate artery accompanied by improved lipid profileand distribution. In summary,this novel mouse model is of considerable clinical relevance for evaluation of anti-atherosclerotic drugsby targeting both hypercholesterolemia and hypertriglyceridemia.

Identification of MGMT promoter methylation as a specific lipid metabolism biomarker, reveals the feasibility of atorvastatin application in glioblastoma

BackgroundGlioblastoma is one of the deadliest tumors, and limited improvement in managing glioblastoma has been achieved in the past decades. The unmethylated promoter area of 6-O-Methylguanine-DNA Methyltransferase (MGMT) is a significant biomarker for recognizing a subset of glioblastoma that is resistant to chemotherapy. Here we identified MGMT methylation can also work as a specific biomarker to classify the lipid metabolism patterns between methylated and unmethylated glioblastoma and verify the potential novel therapeutic strategy for unmethylated MGMT glioblastoma. MethodsLiquid Chromatograph Mass Spectrometer has been applied for non-targeted metabolome and targeted lipidomic profiling to explore the metabolism pattern correlated with MGMT promoter methylation. Transcriptome has been performed to explore the biological differences and the potential mechanism of lipid metabolism in glioblastoma samples. In vivo and ex vivo assays were performed to verify the anti-tumor activity of atorvastatin in the administration of glioblastoma. ResultsMulti-omics assay has described a significant difference in lipid metabolism between MGMT methylated and unmethylated glioblastoma. Longer and unsaturated fatty acyls were found enriched in MGMT-UM tumors. Lipid droplets have been revealed remarkably decreased in MGMT unmethylated glioblastoma. In vivo and ex vivo assays revealed that atorvastatin and also together with temozolomide showed significant anti-tumor activity, and atorvastatin alone was able to achieve better survival and living conditions for tumor-hosting mice. ConclusionsMGMT promoter methylation status might be a well-performed biomarker of lipid metabolism in glioblastoma. The current study can be the basis of further mechanism studies and implementation of clinical trials, and the results provide preclinical evidence of atorvastatin administration in glioblastoma, especially for MGMT unmethylated tumors.

Zexieyin formula alleviates atherosclerosis with cognitive impairment: A novel role in the treatment of comorbidities and its underlying mechanisms

Ethnopharmacological relevancyZexieyin formula (ZXYF) has been identified to have therapeutic actions of atherosclerosis (AS). It's unknown that whether ZXYF has therapeutic potential of atherosclerosis (AS) with cognitive impairment (CI) and its underlying mechanisms. Aim of the studyTo elucidate therapeutic effect of ZXYF for AS with CI as well as its underlying mechanisms in AS with CI mice model. Methods and materialsTo establish AS with CI model, we fed ApoE−/− mice with high-fat diet (HFD) for 8 weeks. Oil red O staining (ORO) and Hematoxylin-eosin staining (HE) were used to detect aortic plaque area. Morris water maze (MWM) and Y-maze were used to measure cognitive function and cognitive improvement after administration of ZXYF and atorvastatin (ATO). Network pharmacology was used to screen for potential mechanisms for improving cognitive function. Western blot was used to detect expressions of MAPK, Aβ and synaptic proteins in hippocampus. ResultsHFD caused and accelerated the AS in ApoE−/− mice, while it was easier able to produce CI than normal mice. Administration of ZXYF or ATO for 8 weeks significantly reduced aortic plaque area in ORO and HE tests, and improved cognitive abilities in MWM and Y-maze tests. Network pharmacology results showed that MAPK or synaptic proteins were highly associated with CI. HFD contributed to abnormal expressions of MAPK (pERK, pP38, pJNK), NF-kB, synaptic proteins (PSD95, synapsin1) and β-amyloid (Aβ) in hippocampus, which were all reversed by ZXYF. However, ERK and PSD95 expressions were not reversed by ATO in hippocampus. ConclusionsZXYF mitigated AS, further alleviating CI by modulating MAPK signaling, relating to synaptic proteins enhancing and Aβ protein decreasing in the hippocampus. This study firstly lit up the new clinical application of ZXYF, which might promote the use of ZXYF in AS and CI patients.

Atorvastatin ameliorated myocardial fibrosis in db/db mice by inhibiting oxidative stress and modulating macrophage polarization.

