BMC Pharmacology & Toxicology最新文献

{"title":"Effects of melatonin on the prevention of delirium in hospitalized older patients: systematic review and meta-analysis.","authors":"Le Liu, Xin Ma, Zejun Song, Jie Li, Yasong Zhao, Chang Meng, Shufang Wang, Guobin Miao, Peng Liu","doi":"10.1186/s40360-024-00816-9","DOIUrl":"10.1186/s40360-024-00816-9","url":null,"abstract":"<p><strong>Objectives: </strong>Melatonin has been demonstrated to exert a preventive effect on delirium. This meta-analysis sought to investigate the preventive effects of melatonin and melatonin receptor agonists (ramelteon) on delirium in hospitalized elderly patients.</p><p><strong>Methods: </strong>This systematic review and meta-analysis delineates the risk of delirium events in older hospitalized patients with melatonin/ramelteon compared with placebo, incorporating randomized controlled trials published up to 8 July 2024. The databases searched were PubMed, Embase and the Cochrane Library. The primary outcome measures were the incidence of delirium, while the secondary outcome measures were the length of hospital stay and mortality. The results are presented as odds ratios (OR) or mean differences (MD) with a 95% confidence interval. The review of publications was conducted in accordance with the guidelines set forth in the Cochrane Handbook and the Preferred Reporting Project for Systematic Review and Meta-Analysis (PRISMA). This study has been registered with INPLASY (number INPLASY202470044).</p><p><strong>Results: </strong>A total of 2086 patients were included in 13 randomized controlled trials. The primary outcome of this meta-analysis demonstrated a statistically difference in the incidence of delirium between the melatonin and placebo groups in hospitalized elderly patients (OR = 0.59, 95% CI: 0.40-0.87, P < 0.01, I² = 60%), particularly in those who had undergone surgery (OR = 0.60, 95%CI: 0.40-0.89, P = 0.01, I² = 53%). No statistically differences were observed in terms of length of stay (MD=-0.07, 95%CI:-1.09-0.94, P = 0.89, I² = 72%) and mortality (OR = 0.79, 95%CI:0.58-1.06, P = 0.12, I² = 0%).</p><p><strong>Conclusions: </strong>Melatonin has been demonstrated to exert a protective effect on delirium in elderly patients who are hospitalized, particularly in the context of perioperative care.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"90"},"PeriodicalIF":2.8,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587658/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142715061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pulrodemstat, a selective inhibitor of KDM1A, suppresses head and neck squamous cell carcinoma growth by triggering apoptosis.","authors":"Cheng Jiang, Xiaofeng Weng, Yuqing Chen, Junjun Yang","doi":"10.1186/s40360-024-00807-w","DOIUrl":"10.1186/s40360-024-00807-w","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy is often ineffective as a first-line treatment for head and neck squamous cell carcinoma (HNSCC), and a more precise and effective therapeutic option is urgently needed.</p><p><strong>Methods: </strong>High-throughput screening of a histone demethylase inhibitor library was performed to identify potential drugs for treating HNSCC. The Cancer Genome Atlas (TCGA) and single-cell sequencing were used to evaluate the potential diagnostic value and expression distribution of candidate drug targets. Colony formation, transwell assays, and flow cytometry analyses were used to assess the antitumor function of the potential drugs. The CCK-8 assay was used to compare the antitumor activity of the candidate drug and the traditional chemotherapy drug. Bioinformatic analysis based on TCGA database was used for unveiling the upstream signaling.</p><p><strong>Results: </strong>Pulrodemstat, a selective KDM1A inhibitor that is ongoing clinical trial, stood out as the most effective candidate anti-HNSCC drug based on the high-throughput screening. IC₅₀ analysis revealed that Pulrodemstat might possess stronger anti-tumor activity than 5-Fu. Additionally, Pulrodemstat dramatically suppressed HNSCC cell proliferation and migration without inducing toxicity in normal cells. TCGA analysis revealed that KDM1A is positively associated with tumor proliferation, DNA repair, and DNA replication in HNSCC. Consistent with these results, Pulrodemstat substantially induced apoptosis in the HNSCC cells. Furthermore, TCGA analysis revealed that KDM1A was aberrantly overexpressed in HNSCC, positively correlated with malignancy, and negatively associated with the clinical outcomes of HNSCC patients. Notably, single-cell analysis indicated that KDM1A was mainly distributed in the malignant cells of HNSCC samples, highlighting that Pulrodemstat may be a more precise therapeutic option for HNSCC. In addition, methylation occupancies in the KDM1A promoter were substantially low in HNCC tumors, and low methylation occupancies in the KDM1A promoter predicted poor clinical outcomes in HNSCC. These data are consistent with the KDM1A expression in HNSCC. Moreover, TET3, a DNA demethylase, was strongly and positively correlated with KDM1A expression.