Hypolipidemic Research Articles

Comprehensive Analysis of Drug Utilization Patterns, Gender Disparities, Lifestyle Influences, and Genetic Factors: Insights from Elderly Cohort Using g-Nomic® Software.

Polypharmacy is a global healthcare concern, especially among the elderly, leading to drug interactions and adverse reactions, which are significant causes of death in developed nations. However, the integration of pharmacogenetics can help mitigate these risks. In this study, the data from 483 patients, primarily elderly and polymedicated, were analyzed using Eugenomic®'s personalized prescription software, g-Nomic®. The most prescribed drug classes included antihypertensives, platelet aggregation inhibitors, cholesterol-lowering drugs, and gastroprotective medications. Drug-lifestyle interactions primarily involved inhibitions but also included inductions. Interactions were analyzed considering gender. Significant genetic variants identified in the study encompassed ABCB1, SLCO1B1, CYP2C19, CYP2C9, CYP2D6, CYP3A4, ABCG2, NAT2, SLC22A1, and G6PD. To prevent adverse reactions and enhance medication effectiveness, it is strongly recommended to consider pharmacogenetics testing. This approach shows great promise in optimizing medication regimens and ultimately improving patient outcomes.

Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.

Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.

Catalytic Synthesis of (S)-CHBE by Directional Coupling and Immobilization of Carbonyl Reductase and Glucose Dehydrogenase.

Ethyl (S)-4-chloro-3-hydroxybutyrate ((S)-CHBE) is an important chiral intermediate in the synthesis of the cholesterol-lowering drug atorvastatin. Studying the use of SpyTag/SpyCatcher and SnoopTag/SnoopCatcher systems for the asymmetric reduction reaction and directed coupling coenzyme regeneration is practical for efficiently synthesizing (S)-CHBE. In this study, Spy and Snoop systems were used to construct a double-enzyme directed fixation system of carbonyl reductase (BsCR) and glucose dehydrogenase (BsGDH) for converting 4-chloroacetoacetate (COBE) to (S)-CHBE and achieving coenzyme regeneration. We discussed the enzymatic properties of the immobilized enzyme and the optimal catalytic conditions and reusability of the double-enzyme immobilization system. Compared to the free enzyme, the immobilized enzyme showed an improved optimal pH and temperature, maintaining higher relative activity across a wider range. The double-enzyme immobilization system was applied to catalyze the asymmetric reduction reaction of COBE, and the yield of (S)-CHBE reached 60.1% at 30 °C and pH 8.0. In addition, the double-enzyme immobilization system possessed better operational stability than the free enzyme, and maintained about 50% of the initial yield after six cycles. In summary, we show a simple and effective strategy for self-assembling SpyCatcher/SnoopCatcher and SpyTag/SnoopTag fusion proteins, which inspires building more cascade systems at the interface. It provides a new method for facilitating the rapid construction of in vitro immobilized multi-enzyme complexes from crude cell lysate.

Remnant cholesterol, LDL cholesterol, and apoB absolute mass changes explain results of the PROMINENT trial

Background and aimsThe PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides and remnant cholesterol. We tested the hypothesis that absolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B explain the results of the PROMINENT trial. MethodsAmong 108,431 individuals from the Copenhagen General Population Study (CGPS), those who met the key inclusion criteria of the PROMINENT trial were analyzed to mimic the trial design. Endpoint atherosclerotic cardiovascular disease (ASCVD) was cardiovascular death, myocardial infarction, ischemic stroke, and coronary revascularization as defined in PROMINENT. ResultsIn the PROMINENT trial, treatment with pemafibrate resulted in -7 mg/dL (−0.18 mmol/L; -18 %) change in remnant cholesterol, +10 mg/dL (+0.26 mmol/L; +12 %) LDL cholesterol, and +5 mg/dL (+0.05 g/L; +5 %) apolipoprotein B. In the CGPS mimicking PROMINENT, the estimated hazard ratios for ASCVD were 0.97 (95 % confidence interval: 0.94–0.99) for a -7 mg/dL (−0.18 mmol/L) change in remnant cholesterol, 1.04 (1.01–1.07) for a +10 mg/dL (+0.26 mmol/L) change in LDL cholesterol, and 1.02 (1.01–1.03) for a +5 mg/dL (+0.05 g/L) change in apolipoprotein B. When combining absolute changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B, the estimated hazard ratio for ASCVD was 1.05 (0.96–1.14) in the CGPS mimicking PROMINENT compared to 1.03 (0.91–1.15) in the PROMINENT trial. ConclusionsAbsolute mass changes in remnant cholesterol, LDL cholesterol, and apolipoprotein B can explain results of the PROMINENT trial. The 3 mg/dL (0.08 mmol/L) higher total atherogenic cholesterol together with 5 mg/dL (0.05 g/L) higher apolipoprotein B seem to explain the trend toward more ASCVD in the pemafibrate arm.