People with diabetes mellitus (DM) suffer from multiple chronic complications due to sustained hyperglycemia, especially diabetic cardiomyopathy (DCM). Oxidative stress and inflammatory cells play crucial roles in the occurrence and progression of myocardial remodeling. Macrophages polarize to two distinct phenotypes: M1 and M2, and such plasticity in phenotypes provide macrophages various biological functions. To investigate the effect of atorvastatin on cardiac function of DCM in db/db mice and its underlying mechanisms. DCM mouse models were established and randomly divided into DM, atorvastatin, and metformin groups. C57BL/6 mice were used as the control. Cardiac function was evaluated by echocardiography. Hematoxylin and eosin and Masson staining was used to examine the morphology and collagen fibers in myocardial tissues. The expression of transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), interleukin-1 β (IL-1β),M1 macrophages (iNOS+), and M2 macrophages (CD206+) were demonstrated by immunohistochemistry and immunofluorescence staining. The levels of TGF-β1, IL-1β, and TNF-α were detected by ELISA and real-time quantitative polymerase chain reaction. Malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) ac-tivities were also measured. Treatment with atorvastatin alleviated cardiac dysfunction and decreased db/db mice. The broken myocardial fibers and deposition of collagen in the myocardial interstitium were relieved especially by atorvastatin treatment. Atorvastatin also reduced the levels of serum lactate dehydrogenase, creatine kinase isoenzyme, and troponin; lowered the levels of TGF-β1, TNF-α and IL-1β in serum and myocardium; decreased the concentration of MDA and increased SOD activity in myocardium of db/db mice; inhibited M1 macrophages; and promoted M2 macrophages. Administration of atorvastatin attenuates myocardial fibrosis in db/db mice, which may be associated with the antioxidative stress and anti-inflammatory effects of atorvastatin on diabetic myocardium through modulating macrophage polarization.

Effect of atorvastatin on muscle tissues of dermatomyositis and antisynthetase syndrome patients with dyslipidemia.

In a recent study, we have shown that atorvastatin is clinically safe for dermatomyositis (DM) and antisynthetase syndrome (ASS) patients with dyslipidemia. Herein, we showed in an unprecedented way, the safety of atorvastatin on the muscular tissues of these patients. Transcriptome analysis was performed on samples of the vastus lateralis muscle obtained at baseline and after 12 weeks of atorvastatin (20 mg/day) intervention in DM or ASS patients with dyslipidemia [6DM and 5ASS received atorvastatin, and 2DM and 3ASS received placebo]. The results were analyzed considering differences in expression fold change before and after treatment. Histological and histochemical analyses were also performed. In both groups, no significant changes were observed in genes related to the mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways. Histological analysis showed a slight variability in the fiber size that was preserved after the intervention. In addition, the mosaic of muscle fibers was preserved in the internal architecture of the fibers and all histological regions. No fiber necrosis or atrophy, focal failures, subsarcolemmal accumulation, lipids, areas of fibrosis, or alterations in mitochondrial activity were observed. All muscle fibers were labeled for MHC I. Atorvastatin did not promote significant changes in the expression of genes related to mitochondrial, oxidative, insulin, lipid, and fibrogenic pathways in the muscle tissues of DM and ASS patients with dyslipidemia. Atorvastatin did not also promote histological and histochemical changes in muscle tissues. Our results reinforce the safety of the administration of atorvastatin to treat dyslipidemia in patients with DM and ASS.

Effects of Mucuna milk (Mucuna pruriens L.) on body weight and serum biochemistry in rats fed hyperlipidaemic diet

BackgroundHyperlipidemia and oxidative stress is recognized as risk factor for several diseases such as COVID-19. The aim of this study was to evaluate the effect of oral administration of Mucuna milks on body weight gain, blood lipid levels and redox status in rat model fed high fat diet.MethodsMucuna milks were produced from two varieties of Mucuna seeds. Three controls (I, II, III) made of normal rats fed with standard diet, rats fed with high fat diet and rats fed with high fat diet submitted to oral administration of atorvastatin (10 mg/kg/day). In addition, four test groups (IV, V, VI, VII) made with rats fed high fat diet and received oral administration of 20 mL of vegetable milk per day (10 mL at morning and 10 mL at afternoon).ResultsResults confirmed that rats on the high fat diet only showed an increasing of about 224% of their initial body weight, abdominal fat and a significant (p < 0.05) increases of lipid peroxidation (MDA) in liver and heart after five weeks. However, oral administration of Mucuna milk inhibit weight gain by about 66% and abdominal fat (54.53–55.60%). The reduction of LDL, VLDL, Triglycerides and Total cholesterol was remarkable in groups of rat treated with vegetable milk, about 67% reduction for dehulled Mucuna milks (DCM, DVM) and 69% reduction for whole Mucuna milks (WCM, WVM). Hyperlipidemic group rats had higher ASAT (134.17 UI/L) and ALAT (101.72 UI/L) levels, but Mucuna milks improved the ASAT and ALAT levels in rats. The reduction of MDA (70 − 50%) was related to phenolic content of Mucuna milks. significant and negative correlations was observed between catalase and MDA (r= -0.86; p = 0.05); MDA and SOD (r = − 0.60; p = 0.05).ConclusionThis study suggests that treatment with Mucuna milks have anti-hyperlipidemia properties and increased the activity of antioxidant enzymes.

Efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma.

To explore the clinical efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma. We conducted a retrospective study to analyze the clinical data of patients with chronic subdural hematoma. Patients receiving atorvastatin treatment after surgery were divided into the study group while others were divided into the control group. As the primary outcome, we compared the hematoma recurrence rate. The secondary outcomes were the remaining volume of hematoma and the activities of daily living (Barthel index) score at 3 months after discharge. A total of 53 patients were included in the study: 30 patients in the study group (n = 30) and 23 patients in the control group (n = 23). The baseline clinical data were similar in the 2 groups (P > .05). Four patients had recurrence of hematoma in the study group, while 5 patients had recurrence of hematoma in the control group [4/30 (13.3%) versus 5/23 (21.7%), P = .661] at 3 months after discharge. The mean remaining volume of hematoma was 12.10 ± 8.80 mL in the study group and 17.30 ± 9.50 mL in the control group at 3 months after discharge, respectively. The remaining volume of hematoma in the study group was less than that in the control group (P = .045).The activities of daily living score in the study group were higher than those in the control group (97.83 ± 4.48 vs 94.78 ± 5.73, P = .034) at 3 months after discharge. Atorvastatin administration after surgery barely reduce the recurrence rate of chronic subdural hematoma, however, reduced the remaining volume of hematoma and improved neurological function.

Medication-related osteonecrosis of the jaws associated with the use of bone-modifying agents: new studies

The relevance of the study is associated with the widespread use of osteomodifying agents in patients with bone metastases and osteoporosis. A serious complication associated with the use of bisphosphonates and other osteomodifying agents is known — medical osteonecrosis of the jaws, but the pathogenesis of this disease has not been fully studied. With drug-induced osteonecrosis of the jaws in oncological patients with bone metastases, therapy with osteomodifying agents is suspended, which can cause a decrease in the patient's life span. This is due to the importance of prevention, early diagnosis, and rapid treatment of patients with drug-induced osteonecosis. The aim of the work was to analyze the studies carried out in 2021—2023 on new methods of diagnosis, treatment, prevention of medical osteonecrosis of the jaws. The literature review is based on the analysis of published studies according to the PubMed electronic resource.&#x0D; The analysis of the literature data showed that bisphosphonates and other osteomodifying agents are widely used in oncology and the profile of age-related changes in the human bone system. The use, therapeutic effects and complications of therapy with osteomonefying agents are being investigated all over the world. Cone-beam computed tomography remains the "gold standard" in the diagnosis of medicamental osteonecrosis of people. Antibiotic therapy is considered as an effective method of treatment. It is proposed to use hyperbaric oxygenation, laser treatment, bone resection under fluorescence control, photodynamic therapy, introduction of a biomaterial based on tricalcium phosphate, administration of teriparatide and atorvastatin as additional treatment methods. Regular dental examinations are the most effective means of preventing drug-induced osteonecrosis. The study of pathogenesis, new methods of therapy and prevention of drug-induced osteonecrosis of the jaws remains urgent.

Effect of atorvastatin on subclinical atherosclerosis in virally-suppressed HIV-infected patients with CMV seropositivity: a randomized double-blind placebo-controlled trial.