</p><p><strong>Conclusions: </strong>Pulrodemstat is an effective therapeutic drug for HNSCC. Thus, the TET3/KDM1A axis may account for the malignant phenotype of HNSCC.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"89"},"PeriodicalIF":2.8,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol inhibits ferroptosis in the lung tissues of heat stroke-induced rats via the Nrf2 pathway.","authors":"Liwen Du, Xueqi Zhu, Zhenluo Jiang, Weidong Wang, Peng Liu, Leilei Zhu, Fangqi Zhang","doi":"10.1186/s40360-024-00810-1","DOIUrl":"10.1186/s40360-024-00810-1","url":null,"abstract":"<p><strong>Background: </strong>Heat stroke (HS) can lead to the development of pulmonary ferroptosis. The inhibition of pulmonary ferroptosis during HS improves patient prognosis. The aim of this study was to investigate the effects of resveratrol (RES) on heat stress at an ambient temperature of 42 °C.</p><p><strong>Methods: </strong>Heat stress was induced in Beas-2B cells and lung injury was induced in HS rats at an ambient temperature of 42 °C. The anti-oxidative stress and anti-ferroptotic effects of RES were confirmed through tail vein injection of nuclear factor-2 associated factor (Nrf2) shRNA recombinant adeno-associated virus 6 (AAV6-shNrf2).</p><p><strong>Results: </strong>RES treatment attenuated the upregulation of reactive oxygen species (ROS) and malondialdehyde (MDA) levels and alleviated glutathione inhibition in HS. In addition, RES treatment reduced the accumulation of Fe²⁺ in heat-stressed Beas-2B cells and increased the ferroptosis resistance-related proteins FTH1, GPX4, and SLC7A11 as well as the anti-oxidative stress pathway proteins Nrf2, NQO1, and HO-1. The antioxidant and anti-ferroptotic effects of RES in heat-stressed Beas-2B cells were effectively reversed upon treatment with Nrf2-IN-1, an Nrf2 pathway inhibitor. In the HS rat model, the antioxidant and anti-ferroptotic effects of RES were reversed by an ambient temperature of 42 °C and relative humidity of 60 ± 5%.</p><p><strong>Conclusions: </strong>RES effectively protected HS rats from lung injury, inhibited the accumulation of Fe²⁺, ROS, and MDA in the lung, and upregulated FTH1, GPX4, SLC7A11, Nrf2, NQO1, and HO-1.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"88"},"PeriodicalIF":2.8,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11577854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An in vivo and in silico probing of the protective potential of betaine against sodium fluoride-induced neurotoxicity.","authors":"Solomon E Owumi, Bayode J Oluwawibe, Joseph Chimezie, Jesutosin J Babalola, Oludare M Ogunyemi, Gideon A Gyebi, Moses T Otunla, Ahmad Altayyar, Uche O Arunsi, Chioma E Irozuru, Olatunde O Owoeye","doi":"10.1186/s40360-024-00812-z","DOIUrl":"10.1186/s40360-024-00812-z","url":null,"abstract":"<p><p>Excessive fluoride exposure beyond the tolerable limit may adversely impacts brain functionality. Betaine (BET), a trimethyl glycine, possesses antioxidant, anti-inflammatory and anti-apoptotic functions, although the underlying mechanisms of the role of BET on fluoride-induced neurotoxicity remain unelucidated. To assess the mechanism involved in the neuro-restorative role of BET on behavioural, neurochemical, and histological changes, we employed a rat model of sodium fluoride (NaF) exposure. Animals were treated with NaF (9 mg/kg) body weight (bw) only or co-treated with BET (50 and 100 mg/kg bw) orally uninterrupted for 28 days. We obtained behavioural phenotypes in an open field, performed negative geotaxis, and a forelimb grip test, followed by oxido-inflammatory, apoptotic, and histological assessment. Behavioural endpoints indicated lessened locomotive and motor and heightened anxiety-like performance and upregulated oxidative, inflammatory, and apoptotic biomarkers in NaF-exposed rats. Co-treatment with BET