Dysregulation of autophagy activation induced by atorvastatin contributes to new-onset diabetes mellitus in western diet-fed mice.

BACKGROUND AND AIMS: The incidence of statin-induced new-onset diabetes (NOD) is increasing but its underlying mechanisms remain unclear. We aimed to investigate the effects of various doses of atorvastatin (ATO)-induced autophagy on the development of NOD. METHODS AND RESULTS: The isolated rat islets and MIN6 cells-treated with ATO, exhibited impaired glucose-stimulated insulin secretion, reduced insulin content, and induced apoptosis. Additionally, autophagy was induced at all doses (in vitro: 5, 10, 20 µM; in vivo: 10, 15, 20 mg/kg) in ATO-treated MIN6 cells or western diet (WD)-fed mice. In contrast to normal glucose-tolerant mice administered a low-dose (10 mg/kg) ATO, those treated with high-doses (15 or 20 mg/kg) exhibited impaired glucose tolerance. Furthermore, high-dose ATO-treated mice showed decreased ß-cell mass and increased apoptosis compared to that of vehicle-treated mice. We also observed that the number of vesicophagous cells in the pancreas of 20 mg/kg ATO-treated WD-fed mice was higher than in vehicle-treated WD-fed mice. Inhibiting autophagy using 3-methyladenine (3-MA) and siAtg5 improved glucose tolerance in vivo and in vitro by preventing apoptotic ß-cell death and restoring insulin granules. CONCLUSION: These results indicate that high doses of ATO induced hyperactivated autophagy in pancreatic cells, leading to impaired insulin storage, decreased cell viability, and reduced functional cell mass, ultimately resulting in NOD development.

Comparison of the efficacy and safety of Shanhuang Jiangzhi tablets and atorvastatin in the treatment of patients with hyperlipidaemia.

OBJECTIVES: To compare the efficacy and safety of Shanhuang Jiangzhi tablets and atorvastatin in reducing blood lipid levels. METHODS: Patients with hyperlipidaemia admitted to the cardiac centre between January 2019 and December 2020 were included in the study. A total of 1063 patients with hyperlipidaemia took either Shanhuang Jiangzhi tablets (n = 372) or atorvastatin (n = 691) and met the inclusion and exclusion criteria. Clinical data, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol, were retrospectively evaluated after propensity score matching (PSM) analysis. The adverse events were also recorded during the therapy process. RESULTS: Following PSM analysis, both groups were well matched across all parameters. Compared with the baseline, Shanhuang Jiangzhi tablets had greater effects on TC, TG and LDL-C, and the difference was statistically significant (p < 0.001). Furthermore, the results showed that Shanhuang Jiangzhi tablets are similar to atorvastatin in reducing TC and LDL-C, and all p-values were > 0.05. However, the decrease of TG was greater in the Shanhuang Jiangzhi group (p < 0.001). Clinical adverse reactions of Shanhuang Jiangzhi tablets are rare and have no statistical significance compared with atorvastatin (p = 0.682). CONCLUSIONS: Shanhuang Jiangzhi tablets have a higher hypotriglyceridaemic performance than atorvastatin and an equivalent ability to lower TC and LDL-C. In addition, Shanhuang Jiangzhi tablets are a low-risk option for lowering blood lipids.

Differential Pharmacokinetic Interplay of Atorvastatin on Lacosamide and Levetiracetam on Experimental Convulsions in Mice.

BACKGROUND: The beneficial effects of statins, other than their hypocholesterolemia role, have been well documented, however, their use as an adjuvant drug with other antiseizure drugs, in the treatment of epilepsy is poorly understood. OBJECTIVE: This study aimed to investigate the symbiotic effect of ATOR along with either lacosamide (LACO) or levetiracetam (LEVE) on experimentally induced epilepsy (Maximal electro-shock-MES or pentylenetetrazol- PTZ) in mice models. METHODS: Conventional elevated-maze (EPM) and rotarod methods were performed to observe the behavioral effects. RESULTS: In both the animal models, we found that co-administration of ATOR along with LACO showed a significant reduction in hind-limb extension (HLE) and clonic convulsion (CC) responses, respectively, but not in the ATOR+LEVE treated group. Intriguingly, comparable Straub tail response and myoclonic convulsion as the diazepam (DIA) group were observed only in the ATOR+LACO treated group. Moreover, a significant muscle-grip strength was observed in both groups. Also, pharmacokinetic analysis has indicated that the mean plasma concentration of ATOR peaked at 2nd hr in the presence of LACO but marginally peaked in the presence of LEVE. An Insilico study has revealed that ATOR has a higher binding affinity toward neuronal sodium channels. CONCLUSION: This study has demonstrated that the plasma concentration of ATOR was potentiated in the presence of LACO, but not in the presence of LEVE and it has provided significant protection against both the electro and chemo-convulsive models in mice. This could be due to the symbiotic pharmacokinetic interplay of ATOR with LACO, and possibly, this interplay may interfere with sodium channel conductance.