Background: Persistent immune activation and inflammation in HIV-infection are linked to excess cardiovascular risk and other non-communicable diseases. Periodic asymptomatic CMV-reactivity in HIV infected patients over a lifetime may contribute to non-AIDS defining morbidity. Despite undetectable levels of HIV and CMV, these patients continue to have increased levels of biomarkers and immune activations. Statin administration is thought to reduce subclinical atherosclerosis by decreasing LDL-C levels. It may also add beneficial effects against CMV infection. Methods: We are conducting a double-blind placebo-controlled trial in which patients are randomized to receive either atorvastatin or placebo with a ratio of 1:1. This trial aims to study the effect of atorvastatin in statin-naive virally-suppressed HIV-infected patients with stable ART and CMV seropositivity on carotid intima media thickness (CIMT), tool that evaluates subclinical atherosclerosis. The study recruits 80 patients at HIV integrated care unit of Cipto Mangunkusumo hospital. All eligible subjects have CIMT evaluation as primary outcome, along with flow mediated vasodilatation (FMD), liver fibrosis and steatosis evaluation, fasting lipid, neurocognitive test, community periodontal index (CPI), and residual immune activation as secondary outcomes in 48 weeks. Ethics and dissemination: This study has received an ethical approval from Health Research Ethics Commitee-Universitas Indonesia and Cipto Mangunkusumo Hospital. Before joining the study, all participants fill in an informed consent form. At the end of study analysis, the trial results will be published and disseminated in peer-reviewed journals. Discussion: The main purpose of our study is to evaluate the effect of atorvastatin administration on CIMT changes in statin naïve virally suppressed HIV-infected patients with stable ART and CMV seropositivity Registration: ClinicalTrials.gov ID NCT04101136; registered on 24 September 2019.

The influence of OATP2B1 and atorvastatin on coproporphyrin isomers in rats

Coproporphyrin I (CPI) and III (CPIII) are discussed as biomarkers for organic anion transporting polypeptides (OATPs). We report on CPI and CPIII levels in wildtype, rSlco2b1-knockout, and SLCO2B1-humanized rats at baseline and after administration of atorvastatin, an inhibitor of the CPIII-specific rOATP2B1/hOATP2B1 and the CPI/CPIII-transporting rOATP1B2. OATP-inhibition by atorvastatin leads to significantly increased CPI and CPIII serum levels. However, basal CP serum levels in rSlco2b1-knockout animals were significantly lower (CPI), or unaffected (CPIII). In the presence of atorvastatin, this genotype effect was abolished. In conclusion, our results indicate an unexpected impact of OATP2B1 on CP serum levels in rats.

The influence of atorvastatin, amlodipine and ethoxidol on ubiquinol and ubiquinone endogenous plasma concentrations in patients with chronic heart failure.

Coenzyme Q10 is a key component of the mitochondrial respiratory chain and a fat-soluble endogenous antioxidant performing many vital functions in the human body. Many researchers studied the plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and the redox state (ubiquinol/ubiquinone ratio) of CoQ10 in healthy volunteers. However, these parameters in the plasma of patients with chronic heart failure (CHF) remain almost uninvestigated. The aim of this case-control study was to investigate the effect of atorvastatin, amlodipine and ethoxidol on endogenous plasma concentrations of ubiquinol, ubiquinone, total CoQ10 and its redox state in patients with CHF. The study included 62 patients with CHF divided into four groups depending on the prescribed therapy. For the quantitative determination of ubiquinol, ubiquinone, and total CoQ10 in the plasma of patients, HPLC-MS/MS was used. It was established that the endogenous plasma concentration of total CoQ10 in patients with CHF is significantly lower than in healthy volunteers, and the ratio of reduced and oxidized forms of CoQ10 is shifted towards ubiquinone. It was a statistically significant effect of drugs with different physicochemical structures and pharmacological action on the plasma concentrations of ubiquinol, ubiquinone and total CoQ10: atorvastatin administration led to a decrease in the concentration of ubiquinol (-33.3Δ%), and total CoQ10 (-15Δ%), administration of amlodipine contributed to an increase in the levels of ubiquinol (+27.7Δ%) and total CoQ10 (+18.2Δ%), and the administration of ethoxidol caused an increase in the concentration of ubiquinol (+25Δ%), ubiquinone (+17.7Δ%) and total CoQ10 (+20.2Δ%). Amlodipine is able to neutralize the negative effect of atorvastin on the redox balance of CoQ10 in patients with CHF. An additional prescription of the antioxidant ethoxidol to standard therapy for patients with CHF was substantiated. Determination of the redox state of CoQ10 in plasma can be used to diagnose and assess the degree of oxidative stress in patients with cardiovascular diseases, as well as to assess the efficacy and safety of ongoing pharmacotherapy.