Determination of Pharmacokinetic and Toxicological Parameters of Some Commonly Used Statin Group Drugs

Statins work as inhibitors of the HMG-CoA reductase enzyme and are the most commonly prescribed cholesterol-lowering drug group for people with cardiovascular disease or risk. This study aimed to determine the pharmacokinetic parameters and toxicities of conventional and new-generation cholesterol drugs such as atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin, rosuvastatin and pitavastatin. Absorption, distribution, metabolism, and excretion (ADME) parameters and toxicity predictions of drugs were made using in silico modeling, which gives faster results than animal experiments and does not involve any laboratory costs. In calculations made using structural similarity, compounds' pharmacokinetic properties and toxicity predictions are obtained based on previously known structure-activity data. The study results showed that the toxicity classifications of the drugs were 5 (LD: 5000 mg/kg) for atorvastatin and 6 (LD: 8939 mg/kg) for pravastatin, respectively. The toxicity classes were found to be 4 for all the other statin group drugs. The results showed that pravastatin had the lowest toxicity among investigated cholesterol drugs, while pitavastatin and fluvastatin had the highest toxic effects. Accordingly, it is recommended that the consequences of using pravastatin and atorvastatin, cholesterol drugs with lower toxicity classes, should be investigated more seriously in terms of minimum toxic substance intake for patient groups requiring high doses of medication.

Contemporary hypolipemic therapy: possibilities of novel hypolipemic drugs in correction of lipid metabolism disorders. Review

Dyslipidemia plays a role of significant risk factor for development and progression of cardiovascular diseases. Today several classes of hypolipemic drugs with evidenced effectiveness are used. But some patients don’t tolerate medicines with high efficacy or can’t achieve the targeted blood lipid profile levels even in case of the use of maximal doses or combined therapy. This necessitates the creation of new hypolipidemic agents.
 The review is devoted to discussion of new directions of influence on impaired lipid metabolism through creation of new classes of hypolipemic drugs with some perspectives of effective correction of lipid factors of cardiovascular risk (CVR) in cases of impossibility to achieve the targeted levels of low‑density lipoprotein cholesterol (LDL‑C) or there is a residual CVR caused by elevated serum triglyceride (TG) levels and/or low levels of high‑density lipoprotein cholesterol (HDL‑C).
 Among the novel drugs for hypercholesterolemia (HCE) correction, considerations are given for some mechanisms of action and efficacy of application of proprotein convertase subtilisin‑kexine type 9 (PCSK9) inhibitors as well as bempedoic acid (adenosine triphosphate citrate lyase inhibitor) and inclisiran, a small synthesized interfering ribonucleic acid (RNA) with its ability to blockade genes‑regulators of hepatic PCSK9 activity. The novel agents for hypertriglyceridemia correction, discussed in the review, include icosapent ethyl (a high purified and firm ester of ethyl‑eicosapentoenic acid), pemafibrate (the first selective modulator of α‑receptors activated by peroxisome proliferator), apolipoprotein C‑III (ApoC‑III) inhibitors (volasenorsen, olesarsen), mipomersen (antisense nucleotide for matrix RNA of apolipoprotein B‑100), lomitapide (inhibitor of microsomal TG transfer protein) and inhibitors of angiopoietin‑like protein 3 (ANGPTL3) (evinacumab, vupanorsen). Among the new approaches to HDL‑C elevation an attention is paid to the experimental and clinical investigations of recombinant HDL, agents with recombinant lecithin‑cholesterol‑acyl‑transferase (LCAT), and apolipoprotein A‑I (ApoA‑I) mimetic peptides. For the lowering of blood lipoprotein(a) (LP(a)) level the possibilities of pelacarsen, an antisense oligonucleotide for matrix RNA of apolipoprotein(a) (apo(a)) contained in LP(a) molecule and olpasiran, a small interfering RNA for LP(a) molecule inhibited apo(a) synthesis are uncovered. A high probability of clinical application in the nearest future will have novel drugs approved by US Food and Drug Administration (FDA) and European Medicines Agency (EMA) such as bempedoic acid and inclisiran for HCE correction as well as lomitapide for the treatment of familial HCE.