[Efficacy and safety of atorvastatin in major cardiovascular events: Meta-analysis]. / Eficacia y seguridad de la atorvastatina en eventos cardiovasculares mayores: metaanálisis.

Introduction: Atorvastatin has been used in the management of dyslipidemia and little is known about the efficacy and safety of high-dose atorvastatin administration for secondary prevention of Major Cardiovascular Events (MACE). Objective: To evaluate the impact of high-dose atorvastatin on secondary prevention of MACE and adverse events. Material and methods: A systematic review and meta-analysis of Pubmed, Embase, Bireme and Cochrane Library Plus databases was performed, with a time scope from 1990 to July 2022. Six randomized clinical trials were included with a total of 29,333 patients who were treated with 80 mg, 10 mg or placebo doses of Atorvastatin where the main outcomes evaluated were Major Cardiovascular Events (MACE), mortality and treatment safety. Results: In the comparative study between the use of Atorvastatin 80 mg and other therapies, a relative risk (RR) of 0.8 (95%CI 0.69-0.92) was found, representing a 20% reduction in risk (RRR) and a number needed to treat (NNT) of 30-55. In the analysis of adverse effects, an RR of 2.37 (95% CI 0.86-6.53) and a number needed to harm (NNH) of 14-19 were observed. The use of 80 mg atorvastatin is associated with similar adverse events at lower doses. Conclusions: The use of atorvastatin 80 mg is effective in the secondary prevention of Major Cardiovascular Event (MACE). The drug has adverse events that should be taken into account in secondary prevention.

Introducción: la atorvastatina ha sido usada en el manejo de la dislipidemia y se conoce poco sobre la eficacia y seguridad de la administración de atorvastatina en altas dosis para la prevención secundaria de eventos cardiovasculares mayores (MACE). Objetivo: evaluar el impacto de altas dosis de atorvastatina en la prevención secundaria de MACE y eventos adversos. Material y métodos: se realizó una revisión sistemática y un metaanálisis de las bases de datos Pubmed, Embase, Bireme y Cochrane Library Plus, con un alcance temporal de 1990 a julio de 2022. Se incluyeron seis ensayos clínicos aleatorios con un total de 29,333 pacientes que fueron tratados con dosis de 80 mg, 10 mg o placebo de Atorvastatina donde los resultados principales evaluados fueron los eventos cardiovasculares mayores (MACE), la mortalidad y la seguridad del tratamiento. Resultados: en el estudio comparativo entre el uso de Atorvastatina de 80 mg y otras terapias, se encontró un riesgo relativo (RR) de 0.8 (IC95%: 0.69-0.92), lo que representa una reducción del 20% en el riesgo (RRR) y un número necesario a tratar (NNT) de 30 a 55. En el análisis de los efectos adversos, se observó un RR de 2.37 (IC95%: 0.86-6.53) y un número necesario a dañar (NNH) de 14 a 19. El uso de atorvastatina de 80 mg se asocia con eventos adversos similares a dosis menores. Conclusiones: el uso de atorvastatina de 80 mg es efectivo en la prevención secundaria de evento cardiovascular mayor (MACE). El medicamento tiene eventos adversos que deben de tomarse en cuenta en la prevención secundaria.

The clinical application of atorvastatin in patients with small-cell lung cancer with dyslipidemia.

BACKGROUND: Various experimental studies demonstrated that atorvastatin exerted additive effects with anticancer drugs to impair tumor growth, delay relapse, and prolong survival time in lung cancer. However, it is indistinct whether there are survival benefits of atorvastatin in the treatment of small-cell lung cancer (SCLC) patients with dyslipidemia. Therefore, this study aimed to evaluate the efficacy and safety of atorvastatin plus first-line standard chemotherapy in SCLC combined dyslipidemia. METHODS: This was a retrospective analysis of 91 eligible SCLC patients with dyslipidemia registered at the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from October 2018 to October 2022. SCLC patients with confirmed dyslipidemia were assigned to the treatment group to receive atorvastatin plus first-line standard chemotherapy (n = 45) or to the control group to accept chemotherapy (n = 46) until disease progression or unmanageable toxicity occurred. The clinicopathological parameters and survival data were collected and analyzed. Univariate and multivariate analyses were performed to investigate the prognostic significance of SCLC. The median progression-free survival (mPFS) was considered to be the pivotal symbol as the primary endpoint. The second endpoints were recognized as the median overall survival (mOS) and toxicity. RESULTS: In the total of 91 enrolled patients, the curative effect can be evaluated in all patients. Research results showed that atorvastatin added to first-line standard chemotherapy was associated with a significant improvement in survival (mPFS: 7.4 vs 6.8 months, P = 0.031; mOS: 14.7 vs 13.2 months, P = 0.002). CONCLUSION: Atorvastatin added to first-line standard chemotherapy achieved prospective efficacy and manageable safety in SCLC combined dyslipidemia.