A Prospective Study of the Effect and Safety of Atorvastatin on the Recurrence of Chronic Subdural Hematoma after Burr Hole Surgery.

Introduction Chronic subdural hematoma (CSDH) is a common neurosurgical condition. Recent studies showed efficacy of atorvastatin in reducing the requirement of surgical treatment. This study aimed to evaluate the efficacy and safety of atorvastatin in reducing the recurrence of CSDH after burr hole surgery. Methods This prospective study included patients with CSDH who underwent burr hole surgery. Atorvastatin at 20 mg per day was administered to all patients for 4 weeks postoperatively. The major outcome was the recurrence rate of CSDH at 8 weeks following the operation. Results Seventy-three patients who completed the 4-week course of atorvastatin were included. The mean age was 73.9 years. The most common cause of CSDH was falling. The mean hematoma volume was 106.3 mL. There was no adverse effect of atorvastatin in all of 73 patients. During the 8-week postoperative period, recurrent CSDH was found in 2 of 73 (2.7%) patients. In a comparison of the recurrence rate of CSDH between patients with use of atorvastatin from the present and previous studies (2.6-4.8%), and patients without use of atorvastatin from previous studies (9.8-19%), a marked reduction in recurrent CSDH after burr hole surgery was found in patients with use of atorvastatin. Conclusion An administration of atorvastatin of 20 mg daily for 4 weeks following burr hole surgery is safe and may be helpful in reducing the recurrence rate of CSDH after burr hole surgery.

Anti-Hyperlipidemic Effect of Fucoidan Fractions Prepared from Iceland Brown Algae Ascophyllum nodosum in an Hyperlipidemic Mice Model.

Ascophyllum nodosum, a brown algae abundantly found along the North Atlantic coast, is recognized for its high polysaccharide content. In this study, we investigated the anti-hyperlipidemic effect of fucoidans derived from A. nodosum, aiming to provide information for their potential application in anti-hyperlipidemic therapies and to explore comprehensive utilization of this Iceland brown seaweed. The crude fucoidan prepared from A. nodosum was separated using a diethylethanolamine column, resulting in two fucoidan fractions, AFC-1 and AFC-2. Both fractions were predominantly composed of fucose and xylose. AFC-1 exhibited a higher sulfate content of 27.8% compared to AFC-2 with 17.0%. AFC-2 was primarily sulfated at the hydroxy group of C2, whereas AFC-1 was sulfated at both the hydroxy groups of C2 and C4. To evaluate the anti-hyperlipidemic effect, a hyperlipidemia mouse model was established by feeding mice a high-fat diet. The effects of AFC-1, AFC-2, and the crude extract were investigated, with the drug atorvastatin used as a positive comparison. Among the different fucoidan fractions and doses, the high dose of AFC-2 administration demonstrated the most significant anti-hyperlipidemic effect across various aspects, including physiological parameters, blood glucose levels, lipid profile, histological analysis, and the activities of oxidative stress-related enzymes and lipoprotein-metabolism-related enzymes (p < 0.05 for the final body weight and p < 0.01 for the rest indicators, compared with the model group), and its effect is comparable to the atorvastatin administration. Furthermore, fucoidan administration resulted in a lower degree of loss in gut flora diversity compared to atorvastatin administration. These findings highlight the significant biomedical potential of fucoidans derived from A. nodosum as a promising therapeutic solution for hypolipidemia.

Therapeutic Effect of Atorvastatin on Interleukin-13- Induced Lung Pathology

PPurpose: Asthma is a common chronic lung disease, in which interleukin (IL)-13 is implicated as a central regulator of IgE synthesis, mucus hypersecretion, airway hyperresponsiveness (AHR), and fibrosis. This study was designed to determine the anti-inflammatory effect of atorvastatin, a widely used lipid-lowering agent, on IL-13-induced lung pathology through the modulation of macrophages. Methods: Atorvastatin (40 mg/ kg) was given to transgenic mice overexpressing IL-13 (IL-13 TG mice) and their wild type littermates by oral gavage for 2 weeks. AHR, the number of inflammatory cells in the airway, and cytokine levels in IL-13 TG mice were measured. Using the alveolar macrophage (AM) cell line CRL-2456, the direct effect of atorvastatin on macrophages activated by recombinant IL-13 was assessed. Results: Significant reduction in total leukocytes and alleviation of AHR were observed with the administration of atorvastatin in IL-13 TG mice compared to those without atorvastatin treatment (P &lt; 0.05). Atorvastatin administration resulted in the upregulation of IL-10 in the lungs of IL-13 TG mice (P &lt; 0.05). In addition, mRNA expression of connective tissue growth factor, fibronectin, and type III collagen as well as chord length enhanced by IL-13 overexpression were reduced by atorvastatin administration (P &lt; 0.05). M2 macrophage markers were decreased, while the M1 macrophage marker was increased upon atorvastatin treatment (P &lt; 0.05). Administration of atorvastatin resulted in improved removal of apoptotic cells (P &lt; 0.05). Conclusion: The results of this study reveal the potential of atorvastatin as an effective anti-asthmatic agent by reducing IL-13-induced lung inflammation via the modulation of macrophage polarization.