Antinociception induced by rosuvastatin in mice: Modulation by opioid receptor antagonists, risperidone and l-name

Statins are widely used in cardiovascular disease as cholesterol lowering drugs. However, they also have other actions (pleiotropic effects) including antiproliferative, antithrombotic, neuroprotective, immunomodulatory, anti-inflammatory and antinociceptive activity. The aim of this study was to determine the antinociception properties of rosuvastatin in two murine models of pain and the involvement of opioid antagonists (naltrexone, naltrindole, norbinaltorphimine), risperidone, and L-NAME (L-NG-nitro arginine methyl ester) in this effect. Rosuvastatin was chosen among available statins because it is commonly prescribed and has high potency, efficacy, and an acceptable safety profile. Rosuvastatin antinociception was evaluated in the acetic acid writhing test and the formalin hind paw test by dose-response curves, before and after the i.p. administration of opioid antagonists, risperidone, and L-NAME. This work demonstrates that the assayed drugs modulate the antinociceptive effect of rosuvastatin in both experimental murine pain tests. The antinociception effect described for rosuvastatin may be due to a particular modulation induced by the opioid antagonists, risperidone and L-NAME. Given the broad effects of rosuvastatin, the results of this study may have novel clinical implications in the therapy of pain.

UJI AKTIVITAS ANTIKOLESTEROL EKSTRAK DAUN KETEPENG CINA (Cassia alata L.) TERHADAP PENURUNAN KADAR KOLESTEROL MENCIT PUTIH JANTAN (Mus musculus L.)

High levels of cholesterol in the blood can increase the risk of hypertension, coronary heart disease (CHD), stroke, peripheral artery disease (PAD), and type 2 diabetes. One potential plant for traditional medicine to lower cholesterol levels is Cassia alata L. Cassia alata L. is known to contain flavonoid compounds, suspected to act as cholesterol-lowering agents in the body. This study aimed to determine the anti-cholesterol activity of Cassia alata L. in reducing cholesterol levels in male white mice (Mus musculus L.). The research employed an experimental design, utilizing the maceration method with 96% ethanol as the solvent for extraction. Male white mice aged 3-4 months, weighing 20-30 grams, were used as test subjects. The first group served as the positive control using simvastatin suspension, the second group as the negative control using 0.5% Na CMC solution, the third group received Cassia alata L. extract at a concentration of F1 (10%), F2 (20%), F3 (30%). Data analysis was performed using One Way Anova. The results of the One-way Anova test obtained F count 31.192 > F table 3.48 and sig. value of 0.000 <0.05, so Ho is rejected and Ha is accepted which can be concluded that there is an effect of anticholesterol activity on Cassia alata L. extract. concentration of 10%, 20%, and 30%. Then in the Post Hoc Test using LSD, K (+) showed the same results as F3 (30%) with a significant value of 0.54 so that p>0.05 which showed no significant difference in anticholesterol effectiveness between K (+) and F3 (30%). The results revealed that Cassia alata L. extract at concentrations of 10%, 20%, and 30% exhibited activity in reducing cholesterol levels, which is F3 (30%) demonstrating the most significant cholesterol-lowering effect. This is attributed to the presence of flavonoid compounds in the Cassia alata L. extract.