Effect of dietary inclusion of atorvastatin, garlic, and dill on growth performance, antioxidant defense, gut, and cardio-pulmonary function, and lipogenesis in broiler chickens.

In the present study, we evaluated the antihyperlipidemic and antioxidant effects of garlic and dill in comparison with atorvastatin to combat lipogenesis in broiler chickens. A total of 400 1-day-old chicks (Ross 308 strain) were randomly distributed into four experimental diets. Dietary treatments included a control diet, the control diet plus atorvastatin at 20 mg/kg, the control diet plus garlic dry powder (GDP) at 7.5 g/kg, and the control diet plus dill dry powder (DDP) at 7.5 g/kg. Chicks were maintained on experimental diets for 42 days under the recommended environmental conditions set out by the strain management manual. The results showed that weight gain, feed conversion ratio (FCR), and duodenal, jejunal, and ileal dimensions of villi (height, width, and the surface absorptive area) were improved by in-feed atorvastatin, GDP, or DDP when compared to the control (P < 0.05). The inclusion of atorvastatin or phytobiotic products increased circulatory levels of nitric oxide (NO) but decreased circulatory levels of malondialdehyde (MDA), triacylglycerol (TAG), and low-density lipoproteins cholesterol (LDL), with concomitant reductions in the T, R, and S waves amplitudes in the Lead 2 electrocardiogram (ECG) (P < 0.05). Dietary supplements caused an up-regulation of inducible nitric oxide synthase (iNOS), superoxide dismutase 1 (SOD1), and glutathione peroxidase (GPX) but reduced the expression of key hepatic lipogenic enzymes (fatty acid synthase (FAS) and hydroxy-methylglutaryl-CoA reductase (HMGCR) (P < 0.05). In conclusion, feed supplementation with atorvastatin, GDP, or DDP suppressed lipogenesis, enhanced antioxidant response, and improved gut and cardio-pulmonary function in broiler chicks subjected to hypobaric hypoxia.

Formulation, and optimization of transdermal Atorvastatin Calcium-Loaded Ultra-flexible vesicles; ameliorates poloxamer 407-caused dyslipidemia.

Atorvastatin calcium (AC), a cholesterol-lowering medication, has limited oral bioavailability (14 %) and adverse impacts on the gastrointestinal tract (GIT), liver, and muscle. So, in an effort to improve the poor availability and overcome the hepatotoxicity complications attendant to peroral AC administration, transdermal transfersomal gel (AC-TFG) was developed as a convenient alternative delivery technique. The impact of utilizing an edge activator (EA) and varying the phosphatidylcholine (PC): EA molar ratio on the physico-chemical characteristics of the vesicles was optimized through a Quality by Design (QbD) strategy. The optimal transdermal AC-TFG was tested in an ex-vivo permeation study employing full-thickness rat skin, Franz cell experiments, an in-vivo pharmacokinetics and pharmacodynamics (PK/PD) evaluation, and a comparison to oral AC using poloxamer-induced dyslipidemic Wister rats. The optimized AC-loaded TF nanovesicles predicted by the 23-factorial design strategy had a good correlation with the measured vesicle diameter of 71.72 ± 1.159 nm, encapsulation efficiency of 89.13 ± 0.125 %, and cumulative drug release of 88.92 ± 3.78 % over 24 h. Ex-vivo data revealed that AC-TF outperformed a free drug in terms of permeation. The pharmacokinetic parameters of optimized AC-TFG demonstrated 2.5- and 13.3-fold significant improvements in bioavailability in comparison to oral AC suspension (AC-OS) and traditional gel (AC-TG), respectively. The transdermal vesicular technique preserved the antihyperlipidemic activity of AC-OS without increasing hepatic markers. Such enhancement was proven histologically by preventing the hepatocellular harm inflicted by statins. The results showed that the transdermal vesicular system is a safe alternative way to treat dyslipidemia with AC, especially when given over a long period of time.

Anti-Atherogenic Protection by Oligomeric Proanthocyanidins via Regulating Collagen Crosslinking Against CC Diet-Induced Atherosclerosis in Rats.