Effects of Citicoline and Atorvastatin Administration on the Regenerative Capacity of the Distal Segment of the Transected Sciatic Nerve in Conditions of Delayed Nerve Repair

Introduction: The reduced organ function following delayed nerve repair highlights the need for pharmacological interventions. In this regard, many chemical agents have been administered after nerve injury; however, their functional outcomes are not satisfying yet. The present study aimed to evaluate the effects of the administration of citicoline and atorvastatin on the regenerative capacity of the distal end of the transected sciatic nerve throughout a delayed nerve repair period. Method: The sciatic nerve of male rats (250-300 g) was transected, and the animals were intraperitoneally administrated citicoline (200 mg/kg, n=5), atorvastatin (5 mg/kg, n=5), citicoline + atorvastatin, and vehicles (control groups 1 and 2, n=5) for one month. In the sham group (n=5), the sciatic nerve was only exposed. After one month, the transected nerve was repaired. Fourteen weeks after surgical repair, morphometric and electron microscopic evaluations were performed on the nerve. Results: In the present study, improvement in the structural (fiber diameter, axon diameter, and myelin thickness, etc.) and ultrastructural (degree of myelin destruction) indices of the distal segment of the nerve was observed in the citicoline and atorvastatin groups compared to the control groups (P&lt; 0.01). In addition, the nerve structural and ultrastructural indices in the citicoline + atorvastatin group were better than each citicoline and atorvastatin group. Conclusion: The results of this study showed that the administration of citicoline and atorvastatin leads to maintaining the regeneration capacity of the distal part of the nerve in the condition of delayed nerve repair

The ABCB1 C3435T Polymorphism is Associated with Triglyceride Reduction in Atorvastatin-treated Uygur Patients with Coronary Heart Disease and Dyslipidemia: An Observational Study.

The morbidity of coronary heart disease (CHD) and dyslipidemia in the Uygur population of Xinjiang is higher than the national average. Interindividual variability of the response to atorvastatin is a major clinical problem; generally, statins shed less impressive benefits for females than males. Nevertheless, it is unclear whether ABCB1 genes and sex modify the efficacy of atorvastatin in Uygur patients. To determine the impact of ABCB1 gene polymorphisms on the therapeutic response to atorvastatin in a Uygur population with dyslipidemia. Patients with dyslipidemia were treated with 20 mg/d or 40 mg/d atorvastatin for two to six months. TC, LDL-C, HDL-C, TG, APOB, APOE, LP(a), and APOA1 levels were measured before and after atorvastatin administration. We performed genotyping of ABCB1 C3435T and G2677T variants using hybridization sequencing. The association of variants between the percentage of change in TG levels was examined using multiple linear regression analysis. We enrolled 193 Uygur patients. Atorvastatin reduced TG, LDL-C, TC, APOB, and APOE levels (P < 0.05), whereas LP(a) and APOA1 levels increased (P < 0.05). In multiple linear regression analysis, baseline TG level (beta 0.204; 95% confidence interval (CI): 1.980-10.493; P = 0.004) and TT genotype of ABCB1 C3435T (beta 0.162; 95% CI: 2.517-23.406; P = 0.023) predicted TG reduction with atorvastatin therapy in overall patients. Baseline TG level (beta 0.346; 95% CI: 4.374 -13.34; P < 0.001) with the TT genotype of ABCB1 C3435T (beta 0.401; 95% CI: 4.053-28.356; P = 0.021) was associated with a significant reduction in TG levels in men. Only baseline TG level predicted TG reduction within six months of atorvastatin therapy for females (beta 0.61; 95% CI: 3.204-20.557; P = 0.041). In patients with the ABCB1 C3435T TT genotype, atorvastatin more effectively lowered TG than other polymorphisms. This investigation may provide insights into effective individualized therapies for CHD and dyslipidemia in the Uygur population.