Abstract 4126: The inhibitory effect of statins on distant metastasis and recurrence of endometrial cancer

Abstract Endometrial cancer (EC) is the most common gynecologic malignancy. The most common histological type is endometrioid endometrial cancer (EEC). While the majority of patients present with early-stage and low-grade EEC and have an excellent prognosis, a subset develops distant recurrence derived from EEC after initial treatment of the primary. However, the exact mechanism of distant metastasis and recurrence from EEC is still unclear. In addition, the lack of suitable pre-clinical models is a significant barrier to research for distant metastasis and recurrent cancer derived from EEC. Our preclinical EEC model, the ablation of both Mig-6 and Pten in the uterus (Pgrcre/+Mig-6f/fPtenf/f; Mig-6d/dPtend/d), dramatically accelerates the development of EEC compared to single ablation of either gene. The ablation of both Mig-6 and Pten in the uterus (Pgrcre/+Mig-6f/f Ptenf/f; Mig-6d/dPtend/d mice) displayed distant metastases into the ovary, diaphragmatic skeletal muscle, lymph node, and lung. However, the Ptend/d mice exhibited endometrial cancer without distant metastases. After hysterectomy of EEC confined to uterus, Mig-6d/dPtend/d mice exhibited recurrent EEC in abdomen and lung. To identify prognostic factors for distant metastatic and recurrent EEC, we performed transcriptomic analysis in endometrial hyperplasia, a precancerous condition, from Ptend/d and Mig-6d/dPtend/d mice. Our transcriptomic analysis identified that cholesterol biosynthesis was the most significantly activated pathway in Mig-6d/dPtend/d mice compared to Ptend/d mice. Statins, also known as HMG-CoA reductase inhibitors, are the most common cholesterol-lowering drugs. We evaluated the effect of atorvastatin on tumorigenesis and recurrence of EEC. Mig-6d/dPtend/d mice treated with atorvastatin displayed significant reduction of tumor size compared to vehicle treated group. For vehicle-treated group, our pathological analysis revealed EEC outside the uterus, therefore EEC had disseminated to involve the ovary, diaphragmatic skeletal muscle, lymph node, and lung. However, EEC was confined to the uterus in the atorvastatin treated group. Furthermore, atorvastatin treatment reduced the rate of recurrent EEC development. This data demonstrated that atorvastatin has a remarkable inhibitory effect on metastasis and recurrence of EEC in Mig-6d/d Ptend/d mice. Our results suggest that statins suppress development of distant metastasis and recurrence in mouse models of EEC with Pten and Mig-6 deficiency by inhibiting cholesterol biosynthesis. Citation Format: Keun Cheon Kim, Jung Yoon Yoo, Russell R Broaddus, Eunhee M Jeong, Mark I Hunter, Tae Hoon Kim, Jae-Wook Jeong. The inhibitory effect of statins on distant metastasis and recurrence of endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4126.

Associations of Digital Ulcers in Patients with Systemic Sclerosis: An 8-Year Retrospective Study

Introduction: This study aimed to investigate the associations of digital ulcers (DUs) in patients with systemic sclerosis (SSc). Methods: This retrospective study investigated the demographic characteristics, specific autoantibodies, organ involvement, and laboratory tests in patients with SSc from our hospital. Results: This study enrolled 144 patients with SSc. The DU+ group consisted of 15 (10.4%) patients. Patients with SSc having DUs have longer disease duration, higher fibrinogen, higher fibrin degradation product, and lower cholesterol. None of the patients used cholesterol-lowering drugs before onset of DUs. The study also demonstrated a higher prevalence of anti-dsDNA and anti-histone antibodies in patients with SSc with DUs. Anti-dsDNA antibody is a specific antibody for SLE with a specificity of 96–99%. A total of 86.1% (124/144) of patients suffered from diffuse cutaneous SSc, and 28.5% (41/144) of patients suffered from overlap syndrome. Conclusion: Our study indicated that patients with SSc with fibrinogen of >2.895 g/L (p = 0.043) and cholesterol of <3.340 mmol/L (p = 0.036), which is equal to 129.258 mg/dL, are at high risk of developing DUs.