The synthesis of collagen and its turnover remained as critical determinants for the progression of atherosclerosis. During this condition, proteases secreted by SMCs and foam cells in the necrotic core degrade collagen. Growing evidences demonstrated that consumption of antioxidant rich diet is highly associated with a reduced risk of atherosclerosis. Oligomeric proanthocyanidins (OPC) have been proved to possess promising antioxidant, anti-inflammatory and cardioprotective activity, based on our previous studies. The present study aims to investigate the efficacy of OPC isolated from Crataegus oxyacantha berries as a natural collagen crosslinker and anti-atherogenic agent. Spectral studies like FTIR, ultraviolet and circular dichroism analysis confirmed the in vitro crosslinking ability of OPC with rat tail collagen when compared to the standard epigallocatechin gallate. The administration of cholesterol:cholic acid (CC) diet induces proteases-mediated collagen degradation that could result in plaque instability. Further, the CC diet fed rats showed significantly increased levels of total cholesterol and triacylglycerols which, in turn, increases the activities of collagen degrading proteases-MMPs (MMP 1, 2 and 9) and Cathepsin S and D. Upon OPC treatment, marked reduction in the lipid content, activation of proteases with concomitant increase in the mRNA levels of collagen Type I and Type III as similar to atorvastatin treatment were observed .Thus, OPC supplementation may contribute to the prevention of atherosclerotic plaque instability by acting as a natural crosslinker of collagen.

Additive Therapy of Plasmodium berghei-Induced Experimental Cerebral Malaria via Dihydroartemisinin Combined with Rapamycin and Atorvastatin.

Cerebral malaria (CM), caused by Plasmodium falciparum, is the primary cause of death from severe malaria. Even after immediate parenteral therapy with antimalarial drugs, the mortality rate remains 15 to 25%. Currently, no effective therapeutic agents are available for the radical treatment of CM. Thus, further in-depth explorations of adjuvant therapies in combination with antimalarial drugs are urgently needed. The experimental cerebral malaria (ECM) model was established by infecting C57BL/6 mice with Plasmodium berghei ANKA. Subsequently, infected mice were continuously treated with dihydroartemisinin (DHA) in combination with rapamycin (RAP) and atorvastatin (AVA) for 5 days at different time points, including day 0, day 3, and day 6 postinfection (p.i.). Treatment efficacy was evaluated by comparing behavioral scores, body weight, parasitemia, survival rate, blood-brain barrier (BBB) integrity, and histopathology. The optimal combination therapy of DHA, RAP, and AVA on day 3 p.i. was selected for ECM. This strategy significantly improved survival rate, reduced parasitemia, improved the rapid murine coma and behavioral scale scores and permeability of the BBB, attenuated cerebrovascular and hepatic central venous obstruction and hemozoin deposition in the liver, and decreased the red pulp area of the spleen, which effectively ameliorated neurological damage in ECM. It also improved histopathology and neurological damage caused by ECM. In this study, the optimal therapeutic strategy for ECM was selected, which is expected to be a potential therapy for human CM. IMPORTANCE Although artemisinin-based combination therapies (ACTs) have greatly improved the clinical outcome of cerebral malaria (CM) as a fatal disease that can permanently disable a significant proportion of children even if they survive, new treatment options are needed as Plasmodium falciparum develops resistance to antimalarial drugs. Recent reports suggest that basal treatment with artemisinin derivatives often fails to protect against cell death, neurological damage, and cognitive deficits. In this study, the combination of dihydroartemisinin with rapamycin and atorvastatin improved the current antimalarial outcomes by overcoming the limitations of current antimalarials for CM morbidity and neurological sequelae. This combination offers a new adjunctive treatment for the clinical treatment of human CM in susceptible populations, including children under 5 years old and pregnant women.

Association of octacosanol supplementation with redox status in patients on chronic statin therapy.

Background: The uneven lipid-lowering statin effects and statin intolerance raise interest regarding the involvement of coadministration of statins and dietary supplements. This study aimed to evaluate the effects of octacosanol supplementation on markers of redox status in cardiovascular patients on chronic atorvastatin therapy. Methods: A double-blind, randomized, placebo-controlled, single-centre study was conducted. Redox status homeostasis parameters [i.e., advanced oxidation protein products (AOPP), pro-oxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase activity (SOD), total protein sulfhydryl (SHgroups), and paraoxonase 1 (PO N 1) activity] were assessed in 81 patients. According to favorable changes in lipid profile, patients were classified into two groups: responders (n = 35) and non-responders (n = 46), and followed for 13 weeks. A principal component analysis (PCA) was applied to explore the effect of octacosanol supplementation and the relationship between investigated parameters as predictors of responders' and non-responders' status. Results: Significant decrease in Oxy-score value was found at the endpoint compared to baseline in responders' group (21.0 (13.4-25.5) versus 15.1 (12.4-18.0); P < 0.01). PCA analysis extracted 4 significant factors in the both groups, whereas extracted factors containing "octacosanol status" variable explained 14.7% and 11.5% of the variance in responders' and non-responders' subgroups, respectively. Conclusions: Octacosanol supplementation leads to an improvement of lipid profile and markers of redox status in responders' group. New studies are needed to validate our results in order to find the best approach for personalized supplementation as a useful adjunct to standard statin therapy.