Rivaroxaban Combined with Atorvastatin Inhibits Acute Pulmonary Embolism by Promoting the Expression of NRF2/NQO1.

Atorvastatin and direct oral factor Xa inhibitors (for instance, rivaroxaban) are co-administrated in patients with atrial fibrillation. However, no studies have been conducted on the function of these two agents in acute pulmonary embolism (APE). Therefore, we investigated the effects of rivaroxaban + atorvastatin in rats with APE and explored the underlying mechanisms. Patients with APE were enrolled, and rats with APE were generated for different regimens. The mean pulmonary arterial pressure (mPAP), heart rate, and PaO2 of APE patients and rats were measured. The plasma levels of oxidative stress- and inflammation-related factors were measured, and the expression of platelet activation markers (CD63 and CD62P) was detected. The proteins targeted by rivaroxaban and atorvastatin, the targets associated with APE, and the genes aberrantly expressed in rats with APE were intersected to obtain candidate factors. Rivaroxaban + atorvastatin reduced mPAP and increased PaO2 in patients and rats with APE. Rivaroxaban + atorvastatin repressed oxidative stress, inflammatory levels, and platelet activation during APE. NRF2 and NQO1 were increased in the lung of rats treated with rivaroxaban + atorvastatin. The therapeutic effect of the combination on APE rats was suppressed after NRF2 downregulation. NRF2 promoted the NQO1 transcription. NQO1 eliminated the inhibitory effect of sh-NRF2 on the combined therapy. The alleviating effect of rivaroxaban + atorvastatin administration against APE correlates with NRF2/NQO1 expression.

#5848 ROLE OF STATINS IN THE CONTRAST-INDUCED ACUTE KIDNEY INJURY PREVENTION AFTER COMPUTED TOMOGRAPHY WITH CONTRAST MEDIA

Abstract Background and Aims Contrast-induced acute kidney injury (CI-AKI) is a serious complication of the use of iodinated contrast media (CM). A number of researches have shown that statins have a protective role in the prevention of CI-AKI due to their pleiotropic effects. The aim of the study was to assess the influence of statins on the incidence of CI-AKI after intravenous CM administration. Method A randomized controlled open-label prospective study was conducted. Statin naive patients with cardiovascular diseases referred for contrast-enhanced computed tomography (CT) were included. Exclusion criteria were the use of statins and chronic kidney disease (CKD) stages 4-5. Acute kidney injury was defined as an increase in serum creatinine level by more than 44 μmol/L (0.5 mg/dL) or 25% from baseline within 48 hours after CM administration according to KDIGO guidelines. Glomerular filtration rate was calculated using the CKD-EPI formula. Overall, 181 patients were included in the study and divided into two groups. The first group (120 people) received high doses of atorvastatin (80mg or 40mg) 24 hours after and before the CM administration, while the second group (61 people), the control group, did not receive any statin therapy. Low-osmolar solutions in an amount of 100 ml were used. All patients were given intravenous hydration with saline before the study and 24 hours later. The statistical analysis was done using IBM SPSS Statistics v26.0. Results The patients in both groups did not significantly differ in age, BMI, coexisting conditions, and medications taken (Table 1). Both groups showed an increase in average creatinine levels after CT with intravenous CM administration, however, in the group of patients receiving high doses of statins, the average level increased less, p = 0.092 (Table 2). AKI developed in 12 individuals (6.7%), 9 of them were in the control group, and 3 were in the group receiving high doses of statins, p = 0.003. The chances of AKI development in the group receiving high doses of statins were 6.95 times lower compared to the control group (OR = 6.05, 95% CI: 1.7-21.5). Most of the patients had preserved kidney function and did not suffer from diabetes mellitus. There were statistically significantly more patients with preserved kidney function in the statin group, p = 0,007, OR: 2,374 (CI 95% 1,258 - 4,479), and fewer patients with CKD 3a stage, p = 0,05, OR: 0,406 (CI 95% 0,195 – 0,844). Conclusion Despite the presence of patients at risk, the incidence of CI-AKI was 6.7%, possibly due to additional prevention of this complication with intravenous saline before and after administration of the CM. In this trial, we observed that periprocedural administration of atorvastatin in high doses for a short duration, reduced the incidence of CI-AKI.