significantly enhanced locomotive, motor, and anxiolytic performance, increased the antioxidant signalling mechanisms and demurred oxidative, inflammatory, and apoptotic biomarkers and histoarchitectural damage in the cerebrum and cerebellum cortices mediated by NaF. The in-silico analysis suggests that multiple hydrogen bonds and hydrophobic interactions of BET with critical amino acid residues, including arginine (ARG380 and ARG415) in the Keap1 Kelch domain, which may disrupt Keap1-Nrf2 complex and activate Nrf2. This may account for the observed increased in the Nrf2 levels, elevated antioxidant response and enhanced anti-inflammatory response. The BET-Keap1 complex was also observed to exhibit structural stability and conformational flexibility in solvated biomolecular systems, as indicated by the thermodynamic parameters computed from the trajectories obtained from a 100 ns full atomistic molecular dynamics simulation. Therefore, BET mediates neuroprotection against NaF-induced cerebro-cerebellar damage through rats' antioxidant, anti-inflammatory, and anti-apoptotic activity, which molecular interactions with Keap1-Nrf2 may drive.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"87"},"PeriodicalIF":2.8,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cinnamaldehyde ameliorates diabetes-induced biochemical impairments and AGEs macromolecules in a pre-clinical model of diabetic nephropathy.","authors":"Noor Fatima, M Israr Khan, Hira Jawed, Urooj Qureshi, Zaheer Ul-Haq, Rahman M Hafizur, Tawaf Ali Shah, Musaab Dauelbait, Yousef A Bin Jardan, Gamal A Shazly","doi":"10.1186/s40360-024-00811-0","DOIUrl":"10.1186/s40360-024-00811-0","url":null,"abstract":"<p><strong>Purpose: </strong>Cinnamaldehyde, has various therapeutic potentials including glucose-lowering effect, and insulinotropic effect; however, its glycation inhibitory mechanism is not known yet. In this study, we explored the effects of cinnamaldehyde for its AGEs inhibitory mechanism in a streptozotocin-complete Freund's adjuvant (STZ-CFA) induced diabetic nephropathy (DN) rat model.</p><p><strong>Methods: </strong>Pre-clinical DN model was developed by the administration of multiple low doses of STZ-CFA in rats, mainly characterized by abnormal blood parameters and nephrotic damages. Diabetes-related systemic profile and histopathological hallmarks were evaluated using biochemical assays, microscopic imaging, immunoblot, and real-time PCR analyses, supported by cinnamaldehyde-albumin interaction assessed using STD-NMR and in silico site-directed interactions in the presence of glucose.</p><p><strong>Results: </strong>Cinnamaldehyde-treatment significantly reversed DN hallmarks, fasting blood glucose (FBG), serum insulin, glycated hemoglobin (HbA1c), urinary microalbumin, and creatinine contrasted to non-treated DN rats and aminoguanidine, a positive reference advanced glycation end products (AGEs) inhibitor. The pathological depositions of AGEs, receptor for advanced glycation end products (RAGE), and carboxymethyl lysine (CML), and transcriptional levels of AGE-RAGE targeted immunomodulatory factors (IL1β, TNF-α, NF-κB, TGF-β) were significantly improved in cinnamaldehyde treated rats as compared to aminoguanidine. Cinnamaldehyde post-treatment improved pancreatic pathology and systemic glycemic index (0.539 ± 0.01 vs. 0.040 ± 0.001, P < 0.001) in DN rats. Subsequently, in silico profiling of cinnamaldehyde defined the competitive binding inhibition with glucose in AGE and RAGE receptors that was further confirmed by in vitro STD-NMR analysis.</p><p><strong>Conclusion: </strong>These findings suggest potential role of cinnamaldehyde in reversing STZ-induced diabetic nephropathic impairments; therefore, appears promising candidate for further pharmacological explorations towards diabetes-associated complications.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"85"},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world research on beta-blocker usage trends in China and safety exploration based on the FDA Adverse Event Reporting System (FAERS).","authors":"Yilong Yan, Wenshuo An, Shenghui Mei, Qiang Zhu, Cao Li, Li Yang, Zhigang Zhao, Jiping Huo","doi":"10.1186/s40360-024-00815-w","DOIUrl":"10.1186/s40360-024-00815-w","url":null,"abstract":"<p><strong>Background: </strong>Beta-blockers are widely used, with continuously updated clinical recommendations. However, their application faces challenges in personalized treatment and safety. The study aimed to investigate the frequency and patterns of prescribing beta-blockers in China and to explore potential adverse event risk signals associated with beta-blockers, providing reference for rational medication use in clinical settings.