Comparison of Efficacy of Atorvastatin and Rosuvastatin in Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis.

Acute coronary syndrome (ACS) remains a leading cause of morbidity and mortality worldwide. Statins, particularly atorvastatin, and rosuvastatin, are crucial in managing cholesterol levels and reducing cardiovascular risk in ACS patients. However, direct comparative studies between these two statins are limited. This meta-analysis aimed to compare the efficacy of atorvastatin and rosuvastatin in reducing major adverse cardiovascular events (MACE) and all-cause mortality in patients with ACS. A comprehensive literature search was conducted in PubMed, Embase, Cochrane Library, and Scopus for studies published up to July 2024. Randomized controlled trials and observational studies directly comparing atorvastatin and rosuvastatin in ACS patients were included. The primary outcomes were the incidence of MACE and all-cause mortality. Six studies involving 4195 patients were included in the meta-analysis. Pooled analysis showed no statistically significant difference between atorvastatin and rosuvastatin in reducing MACE [risk ratio (RR): 0.91, 95% confidence interval (CI): 0.68 to 1.22, p-value: 0.54] or all-cause mortality (RR: 0.94, 95% CI: 0.52 to 1.70, p-value: 0.83). No significant heterogeneity was observed among the studies (I-square: 0% for both outcomes). This meta-analysis suggests that atorvastatin and rosuvastatin have comparable efficacy in reducing MACE and all-cause mortality in ACS patients. These findings provide clinicians with flexibility in choosing between these statins based on individual patient factors. However, further large-scale randomized controlled trials are needed to confirm these results and explore potential differences in specific patient subgroups.

The implications of atorvastatin administration and the potential protective role of omega-3 on the submandibular salivary gland of albino rats (Histological, Histochemical, Ultrastructure, and Biochemical Study).

BACKGROUND: Hyperlipidemia is a risky condition that can lead to atherosclerosis and other cardiovascular problems. Statins are used to treat hyperlipidemia. The most recommended medicine to treat hyperlipidemia is atorvastatin. On the contrary, clinical trials validated statins' negative effects. Omega-3 fatty acids have antioxidant properties and have been shown to improve a variety of disease processes in the general population, including inflammatory and immunological pathways, various cardiovascular diseases, and lipid regulation. The present research aimed to determine how atorvastatin affected the submandibular salivary gland (SMG) and whether omega-3 may have a protective impact. METHODS: Thirty adult male albino rats were divided into three equal groups and received drugs orally as a single daily dose for one week. Control group (I): received normal saline. Atorvastatin group (II): received a dose of 80 mg Kg-1 of Atorvastatin. Group III: received Omega-3 before Atorvastatin. All rats were sacrificed 2 h following the last dose, and blood samples were gathered for the biochemical study of fasting blood glucose level (FBGL). Specimens were obtained and processed for histological and histochemical studies. RESULTS: Atorvastatin-treated rats showed degeneration of SMG acini. The acinar cells showed cytoplasmic vacuoles with dilated RER. Histochemical results revealed a marked decrease in total proteins. The biochemical study revealed an elevation in FBGL. The administration of Omega-3 with Atorvastatin minimizes these changes. CONCLUSION: Atorvastatin has been proven to induce histological changes in SMG, and these changes can be attenuated by Omega-3. However, Omega-3 has no effect on FBGL.

Atorvastatin-Loaded Dissolving Microarray Patches for Long-Acting Microdepot Delivery: Comparison of Nanoparticle and Microparticle Drug Formulations.