Repurposing of the Cardiovascular Drug Statin for the Treatment of Cancers: Efficacy of Statin-Dipyridamole Combination Treatment in Melanoma Cell Lines.

Metastatic melanoma has a very poor prognosis. Statins, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) inhibitors, are cholesterol-lowering agents with a potential for cancer treatment. The inhibition of HMGCR by statins, however, induces feedback, which paradoxically upregulates HMGCR expression via sterol regulatory element-binding protein-2 (SREBP2). Dipyridamole, an antiplatelet agent, is known to inhibit SREBP2 upregulation. We aimed to demonstrate the efficacy of statin-dipyridamole combination treatment in both human and spontaneously occurring canine melanoma cell lines. The half maximal inhibitory concentration (IC50) of atorvastatin showed a 68-92% reduction when combined with dipyridamole, compared with that of atorvastatin alone. In some melanoma cell lines, cell proliferation was suppressed to almost zero by the combination treatment (≥3 μM atorvastatin). Finally, the BRAF inhibitor, vemurafenib, further potentiated the effects of the combined statin-dipyridamole treatment in BRAF V600E mutation-bearing human melanoma cell lines. In conclusion, the inexpensive and frequently prescribed statin-dipyridamole combination therapy may lead to new developments in the treatment of melanoma and may potentiate the effects of vemurafenib for the targeted therapy of BRAF V600E-mutation bearing melanoma patients. The concordance between the data from canine and human melanoma cell lines reinforces this possibility.

Magnesium-oxide-enhanced bone regeneration: 3D-printing of gelatin-coated composite scaffolds with sustained Rosuvastatin release

Critical-size bone defects are one of the main challenges in bone tissue regeneration that determines the need to use angiogenic and osteogenic agents. Rosuvastatin (RSV) is a class of cholesterol-lowering drugs with osteogenic potential. Magnesium oxide (MgO) is an angiogenesis component affecting apatite formation. This study aims to evaluate 3D-printed Polycaprolactone/β-tricalcium phosphate/nano-hydroxyapatite/ MgO (PCL/β-TCP/nHA/MgO) scaffolds as a carrier for MgO and RSV in bone regeneration. For this purpose, PCL/β-TCP/nHA/MgO scaffolds were fabricated with a 3D-printing method and coated with gelatin and RSV. The biocompatibility and osteogenicity of scaffolds were examined with MTT, ALP, and Alizarin red staining. Finally, the scaffolds were implanted in a bone defect of rat's calvaria, and tissue regeneration was investigated after 3 months. Our results showed that the simultaneous presence of RSV and MgO improved biocompatibility, wettability, degradation rate, and ALP activity but decreased mechanical strength. PCL/β-TCP/nHA/MgO/gelatin-RSV scaffolds produced sustained release of MgO and RSV within 30 days. CT images showed that PCL/β-TCP/nHA/MgO/gelatin-RSV scaffolds filled approximately 86.83 + 4.9 % of the defects within 3 months and improved angiogenesis, woven bone, and osteogenic genes expression. These results indicate the potential of PCL/β-TCP/nHA/MgO/gelatin-RSV scaffolds as a promising tool for bone regeneration and clinical trials.

The evolution of the gliotoxin biosynthetic gene cluster in Penicillium fungi.