Atorvastatin attenuates allergic inflammation by blocking prostaglandin biosynthesis in rats with allergic rhinitis.

BACKGROUND: Prostaglandins (PGs) are bioactive lipid mediators derived from the nuclear and plasma membranes via the cyclooxygenase (COX) pathway of arachidonic acid (AA) metabolism. PGs bridge the interactions between various immunomodulatory cells in allergic rhinitis (AR) and are considered key players in regulating pro-inflammatory and anti-inflammatory responses. AA conversion to PGs involves rate-limiting enzymes that may be blocked by statins. The mechanisms by which statins regulate these enzymes in AR remain unclear. We investigated the effects of oral atorvastatin on PGs production in AR. METHODS: An ovalbumin-induced AR rat model was constructed and the changes in nasal symptom score and nasal mucosa histopathological characteristics of AR rats under different atorvastatin doses were assessed. qRT-PCR, western blotting, and immunofluorescence were used to detect the mRNA and protein expression levels of rate-limiting enzymes and downstream molecules of AA metabolism in the nasal mucosa and liver. RESULTS: Oral atorvastatin significantly alleviated symptoms and eosinophil infiltration in the nasal mucosa, inhibited goblet cell hyperplasia and mast cell recruitment, and decreased mucus secretion in AR rats. Increasing atorvastatin dose increased the anti-inflammatory effects. High-dose atorvastatin inhibited upregulation of the inflammatory mediator PGD2 in the nasal mucosa of AR rats. Compared to the control group, the mRNA and protein expression of the rate-limiting enzymes COX-2, PGDS, and PGES in AA metabolism in the AR group were upregulated but downregulated after the oral administration of high-dose atorvastatin. Atorvastatin also showed dose-dependent inhibition of ERK1/2 and downstream NF-κB phosphorylation in the nasal mucosa and liver of AR rats. CONCLUSIONS: Atorvastatin inhibited allergic inflammation and attenuated AR nasal symptoms by downregulating PGD2 and rate-limiting enzyme expression in PGD2 biosynthesis, possibly by blocking the RAS/ERK/NF-κB signaling pathway.

pH-Responsive Selenium Nanoplatform for Highly Efficient Cancer Starvation Therapy by Atorvastatin Delivery.

Recently, starvation-inducing nutrient deprivation has been regarded as a promising strategy for tumor suppression. As a first-line lipid-lowering drug, atorvastatin (ATV) significantly reduces caloric intake, suggesting its potential in starvation therapy for suppressing tumors. Accordingly, we developed a novel starvation therapy agent (HA-Se-ATV) in this study to suppress tumor growth by using hyaluronic acid (HA)-conjugated chitosan polymer-coated nano-selenium (Se) for loading ATV. HA-Se-ATV targets cancer cells, following which it effectively accumulates in the tumor tissue. The HA-Se-ATV nanoplatform was then activated by inducing a weakly acidic tumor microenvironment and subsequently releasing ATV. ATV and Se synergistically downregulate the levels of cellular adenosine triphosphate while inhibiting the expression of thioredoxin reductase 1. Consequently, the starvation-stress reaction of cancer cells is significantly elevated, leading to cancer cell death. Furthermore, the in vivo results indicate that HA-Se-ATV effectively suppresses tumor growth with a low level of toxicity, demonstrating its great potential for clinical translation.

Atorvastatin remodels lipid distribution between liver and adipose tissues through blocking lipoprotein efflux in fish.

The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However, studies on the role of statins in cholesterol metabolism in fish are currently limited. The present study evaluated the effects of statins on cholesterol metabolism in fish. Nile tilapia (Oreochromis niloticus) were fed on control diets supplemented with three atorvastatin levels (0, 12, and 24 mg/kg diet, ATV0, ATV12, and ATV24, respectively) for 4 wk. Intriguingly, the results showed that both atorvastatin treatments increased hepatic cholesterol and triglyceride contents mainly through inhibiting bile acid synthesis and efflux, and compensatorily enhancing cholesterol synthesis in fish liver (P < 0.05). Moreover, atorvastatin treatment significantly inhibited hepatic very-low-density lipoprotein (VLDL) assembly and thus decreased serum VLDL content (P < 0.05). However, fish treated with atorvastatin significantly reduced cholesterol and triglycerides contents in adipose tissue (P < 0.05). Further molecular analysis showed that atorvastatin treatment promoted cholesterol synthesis and lipogenesis pathways, but inhibited lipid catabolism and low-density lipoprotein (LDL) uptake in the adipose tissue of fish (P < 0.05). In general, atorvastatin induced the remodeling of lipid distribution between liver and adipose tissues through blocking VLDL efflux from the liver to adipose tissue of fish. Our results provide a novel regulatory pattern of cholesterol metabolism response caused by atorvastatin in fish, which is distinct from mammals: cholesterol inhibition by atorvastatin activates hepatic cholesterol synthesis and inhibits its efflux to maintain cholesterol homeostasis, consequently reduces cholesterol storage in fish adipose tissue.