The increasing popularity of prolonged-release dosage forms, owing to their ability to provide continuous drug release after administration, has significantly improved patient compliance and overall quality of life. However, achieving prolonged release beyond 24 h frequently requires the use of invasive methods, including injections or implants, which may prove challenging for people suffering from needle phobia. This study introduces atorvastatin (ATR) microparticles (MPs) or nanocrystal (NCs) dissolving microarray patches (D-MAPs) as a noninvasive alternative for intradermal drug delivery over a two-week period for the management of hyperlipidemia. The MP-loaded D-MAPs exhibited an average drug loading of 5.15 ± 0.4 mg of ATR per patch, surpassing the 2.4 ± 0.11 mg/patch observed with NC-loaded D-MAPs. Skin deposition studies demonstrated the superior performance of MP D-MAPs, which delivered 2.0 ± 0.33 mg of ATR per 0.75 cm2 patch within 24 h, representing 38.76% of the initial amount of drug loaded. In contrast, NC D-MAPs delivered approximately 0.89 ± 0.12 mg of ATR per 0.75 cm2 patch at 24 h, equivalent to 38.42 ± 5.13% of the initial ATR loaded. Due to their favorable results, MP D-MAPs were chosen for an in vivo study using Sprague-Dawley rats. The findings demonstrated the capacity of D-MAPs to deliver and attain therapeutically relevant ATR concentrations (>20 ng/mL) for 14 days after a single 24-h application. This study is the first to successfully demonstrate the long-acting transdermal delivery of ATR using MP-loaded D-MAPs after a 24-h single-dose application. The innovative D-MAP system, particularly when loaded with MP, arises as a promising, minimally invasive, long-acting substitute for ATR delivery. This technology has the potential to improve patient compliance and therapeutic outcomes while also significantly advancing the field of transdermal drug delivery.

Self-nanoemulsifying drug delivery system for nebulization: fabrication and evaluation for systemic delivery of atorvastatin.

The study undertakes the development of an atorvastatin-loaded self-nanoemulsifying drug delivery system (SNEDDS) to improve its bioavailability. The SNEDDS were fabricated using oleic acid, Tween 80, and Span 80 by spontaneous emulsification. The SNEDDS were assessed for their particle size distribution, zeta potential, morphology, drug content, surface tension, viscosity, and drug release. The aerodynamic performance of the SNEDDS was evaluated using an Andersen cascade impactor, while the lipid-lowering potential of the SNEDDS was determined in Wistar rats using the analyzer "Microlab 300." The particle size of the SNEDDS ranged from 36 to 311 nm, with a polydispersity index (PDI) of 0.25-0.40. The zeta potential of the SNEDDS fluctuated from - 29.22 to - 38.26 mV, which declined to - 4.55 mV in the case of F5. The chitosan-coated formulation (F5) exhibited a higher viscosity (22.12 mPa s) and lower surface tension (0.056 dyne/cm) than other formulations (F1-F4). The non-coated formulation exhibited a significantly higher burst drug release, followed by a sustained drug release pattern (p ≤ 0.05) as compared to the coated formulation (F5). The nebulized SNEDDS achieved a dispersed fraction of 87 to 97%, where notably higher aerosol dispersion from F4 was attributed to its smaller particle size and circularity. The inhaled fraction of nebulized SNEDDS was 74-87%. The size of the SNEDDS droplets was the primary determinant affecting the aerodynamic performance of the SNEDDS during nebulization. The chitosan-coated SNEDDS achieved a higher antihyperlipidemic effect than marketed tablets, which shows the suitability of F5 for effective systemic delivery of atorvastatin through the lung.

Comparative Study Between the Effects of High Doses of Rosuvastatin and Atorvastatin on Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Most studies reported that treating ST-Elevation Myocardial Infarction (STEMI) patients with high doses of rosuvastatin or atorvastatin could improve left ventricular remodeling and cardiac function. PURPOSE: The current study compared the impact of high doses of rosuvastatin and atorvastatin on hypertrophy, fibrosis markers, serum inflammatory markers, and left ventricular function in STEMI patients after primary percutaneous coronary intervention (PCI). METHOD: After primary PCI, eighty STEMI patients were randomized to receive either 20 mg of rosuvastatin (n = 40) or 40 mg of atorvastatin (n = 40) once daily for 3 months. Soluble Suppression of Tumorigenicity-2 (sST2), Matrix Metalloproteinase-9 (MMP9), C-Reactive Protein (CRP), lipid parameters, liver enzymes, and echocardiographic parameters were assessed for the two groups at baseline and after 3 months. RESULTS: After 3 months of treatment, a statistically significant reduction was observed in the rosuvastatin group regarding the levels of CRP (16 ± 6 vs. 20 ± 10 mg/L, P = 0.024) and MMP9 (104 ± 33 vs. 130 ± 42 ng/L, P = 0.003) compared with the atorvastatin group. The median percentage decrease in sST2 level in the rosuvastatin group was higher (6.1%) than in the atorvastatin group (2.3%) after 3 months of treatment. Also, in the rosuvastatin group, LVEF was significantly increased (48.5 ± 9 vs. 43.5 ± 11%, P = 0.029), while LVEDV and LVESV were significantly decreased compared to those of the atorvastatin group (101 [81/135] vs. 134 [100/150] ml, P = 0.041) (53 [37/75] vs. 73 [52/92] ml, P = 0.033), respectively. CONCLUSION: High-intensity rosuvastatin was superior to high-intensity atorvastatin in reducing the inflammatory response and myocardial fibrosis, thus improving ventricular remodeling and cardiac function better in STEMI patients. TRIAL REGISTRATION: This randomized controlled trial was registered on October 11, 2022, on ClinicalTrials.gov under registration number: NCT05895123 "retrospectively registered".