Fungi biosynthesize diverse secondary metabolites, small organic bioactive molecules with key roles in fungal ecology. Fungal secondary metabolites are often encoded by physically clustered genes known as biosynthetic gene clusters (BGCs). Fungi in the genus Penicillium produce a cadre of secondary metabolites, some of which are useful (e.g. the antibiotic penicillin and the cholesterol-lowering drug mevastatin) and others harmful (e.g. the mycotoxin patulin and the immunosuppressant gliotoxin) to human affairs. Fungal genomes often also encode resistance genes that confer protection against toxic secondary metabolites. Some Penicillium species, such as Penicillium decumbens, are known to produce gliotoxin, a secondary metabolite with known immunosuppressant activity. To investigate the evolutionary conservation of homologs of the gliotoxin BGC and of genes involved in gliotoxin resistance in Penicillium, we analyzed 35 Penicillium genomes from 23 species. Homologous, lesser fragmented gliotoxin BGCs were found in 12 genomes, mostly fragmented remnants of the gliotoxin BGC were found in 21 genomes, whereas the remaining 2 Penicillium genomes lacked the gliotoxin BGC altogether. In contrast, broad conservation of homologs of resistance genes that reside outside the BGC across Penicillium genomes was observed. Evolutionary rate analysis revealed that BGCs with higher numbers of genes evolve slower than BGCs with few genes, suggestive of constraint and potential functional significance or more recent decay. Gene tree-species tree reconciliation analyses suggested that the history of homologs in the gliotoxin BGC across the genus Penicillium likely involved multiple duplications, losses, and horizontal gene transfers. Our analyses suggest that genes encoded in BGCs can have complex evolutionary histories and be retained in genomes long after the loss of secondary metabolite biosynthesis.

The effects of cholesterol and statins on Parkinson's neuropathology: a narrative review.

Parkinson disease (PD) is chronic and progressive neurodegenerative disease of the brain characterized by motor symptoms including tremors, rigidity, postural instability, and bradykinesia. PD neuropathology is due to the progressive degeneration of dopaminergic neurons in the substantia nigra and accumulation of Lewy bodies in the survival neurons. The brain contains a largest amount of cholesterol which is mainly synthesized from astrocytes and glial cells. Cholesterol is intricate in the pathogenesis of PD and may be beneficial or deleterious. Therefore, there are controversial points concerning the role of cholesterol in PD neuropathology. In addition, cholesterol-lowering agents' statins can affect brain cholesterol. Different studies highlighted that statins, via inhibition of brain HMG-CoA, can affect neuronal integrity through suppression of neuronal cholesterol, which regulates synaptic plasticity and neurotransmitter release. Furthermore, statins affect the development and progression of different neurodegenerative diseases in bidirectional ways that could be beneficial or detrimental. Therefore, the objective of the present review was to clarify the double-sward effects of cholesterol and statins on PD neuropathology.

Histopatologi Hepar Tikus Dengan Induksi Pakan Tinggi Lemak Setelah Pemberian Biji Mahoni

High accumulation of lipids in hepatocytes can trigger an increase in the production of radical compounds, leading to fatty liver disease. This condition induces histological changes in the liver, especially in hepatocytes, and affects the surrounding structures. Mahogany seeds have the potential to act as a hypolipidemic agent in treating fatty liver. Mahogany seeds are known to contain phytochemical compounds which act as antioxidants. This study aimed to determine liver histopathology of rats by inducing high-fat diet after giving mahogany seeds ethanol extract which was observed through the percentage of steatosis, hepatocyte diameter, and hepatosomatic index. This study involved thirty male Sprague Dawley rats, divided into 6 groups: P0 (given commercial feed), P1 (given high-fat diet), P2 (given high-fat diet and simvastatin at a dose of 8 mg/200 g BW), P3, P4, and P5 (given high-fat diet and mahogany seeds ethanol extract at a dose of 14, 28, and 56 mg/200 g BW). The results showed that the hepatosomatic index among all treatment groups did not differ significantly; however, the percentage of steatosis and hepatocyte diameter in the groups given mahogany seeds ethanol extract significantly differed from the group given only high-fat feed. Based on these results, it can be concluded that mahogany seed ethanol extract can maintain the histological structure of the liver in male Sprague Dawley rats with fatty liver. Keywords: hepatocyte, hepatosomatic index, high-fat diet, mahogany seeds, steatosis