Craniocervical Manual Lymphatic Drainage Increases the Efficiency of Atorvastatin-Based Treatment of Chronic Subdural Hematoma.

The objective of this study is to explore whether craniocervical manual lymphatic drainage (cMLD) can promote hematoma absorption and increase the efficiency of atorvastatin-based conservative treatment in chronic subdural hematoma (CSDH) patients. All CSDH patients treated with atorvastatin-based therapy between October 2020 and February 2022 in our department were retrospectively screened for enrollment. The patients were divided into the control and cMLD groups according to whether cMLD was performed. Head CT or MR images in both groups were obtained before the treatment and 2 weeks and 4 weeks after the treatment. MR images of the deep cervical lymphatic nodes (dCLNs) in 23 patients were obtained in the cMLD group before and approximately 2 weeks after treatment. The volumes of the dCLNs and hematoma were calculated. The primary outcomes are the differences in hematoma volume reduction after 4 weeks of treatment. The secondary outcomes were (1) the differences in hematoma volume reduction between the patients in these two groups in the 2nd week, (2) the dCLN volume change in the cMLD group before and after 2 weeks of treatment, and (3) the percentage of patients who transitioned to surgery because of failure to the conservative treatment. A total of 106 consecutive patients were enrolled in this study for analysis; 54 patients received atorvastatin-based treatment (control group), and 52 were treated with both atorvastatin-based treatment and cMLD (cMLD group). At baseline, the mean hematoma volume was 76.53 ± 42.97 ml in the control group and 88.57 ± 49.01 ml in the cMLD group (p = 0.181). In the 4th week, the absolute number of hematoma reductions (20.79 ± 34.73 ml vs. 37.28 ± 28.24 ml, p = 0.009) and percentage of hematoma reductions (22.58% ± 60.01% vs. 46.43% ± 30.12%, p = 0.012) in the cMLD group were greater than those in the control group. After 2 weeks of treatment, the absolute number of hematoma reductions showed no difference in the two groups, while the percentage of hematoma reduction was higher in the cMLD group (18.18% ± 24.61% vs. 2.08% ± 25.72%, p = 0.001). One patient in cMLD and 8 patients in the control group were transitioned to receive surgical treatment. The dCLN volumes in 23 experimental patients increased significantly after 2 weeks of treatment in the cMLD group (p = 0.032). There were no severe side effects that needed to be reported. Combined with atorvastatin-based therapy, cMLD can promote hematoma absorption and decrease the surgery rate, which provides a new therapeutic strategy for CSDH.

Effects of different doses of simvastatin and atorvastatin combined with trimetazidine on blood lipids and cardiac function in patients with chronic heart failure / 中国基层医药