The CNIC polypill (Acetylsalicylic acid + Atorvastatin + Rampril) in secondary prevention of cardiovascular disease in patients with type 2 diabetes: A comparative analysis with alternative therapeutic approaches.

BACKGROUND: Patients with type 2 DM (T2DM) and established cardiovascular disease (CVD) are at high risk of recurrent CV events. We analysed the use of the CNIC-polypill (acetylsalicylic acid, ramipril, and atorvastatin) compared with other therapeutic strategies in patients with T2DM and CVD from the retrospective NEPTUNO study. METHODS: Patients were stratified into four therapeutic approaches: CNIC-polypill, its monocomponents as loose medications, equipotent medications, and other therapies. Outcomes included the 2-year cumulative incidence and risk of recurrent major adverse CV events (MACE) and CV death, risk factors control, medication persistence, and utilisation of healthcare resources and costs. RESULTS: After two years, T2DM patients treated with Monocomponents, Equipotent drugs, or Other therapies had increased recurrent MACE risk compared to CNIC-polypill (11 %, 23 %, and 44 %, respectively; P < 0.05) and shorter median time to CV events (305-377 vs. 396 days; P < 0.05). The CNIC-polypill group achieved a significant 11.2 % increase in patients reaching LDL-c targets <70 mg/dL, outperforming other strategies. It also exhibited superior triglyceride control and a higher proportion achieving the <130/80 mmHg blood pressure goal. The CNIC-polypill cohort displayed significantly higher 24-month persistence (71.5 % vs. 54.7 %-58.3 %, p < 0.05) and lower mean adjusted costs per patient (€5083 vs. €6000-€6523; p < 0.05). In a comparative analysis, T2DM patients had lower baseline LDL-c and total cholesterol levels than non-T2DM counterparts yet experienced a higher incidence of recurrent MACE over two years. CONCLUSION: The CNIC-polypill (ASA, atorvastatin and ramipril) emerged as a promising treatment for patients with CVD, particularly those with T2DM, offering improved clinical outcomes and economic efficiency.

Revitalizing common drugs for antibacterial, quorum quenching, and antivirulence potential against Pseudomonas aeruginosa: in vitro and in silico insights.

In the post-antibiotic era, antivirulence therapies are becoming refractory to the clinical application of existing antimicrobial regimens. Moreover, in an attempt to explore alternate intervention strategies, drug repurposing is gaining attention over development of novel drugs/antimicrobials. With the prevalence of multidrug resistance and high medical burden associated with Pseudomonas aeruginosa, there is an urgent need to devise novel therapeutics to combat this bacterial pathogen. In this context, the present study was undertaken to scrutinize the anti-quorum sensing (QS) and antivirulence potential of commonly consumed drugs such as fexofenadine (FeX), ivermectin (IvM), nitrofurantoin (NiT), levocetrizine (LvC), atorvastatin (AtS), and aceclofenac (AcF), against P. aeruginosa. The methodology involved assessment of antibacterial activity against P. aeruginosa PAO1 and quorum quenching (QQ) potential using Agrobacterium tumefaciens NTL4 biosensor strain. The antivirulence prospects were investigated by estimating the production of hallmark virulence factors in P. aeruginosa accompanied by molecular docking to predict drug associations with the QS receptors. Interestingly, all the drugs harbored antibacterial, anti-QS, and antivirulence potential in vitro, which consequently disrupted QS circuits and attenuated pseudomonal virulence phenotypically by significantly lowering the production of pyocyanin, hemolysin, pyochelin, and total bacterial protease in vitro. Moreover, the findings were validated by computational studies that predicted strong molecular interactions between the test drugs and QS receptors of P. aeruginosa. Hence, this study is the first to suggest the prospect of repurposing FeX, IvM, NiT, LvC, AtS, and AcF against P. aeruginosa.