Carbohydrazide-Based schiff bases for selective Hg (II) ion sensing and computational analysis of cholesterol lowering activity

The presence of mercury ion (Hg (II)) in the environment is a serious health concern. Therefore, it is essential to measure and monitor the levels of Hg (II) in the environment to safeguard public health. This study focuses on the synthesis of carbohydrazide-based Schiff bases (4–5) and exhibit a red-shift in absorption upon addition of Hg (II) ion, making them highly selective and sensitive in detecting Hg (II). The confirmation of the synthesized compounds was achieved using (1H and 13C) NMR spectroscopy and mass spectrometry. Additionally, the detection limits towards Hg (II) were determined to be 7.56 × 10-7 M and 1.42 × 10-6 M for compounds 4 and 5, respectively. The 1H NMR spectra provided evidence of interactions between compounds 4–5 and Hg (II) ion. The compounds 4 and 5 were evaluated for Bioactivity, Drug likeness parameters and Prediction of Activity Spectra (PASS) analysis to design a new molecule with a favorable pharmacological profile. Based on the PASS results, molecular docking studies of compounds 4 and 5 were performed with Cholesteryl Ester Transfer Protein (CETP) (PDB ID: 2OBD), revealing inhibitory activity. These findings suggest the potential of these compounds as candidates for antihyperlipidemic or cholesterol-lowering agents.

A Retrospective Study: The Effectiveness of Lipid-Lowering Medications in Individuals at High Risk for Cardiovascular Disease

Objective: The effective administration of lipid-lowering treatment is of utmost importance in mitigating cardiovascular (CV) risk in patients who are undergoing secondary prevention. High-dose statins, ezetimibe, and the relatively newer PCSK9 inhibitors (PCSK9i) have shown effectiveness in achieving low density lipoprotein cholesterol(LDL-C) treatment targets for these patients. However, despite substantial evidence supporting their efficacy, these interventions remain significantly underutilized, primarily due to poor levels of patient adherence. Moreover, there is limited data available on the overall effectiveness of cholesterol-lowering treatment and the proportion of secondary prevention patients who have achieved a well-regulated lipid profile. In light of these factors, the principal aim of this investigation was to evaluate the present status of lipid-lowering medication within this specific group of individuals. Methods: The study was conducted at Mardin Artuklu University, Mardin Training and Research Hospital between April 2021 and March 2023, focusing on patients with a history of secondary prevention of CVD. The study investigated prescribed cholesterol-lowering drugs, factors contributing to statin underuse, and lipid profile disclosure. Results: 872 patients were included. 86.8% received statins, 5.2% ezetimibe, and 3.4% fibrates, while 13.2% received no lipid-lowering therapy. 64% of those on statins were on high doses. LDL-C values were assessed in 452 patients, with only 30% below the recommended cutoff of 70 mg/dL. Conclusion: In this investigation involving secondary prevention patients, slightly over half of the participants received high-dose statins, while a negligible proportion received ezetimibe treatment. Alarmingly, over two-thirds of the patients demonstrated LDL-C values that deviated significantly from the therapeutic range, indicating a considerable gap between their lipid profiles and the recommendations set forth by clinical guidelines.

Selected widely prescribed pharmaceuticals: toxicity of the drugs and the products of their photochemical degradation to aquatic organisms.

Cholesterol-lowering drugs, antidiabetics, antiarrhythmics, antidepressants, and antibiotics belong to the most prescribed drugs worldwide. Because of the manufacture, excretion, and improper disposal of leftover drugs, the drugs enter waste waters and, subsequently, surface waters. They have been detected in surface waters all over the world, from concentrations of ng/l to concentrations several orders of magnitude higher. Since pharmaceuticals are designed to be both biologically and chemically stable, photochemical degradation by sun radiation represents a way of transformation in the natural environment. This review provides a survey of how selected drugs of the above-mentioned classes affect aquatic organisms of different trophic level. The emphasis is on the harmful effects of phototransformation products, an area of scientific investigation that has only attracted attention in the past few years, revealing the surprising fact that products of photochemical degradation might be even more toxic to aquatic organisms than the parent drugs.