Objective:To investigate the effects of different doses of simvastatin and atorvastatin combined with trimetazidine on blood lipids and cardiac function in patients with chronic heart failure.Methods:A total of 100 patients with chronic heart failure who received treatment in Jinan Second People's Hospital from September 2019 to August 2021 were included in this study. These patients were divided into three groups according to different treatment methods: group A ( n = 33), group B ( n = 33), and group C ( n = 34). Group A was treated with a conventional dose of simvastatin combined with trimetazidine. Group B was treated with a high dose of simvastatin combined with trimetazidine. Group C was treated with atorvastatin combined with trimetazidine. All patients were treated for 6 months. Cardiac function, blood lipids, inflammatory factors, and excellent and good rates of therapeutic effects post-treatment were compared between the three groups. The adverse events during the treatment were recorded. Results:There were no significant differences in blood lipids, cardiac function, inflammatory factors, and excellent and good rates of therapeutic effects between the two groups (all P > 0.05). After 6 months of treatment, high-density lipoprotein cholesterol [(1.99 ± 0.25) mmol/L, (2.01 ± 0.16) mmol/L] and left ventricular ejection fraction [(51.29 ± 4.15)%, (51.37 ± 4.44)%] in groups B and C were significantly higher than those in group A [(1.52 ± 0.16) mmol/L, (42.28 ± 4.86)%, t = 9.10, 6.24; 8.10, 11.38, all P < 0.05). Caspase-1 [(42.33 ± 3.19) ng/L, (41.87 ± 3.55) ng/L], interleukin-18 [(54.55 ± 4.39) ng/L, (53.98 ± 4.45) ng/L], left ventricular end-systolic diameter [(35.13 ± 2.13) mm, (35.68 ± 2.46) mm], left ventricular end-diastolic diameter [(44.39 ± 3.65) mm, (44.42 ± 3.32) mm], low-density lipoprotein cholesterol [(2.69 ± 0.39) mmol/L, (2.57 ± 0.13) mmol/L], total cholesterol [(3.79 ± 0.13 ) mmol/L, (3.56 ± 0.69) mmol/L], triacylglycerol [(1.12 ± 0.05) mmol/L, (1.10 ± 0.07) mmol/L] levels in groups B and C were significantly lower than those in group A [(68.41 ±10.23) ng/L, (88.37 ± 6.65) ng/L, (42.63 ± 3.13) mm, (51.68 ± 5.42) mm, (3.13 ± 0.11) mmol/L, (4.21 ± 0.11) mmol/L, (1.51 ± 0.11) mmol/L, t = -13.98, -24.38, -14.27, -24.95, -6.41, -5.64, -8.00, -10.12, -14.17, -18.54, -12.53, -19.01, -5.35, -18.26, all P < 0.05]. 6-minute walking distances [(352.19 ± 25.4) m, (351.74 ± 24.29) m] in groups B and C were significantly longer than that in group A [(319.71 ± 21.11) m, t = 6.63, 5.75, both P < 0.05). The excellent and good rates at 3 and 6 months after surgery in group B was significantly higher than that in group A ( χ2 = 4.00, 4.16, both P < 0.05), but the incidence of adverse reactions in group B [18.18% (6/33)] was significantly higher than 3.03% (1/33) in group A and 2.94% (1/34) in group C (both P < 0.05). There was no significant difference in the incidence of adverse reactions between group A and group C ( P > 0.05). Conclusion:Atorvastatin and high-dose simvastatin alone combined with trimetazidine can achieve good therapeutic effects on chronic heart failure. Both combined therapies are beneficial to improve heart function and reduce myocardial damage. However, atorvastatin combined with trimetazidine is safer than high-dose simvastatin combined with trimetazidine.

A review of effects of atorvastatin in cancer therapy.

Cancer is one of the most challenging diseases to manage. A sizeable number of researches are done each year to find better diagnostic and therapeutic strategies. At the present time, a package of chemotherapy, targeted therapy, radiotherapy, and immunotherapy is available to cope with cancer cells. Regarding chemo-radiation therapy, low effectiveness and normal tissue toxicity are like barriers against optimal response. To remedy the situation, some agents have been proposed as adjuvants to improve tumor responses. Statins, the known substances for reducing lipid, have shown a considerable capability for cancer treatment. Among them, atorvastatin as a reductase (HMG-CoA) inhibitor might affect proliferation, migration, and survival of cancer cells. Since finding an appropriate adjutant is of great importance, numerous studies have been conducted to precisely unveil antitumor effects of atorvastatin and its associated pathways. In this review, we aim to comprehensively review the most highlighted studies which focus on the use of atorvastatin in cancer therapy.

Atorvastatin Efficacy in the Management of Mild to Moderate Hospitalized COVID-19: A Pilot Randomized Triple-blind Placebo- controlled Clinical Trial.

BACKGROUND: Statins are first-line lipid-lowering agents with tolerable adverse reactions, low cost, and high availability worldwide. The potent anti-inflammatory, antioxidant, anti-thrombotic and immunomodulatory effects of statins propose them as an option against COVID-19 infection. OBJECTIVE: In this randomized triple-blind placebo-controlled clinical trial, we have investigated the atorvastatin efficacy in the management of mild to moderate hospitalized COVID-19 patients. METHODS: In this study, 52 mild to moderate hospitalized COVID-19 patients who fulfilled the inclusion criteria were allocated to the treatment group to receive 40 mg atorvastatin orally once daily for two weeks (n=26) or the placebo group (n=26). Patients' symptoms and laboratory investigations were assessed at baseline and during the follow-up period. We also evaluated the duration of hospitalization and supplemental oxygen therapy as endpoints. RESULTS: After 14-day of follow-up, the oxygen saturation (SaO2) was significantly higher, and the serum high sensitivity C-reactive protein (hs-CRP) level was lower in the treatment group compared to the placebo group. Moreover, at the end of the followup in the treatment group, the lymphocyte count was higher, and the duration of symptom resolution was shorter but not significant. Additionally, in the treatment group, the length of supplemental oxygen therapy and hospitalization duration were meaningfully shorter. Our results revealed that the mortality rate was almost twice higher in the placebo group compared to the treatment group, without any significant adverse drug reaction. CONCLUSION: Atorvastatin significantly reduces supplemental oxygen need, hospitalization duration, and serum hs-CRP level in mild to moderate hospitalized COVID-19 patients.

Antidiabetics, Anthelmintics, Statins, and Beta-Blockers as Co-Adjuvant Drugs in Cancer Therapy.

Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients' daily treatment for nonmalignant-associated pathology and have known, light toxicity profiles. It is quite common for a given patient's daily administration schedule to include two or three of these drugs for the duration of their treatment. We chose to review the latest literature concerning metformin, employed as a first-line treatment for type 2 diabetes; mebendazole, as an anthelmintic; atorvastatin, as a cholesterol-lowering drug; propranolol, used in cardiovascular diseases as a nonspecific inhibitor of beta-1 and beta-2 adrenergic receptors. At the same time, certain key action mechanisms make them feasible antitumor agents such as for mitochondrial ETC inhibition, activation of the enzyme adenosine monophosphate-activated protein kinase, amelioration of endogenous hyperinsulinemia, inhibition of selective tyrosine kinases (i.e., VEGFR2, TNIK, and BRAF), and mevalonate pathway inhibition. Despite the abundance of results from in vitro and in vivo studies, the only solid data from randomized clinical trials confirm metformin-related oncological benefits for only a small subset of nondiabetic patients with HER2-positive breast cancer and early-stage colorectal cancer. At the same time, clinical studies confirm metformin-related detrimental/lack of an effect for lung, breast, prostate cancer, and glioblastoma. For atorvastatin we see a clinical oncological benefit in patients and head and neck cancer, with a trend towards radioprotection of critical structures, thus supporting the role of atorvastatin as a promising agent for concomitant association with radiotherapy. Propranolol-related increased outcomes were seen in clinical studies in patients with melanoma, breast cancer, and sarcoma.

Possible mechanism and Atorvastatin-based treatment in cupping therapy-related subdural hematoma: A case report and literature review.

Subdural hematoma (SDH) is one of the most lethal types of traumatic brain injury. SDH caused by Intracranial Pressure Reduction (ICPR) is rare, and the mechanism remains unclear. Here, we report three cases of SDH that occurred after substandard cupping therapy and are conjected to be associated with ICPR. All of them had undergone cupping treatments. On the last cupping procedure, they experienced a severe headache after the cup placed on the occipital-neck junction (ONJ) was suddenly removed and were diagnosed with SDH the next day. In standard cupping therapy, the cups are not usually placed on the ONJ. We speculate that removing these cups on the soft tissue over the cisterna magna repeatedly created localized negative pressure, caused temporary but repeated ICPR, and eventually led to SDH development. The Monro-Kellie Doctrine can explain the mechanism behind this - it states that the intracranial pressure is regulated by a fixed system, with any change in one component causing a compensatory change in the other. The repeated ICPR promoted brain displacement, tearing of the bridging veins, and development of SDH. The literature was reviewed to illustrate the common etiologies and therapies of secondary ICPR-associated SDH. Despite the popularity of cupping therapy, its side effects are rarely mentioned. This case is reported to remind professional technicians to fully assess a patient's condition before cupping therapy and ensure that the cups are not placed at the ONJ.

Hypolipidemic Activity of Olive Oil-Based Nanostructured Lipid Carrier Containing Atorvastatin.

Currently, hyperlipidemia is a growing health issue that is considered a risk factor for obesity. Controlling body weight and modifying life style in most of cases are not adequate and the condition requires medical treatment. Statin drugs (mainly Atorvastatin (ATO)), have been used broadly and for long time as medications for handling higher levels of lipid, especially bad cholesterol, which accordingly controls the prevalence of obesity. Still, the obstacle that stands in front of any formulation is the poor solubility of the drug. Low solubility of ATO came up with poor absorption as well as poor bioavailability. This paved the way for the present study, which aimed to exploit nanotechnology and develop certain nanolipid carriers that could accommodate hydrophobic drugs, such as ATO. Nanostructured lipid carrier (NLC) containing ATO was fabricated using olive oil. Olive oil is natural plant oil possessing confirmed hypolipidemic activity that would help in improving the efficacy of the formulation. Via applying the Quality by Design (QbD) approach, one NLC formula was selected to be optimized based on appropriate size and higher entrapment. Optimized ATO-NLC was scrutinized for zeta potential, in vitro study and kinetic profile. Moreover, stability testing and in vivo hypolipidemic behavior was conducted. The optimized NLC formulation seemed to show particle size (254.23 nm) with neutral zeta potential (-1.77 mV) and entrapment efficiency (69.56%). The formulation could be prolonged for 12 h and provided higher % of release (97.17%). Stability testing confirmed the role of modifying the surface of the formulation with PEG-DSPE in providing a highly stable formulation that could withstand three months storage in two altered conditions. Ultimately, optimized ATO-NLC could successfully lower total cholesterol level in rats induced with obesity and fed a high-fat diet. Remarkably, ATO-NLC prepared with olive oil, in addition to shielding its surface, would provide a stable formulation that holds up the synergistic action between olive oil and ATO.