Evaluation of changes in the global longitudinal strain for left ventricular function before and after eight weeks of taking high dose of atorvastatin in patients with coronary slow flow phenomenon.

BACKGROUND: Coronary Slow Flow Phenomenon (CSFP) is a well-recognized clinical entity characterized by delayed opacification of coronary arteries in the presence of a normal coronary angiogram. The objective of this study was determined and compared left ventricle (LV)strain in patients with CSFP before and after receiving a high-dose atorvastatin. MATERIALS AND METHODS: This cross-sectional study was conducted on 51 patients with CSFP from the beginning of 2021 to the end of September 2022. Trans-thoracic Echocardiogram (TTE) was performed by an echocardiography specialist. Thereafter, the patient's basic information was entered into the researcher's checklist after treatment with atorvastatin 40 mg daily for eight consecutive weeks. After eight weeks, the patients were subjected again to TTE. The data were analyzed in SPSS statistical software. RESULTS: The mean LV-GLS before taking atorvastatin was - 16.53%±3.63%. The mean LV-GLS after taking atorvastatin was 17.57%±3.53% (P.value = 0.01). The mean LV function before taking atorvastatin was 48.82%±9.19%. Meanwhile, the mean LV function after taking atorvastatin was 50.59%±7.91% (P = 0.01). There was no significantly change in left atrium volume (49.88 ± 0.68 vs. 49.9 + 0.67) after 8 weeks taking atorvastatin (P = 0.884). CONCLUSION: The plasma ET-1 levels are elevated in CSFP patients, and atorvastatin improves coronary flow and endothelial function. As evidenced by the results of this study, the daily intake of 40 mg of oral atorvastatin during eight consecutive weeks in patients with CSFP significantly improved LV strain and LV function, however atorvastatin does not have a significant effect on improving the right ventricular function and pulmonary artery systolic pressure.

Comparative effect of atorvastatin and risperidone on modulation of TLR4/NF-κB/NOX-2 in a rat model of valproic acid-induced autism.

BACKGROUND: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism. METHODS: On gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed. RESULTS: Male offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group. CONCLUSIONS: The research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD.

Phase 1 Evaluation of the Bioequivalence and Drug-Drug Interaction Potential of a Novel Fixed-Dose Combination of Ezetimibe, Atorvastatin, and Amlodipine.

A fixed-dose combination (FDC) of ezetimibe, atorvastatin, and amlodipine has been developed to improve medication adherence among patients with cardiovascular diseases. In a randomized, open-label, multiple-dose, fixed-sequence study involving 34 participants (Study 1), the potential drug-drug interaction between ezetimibe/atorvastatin FDC and amlodipine was evaluated. Additionally, a randomized, open-label, crossover study with 60 participants (Study 2) compared the pharmacokinetics (PKs) of ezetimibe/atorvastatin/amlodipine FDC to those of individual formulations. Co-administration of the ezetimibe/atorvastatin FDC and amlodipine did not significantly alter the PKs of either drug. However, amlodipine resulted in a slight increase in systemic exposure to atorvastatin by approximately 23%. Geometric mean ratios (FDC to individual formulations) and 90% confidence intervals of area under the time-concentration curve at steady state during dosing interval (AUCτ, ss) and maximum concentration at steady state (Cmax, ss) or amlodipine, atorvastatin, and ezetimibe were all within the bioequivalent range (0.8-1.25), confirming bioequivalence. Moreover, the FDC of ezetimibe, atorvastatin, and amlodipine exhibited comparable tolerability to corresponding individual formulations.

Corrigendum: Effect of a high dose atorvastatin as added-on therapy on symptoms and serum AMPK/NLRP3 inflammasome and IL-6/STAT3 axes in patients with major depressive disorder: randomized controlled clinical study.

[This corrects the article DOI: 10.3389/fphar.2024.1381523.].

A comparison of the antiepileptogenic efficacy of two rationally chosen multitargeted drug combinations in a rat model of posttraumatic epilepsy.