Aldo-keto reductase-7A2 protects against atorvastatin-induced hepatotoxicity via Nrf2 activation

Atorvastatin (ATO), as a cholesterol-lowering drug, was the world's best-selling drug in the early 2000s. However, ATO overdose-induced liver or muscle injury is a threat to many patients, which restricts its application. Previous studies suggest that ATO overdose is accompanied with ROS accumulation and increased lipid peroxidation, which are the leading causes of ATO-induced liver damage. This study is, therefore, carried out to investigate the roles of anti-oxidant pathways and enzymes in protection against ATO-induced hepatotoxicity. Here we show that in ATO-challenged HepG2 cells, the expression levels of transcription factor NFE2L2/Nrf2 (nuclear factor erythroid 2 p45-related factor 2) are significantly upregulated. When Nrf2 is pharmacologically inhibited or genetically inactivated, ATO-induced cytotoxicity is significantly aggravated. Aldo-keto reductase-7A (AKR7A) enzymes, transcriptionally regulated by Nrf2, are important for bioactivation and biodetoxification. Here, we reveal that in response to ATO exposure, mRNA levels of human AKR7A2 are significantly upregulated in HepG2 cells. Furthermore, knockdown of AKR7A2 exacerbates ATO-induced hepatotoxicity, suggesting that AKR7A2 is essential for cellular adaptive response to ATO-induced cell damage. In addition, overexpression of AKR7A2 in HepG2 cells can significantly mitigate ATO-induced cytotoxicity and this process is Nrf2-dependent. Taken together, these findings indicate that Nrf2-mediated AKR7A2 is responsive to high concentrations of ATO and contributes to protection against ATO-induced hepatotoxicity, making it a good candidate for mitigating ATO-induced side effects.

Anti-diabetic effect of &lt;i&gt;Eucalyptus camaldulensis&lt;/i&gt; (Red gum) leaf-supplemented diet in streptozotocin-induced diabetic rats

Purpose: To investigate the potential anti-diabetic effect of supplementing a diet with Eucalyptus camaldulensis leaves in streptozotocin (STZ) induced Wistar rats. &#x0D; Methods: Methanolic extract of E. camaldulensis was screened using gas chromatography-mass spectrometric analysis. After that, eighteen animals were separated into three groups: Group A served as control group. Group B, the diabetic control group, was induced with STZ, and Group C was induced with STZ and fed a 10 % E. camaldulensis leaf-supplemented diet for 14 days. Thereafter, rats were sacrificed, and fasting blood was collected for serum glucose, enzyme and protein activity tests. Organs were excised for biochemical and histological analysis. &#x0D; Results: The GC-MS fingerprint identified 17 constituents, with 2-hydroxy carbazole being the most abundant. Rats on the E. camaldulensis leaf-based diet for 14 days exhibited a significant decrease (p &lt; 0.05) in serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), amylase, albumin, total bilirubin, urea, and creatinine concentrations compared to diabetic controls. Insulin levels significantly increased (p &lt; 0.05). Additionally, the E. camaldulensis diet led to a significant decrease in serum lipid profile levels but increased high-density lipoprotein cholesterol (HDL-C). Superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities increased significantly, while malondialdehyde levels decreased significantly (p &lt; 0.05). Histopathology revealed positive effects on hepatocytes, acini, pancreatic duodenal lymphoid activation, islets of Langerhans resurgence, and normal kidneys. &#x0D; Conclusion: Eucalyptus camaldulensis leaf-supplemented diet demonstrates anti-diabetic, hypolipidemic and antioxidant enzyme activities. Carbazole identified by GC-MS may be the potential anti-diabetic and hypolipidemic agent in E. camaldulensis leaf-based diet.