Post-traumatic epilepsy (PTE) is a recurrent and often drug-refractory seizure disorder caused by traumatic brain injury (TBI). No single drug treatment prevents PTE, but preventive drug combinations that may prophylax against PTE have not been studied. Based on a systematic evaluation of rationally chosen drug combinations in the intrahippocampal kainate (IHK) mouse model of acquired epilepsy, we identified two multi-targeted drug cocktails that exert strong antiepileptogenic effects. The first, a combination of levetiracetam (LEV) and topiramate, only partially prevented spontaneous recurrent seizures in the model. We therefore added atorvastatin (ATV) to the therapeutic cocktail (TC) to increase efficacy, forming "TC-001". The second cocktail - a combination of LEV, ATV, and ceftriaxone, termed "TC-002" - completely prevented epilepsy in the mouse IHK model. In the present proof-of-concept study, we tested whether the two drug cocktails prevent epilepsy in a rat PTE model in which recurrent electrographic seizures develop after severe rostral parasagittal fluid percussion injury (FPI). Following FPI, rats were either treated over 3-4 weeks with vehicle or drug cocktails, starting either 1 or 4-6 h after the injury. Using mouse doses of TC-001 and TC-002, no significant antiepileptogenic effect was obtained in the rat PTE model. However, when using allometric scaling of drug doses to consider the differences in body surface area between mice and rats, PTE was prevented by TC-002. Furthermore, the latter drug cocktail partially prevented the loss of perilesional cortical parvalbumin-positive GABAergic interneurons. Plasma and brain drug analysis showed that these effects of TC-002 occurred at clinically relevant levels of the individual TC-002 drug components. In silico analysis of drug-drug brain protein interactions by the STITCH database indicated that TC-002 impacts a larger functional network of epilepsy-relevant brain proteins than each drug alone, providing a potential network pharmacology explanation for the observed antiepileptogenic and neuroprotective effects observed with this combination.

HMGCR Inhibitor Restores Mitochondrial Dynamics by Regulating Signaling Cascades in a Rodent Alzheimer's Disease Model.

Atorvastatin an HMGCR inhibitor may play a role in enhancing spatial and long-term memory and combating anxious behavior deficits induced by Aß1-42. Behavioral deficit studies, immunoblotting for the antioxidant/apoptotic protein expression, flow cytometry (FACS) for mitochondrial ROS, membrane potential (▲ψm), and histopathological alterations were performed against Aß1-42 toxicity. Aß1-42 was infused directly into the brain through i.c.v for the establishment of the AD model. Atorvastatin (ATOR) was administered orally and was used to treat AD in adult male Wistar rats aged between 200 and 250 g. We confirmed that ATOR administration significantly attenuates the Aß1-42-induced cognitive decline targeted mitochondrial-mediated age-dependent disease progression. Nrf2 stabilizes to interact SOD2 antioxidant enzyme, allowing transcriptional activity by the steep increase in ▲ψm and a reduction in ROS by activating mitochondrial superoxide scavenger and Nrf2-dependent pathway. These findings confirmed that ATOR has the potential efficacy to modulate the interference in cognitive decline induced by Aß1-42.

Minimal Transfer of Atorvastatin and Its Metabolites in Human Milk: A Case Series.

Background: Statins are historically contraindicated during breastfeeding due to theoretical concerns of disruptions in infant development from drug exposure and nutritional changes in milk. Breastfeeding mothers requiring statins often discontinue statins or postpone treatment until breastfeeding cessation, contributing to delays in treatment up to 14 years. This study aims to determine the transfer of atorvastatin and its active metabolites into human milk and evaluate the infant's risk of drug exposure. Materials and Methods: Milk samples and health information were released from the InfantRisk Human Milk Biorepository for three women taking 20 mg, 40 mg, and 80 mg of atorvastatin daily at steady state conditions. The concentration of atorvastatin (AT) and its active metabolites, ortho-hydroxy AT (2OH AT) and para-hydroxy AT (4OH AT), was quantified in timed milk samples using liquid chromatography-mass spectrometry. Results: The highest absolute infant dose of AT was 0.00027 mg/kg/day, and the highest weight-adjusted relative infant dose of the combined analytes was 0.09%, far below established thresholds for infant safety. Milk cholesterol levels were within previously established norms in the range of 10 mg/dL. The mothers reported no adverse outcomes in the two exposed infants. Conclusions: The transfer of atorvastatin and its metabolites was exceedingly low. While the impact on milk composition in states of hyperlipidemia (whether treated or untreated) is not well understood, it is unlikely that the drug in the milk would be present in clinically significant levels to adversely affect a breastfed infant.

Investigating the Effects of Simultaneous Administration of Melatonin and Atorvastatin against High Glucose-Induced Oxidative Stress and Apoptosis in Cultured Chondrocytes.

OBJECTIVE: Osteoarthritis (OA) is a prevalent joint disorder categorized into phenotypic subtypes, including those associated with age, traumatic events, and metabolic syndrome. In the aging population, type 2 diabetes mellitus (T2DM) and osteoarthritis (OA) frequently coexist. This can result in higher rates of disability and a greater financial burden. This study aimed to investigate the protective effects of melatonin and atorvastatin together against oxidative stress and apoptosis induced by high glucose in C28I2 human chondrocytes. MATERIAL AND METHODS: After being pretreated for 6 hours with melatonin (10 and 100 µM) and atorvastatin (0.01 and 0.1 µM), C28I2 cells were exposed to a high concentration of D-glucose (75 mM) for 72 hours. The impact of a high D-glucose concentration (75 mM), with or without melatonin and/or atorvastatin, on cell viability, intra-cellular ROS generation, lipid peroxidation level, antioxidant activities, and the expression of proteins, including Bax, Bcl-2, and caspase-3, was analyzed. RESULTS: Melatonin and atorvastatin combination effectively inhibited high glucose-induced cytotoxicity, ROS production, and MDA and mitochondrial membrane potential levels. The combination of melatonin and atorvastatin was more successful in reducing ROS production compared to each of the drugs alone. Melatonin, but not atorvastatin, reversed high glucose-induced alteration in the catalase activity. Furthermore, the combination of melatonin and atorvastatin significantly enhanced the ability of each medication to lower the expression of pro-apoptotic protein Bax. CONCLUSION: The combination of melatonin and atorvastatin exerted greater protective effects against hyperglycemia-induced toxicity in chondrocytes.

Anti-Inflammatory Effect of Atorvastatin on Primary Human Endothelial Cells Incubated under Genotoxic Load.

The level of cytokine expression was measured in human coronary artery (HCAEC) and internal thoracic artery (HITAEC) endothelial cells exposed to 500 ng/ml alkylating mutagen mitomycin C (MMC) and 5 µM atorvastatin. It was found that treatment of MMC-exposed HCAEC with atorvastatin decreased secretion of macrophage migration inhibitory factor (MIF), IL-8, and IL8 gene expression, but increased the expression of SERPINE1 gene encoding the PAI-1 protein. In atorvastatin-treated HITAEC, the concentration of MIF protein and the expression of the IL8 and SERPINE1 genes were reduced. We can conclude that atorvastatin prevents proinflammatory activation of endothelial cells cultured under conditions of genotoxic load. However, the molecular mechanisms of this effect require further research.

Effect of Atorvastatin combined with Irbesartan in the treatment of early diabetic nephropathy.

Objective: To explore the effect of Atorvastatin combined with Irbesartan in the treatment of early diabetic nephropathy (DN). Methods: Clinical data from 153 patients with early DN, admitted to Huzhou Central Hospital from January 2020 to December 2022, was retrospectively selected. Patients were divided into two groups based on the treatment they received: patients received Irbesartan treatment alone were assigned to Irbesartan group (n=74); patients received Irbesartan combined with Atorvastatin were assigned to combined group (n=79). Levels of renal function indicators, renal fibrosis indicators, micro inflammatory status indicators, and incidence of adverse reactions were compared between the two groups before and after the treatment. Results: After the treatment, indicators of renal function, renal fibrosis and micro-inflammation in both groups significantly decreased compared to pretreatment levels (P<0.05), and were significantly lower in the combined group compared to Irbesartan group (P<0.05). There was no significant difference in the incidence of adverse reactions between the groups (P>0.05). Conclusions: Compared with Irbesartan alone, Atorvastatin combined with Irbesartan is more effective in the treatment of early DN. Combined treatment regimen is able to effectively reduces the micro-inflammatory state, improve renal function and fibrosis, and is not associated with the increased risk of adverse reactions.

Evaluating the Protective Effect of Melatonin on Atorvastatin-induced Mitochondrial Toxicity in Pancreatic Beta Cells.

BACKGROUND: Atorvastatin and other statins belong to a category of cholesterollowering drugs, which may cause some damage to pancreatic cells despite their effectiveness. AIMS: The present study investigated the effects of melatonin against atorvastatin-induced toxicity on islets of Langerhans and CRI-D2 cells. METHODS: The MTT assay was used to determine cell viability. The effect of various concentrations of melatonin (0,10, 50, 100, 250, 500 and 1000 µM) on CRI-D2 cell viability was evaluated for 24 hours to determine the non-cytotoxic concentrations of melatonin. Additionally, cells were treated with different concentrations of atorvastatin (10, 100, and 150 ng/mL) for 24 hours to determine a concentration that could induce the maximum cell death. After selecting the appropriate concentrations for melatonin, cells were treated with atorvastatin (10, 100, and 150 ng/ml) and melatonin (10 and 100 µM) simultaneously for a period of 24 hours. Malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase, catalase, and glutathione peroxidase activity were assessed as indicators of oxidative stress. To assess mitochondrial function, the ratio of adenosine diphosphate (ADP) to adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) were measured. RESULTS: Atorvastatin markedly raised ROS and MDA levels. This result was associated with a decrease in MMP, an increase in the ADP/ATP ratio, and a change in the activity of antioxidant enzymes. Atorvastatin (150 ng/mL)-induced mitochondrial damage was alleviated by concurrent melatonin and atorvastatin therapy. CONCLUSION: These results suggest that melatonin has a protective effect against atorvastatininduced toxicity in the mitochondria of pancreatic cells.

Effects of in utero benzo[a]pyrene exposure on the testis of rats during puberty and the protective effect of atorvastatin.

Benzo[a]pyrene (BaP) is a contaminant that is generated in the environment through processes such as smoke, incomplete combustion of fossil fuels, vehicle exhaust emissions, entry into the body is through inhalation, and consumption of contaminated food. It is an omnipresent environmental pollutant with unavoidable exposure. BaP metabolites are observed in the male reproductive system, especially in the testes and epididymis of animals, and are responsible for reduced testicular and epididymal function. The protective effect of atorvastatin (ATV) on testicular damage was investigated previously. The aim of the present study was to investigate the protective effect of ATV on testicular toxicity induced by benzo[a]pyrene (BaP) during pregnancy in Wistar rats. This experimental laboratory study involved 40 adult rats, divided into seven groups and maintained under standard environmental conditions. The groups received different diets [control, corn oil, ATV (10 mg/kg), BaP (10 and 20 mg/kg), and ATV + BaP (10 and 20 mg/kg)] at gestation Days 7-16, orally. Male offspring were examined 10 weeks after birth. Testis and serum samples were collected, and testosterone level, malondialdehyde (MDA), and glutathione (GSH) were measured. Histological and immunohistochemical assays were performed under a light microscope. Statistical analysis was conducted using SPSS, with analysis of variance and Tukey tests to assess significant differences between groups. ATV significantly reduced MDA, a marker of lipid peroxidation and oxidative stress in rat testes following BaP administration. Treatment with ATV at doses of 10 mg/kg increased GSH levels, correcting disruptions in the antioxidant system caused by BaP. Testosterone concentration in rats treated with ATV and BaP substantially prevented the decrease induced by BaP. Histomorphometry revealed that ATV significantly prevented the detrimental effects of BaP on the thickness of spermatogenic epithelium and the diameter of seminiferous tubules. Under ATV treatment, testicular tissue histopathology improved, and spermatogenesis returned to a almost back to normal state. Caspase-3 expression decreased, and apoptosis activity in testicular tissue improved under ATV treatment, indicating a positive effect of ATV in reducing apoptotic damage caused by BaP. In conclusion, exposure to BaP can induce oxidative stress-related damage to testicular tissue, as evidenced by an increase in MDA levels, which ATV treatment can mitigate. Additionally, ATV enhances intracellular antioxidant GSH and protects the testes against BaP-induced damage while increasing testosterone levels, which are reduced due to exposure to BaP.