</p><p><strong>Methods: </strong>Prescription data for beta-blockers from January 2018 to June 2023 were extracted through the Hospital Prescription Analysis Collaborative Project in China to analyze clinical usage trends. While adverse drug reaction reports for beta-blockers were obtained from the FDA Adverse Event Reporting System (FAERS) database. The classification and standardization of adverse drug event (ADE) reports were based on the preferred terms (PT) and corresponding system organ classes (SOC) from the Medical Dictionary for Regulatory Activities (MedDRA). Signal detection utilized a proportion imbalance method.</p><p><strong>Results: </strong>In clinical practice, metoprolol dominated beta-blocker prescriptions in China, accounting for 62.2%. Beta-blockers were primarily prescribed to the elderly (65.7%) and male patients (57.0%). However, off-label use of beta-blockers was relatively widespread. For instance, sotalol was prescribed for hypertension at 18.25%, while esmolol was used for angina and heart failure at rates of 12.94% and 14.98%, respectively. In addition, we identified newly discovered adverse reactions associated with beta-blockers, such as BRASH syndrome (metoprolol: n = 186, ROR = 391.285; carvedilol: n = 72, ROR = 256.459), acute kidney injury (bisoprolol: n = 247, ROR = 5.641), premature baby (labetalol: n = 110, ROR = 91.385), and sleep disorder (propranolol: n = 254, ROR = 10.98).</p><p><strong>Conclusions: </strong>Metoprolol led the beta-blocker market in China. Attention was warranted regarding the newly discovered adverse reactions, such as the risk of acute kidney injury with bisoprolol and the potential for BRASH syndrome with metoprolol and carvedilol.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"86"},"PeriodicalIF":2.8,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11566443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Drug risks associated with sarcopenia: a real-world and GWAS study.","authors":"Zhaoliang Zhang, Liehui Yao","doi":"10.1186/s40360-024-00813-y","DOIUrl":"10.1186/s40360-024-00813-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Drug-induced sarcopenia has not received adequate attention. Meanwhile, there is growing recognition of the importance of effective pharmacovigilance in evaluating the benefits and risks of medications.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;The primary aim of this study is to investigate the potential association between drug use and sarcopenia through an analysis of adverse event reports from the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) and to evaluate the genetic factors contributing to drug-induced sarcopenia using summary-data-based Mendelian randomization (SMR).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We obtained reports of adverse drug reactions from FAERS. Primary outcomes included sarcopenia and potential sarcopenia. We calculated the Proportional reporting ratio (PRR) to assess the risk of specific adverse events associated with various drugs, applying chi-square tests for statistical significance. Additionally, we used SMR based on Genome-wide association study (GWAS) to evaluate the potential associations between drug target genes of some significant medications and sarcopenia outcomes. The outcome data for sarcopenia included metrics as hand grip strength and appendicular lean mass (ALM).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 55 drugs were identified as inducing potential sarcopenia, and 3 drugs were identified as inducing sarcopenia. The top 5 drugs causing a potential risk of sarcopenia were levofloxacin (PRR = 9.96, χ&lt;sup&gt;2&lt;/sup&gt; = 1057), pregabalin (PRR = 7.20, χ&lt;sup&gt;2&lt;/sup&gt; = 1023), atorvastatin (PRR = 4.68, χ&lt;sup&gt;2&lt;/sup&gt; = 903), duloxetine (PRR = 4.76, χ&lt;sup&gt;2&lt;/sup&gt; = 527) and venlafaxine (PRR = 5.56, χ&lt;sup&gt;2&lt;/sup&gt; = 504), and the 3 drugs that had been proved to induced sarcopenia included metformin (PRR = 7.41, χ&lt;sup&gt;2&lt;/sup&gt; = 58), aspirin (PRR = 5.93, χ&lt;sup&gt;2&lt;/sup&gt; = 35), and acetaminophen (PRR = 4.73, χ&lt;sup&gt;2&lt;/sup&gt; = 25). We identified electron-transfer flavoprotein dehydrogenase (ETFDH) and protein Kinase AMP-Activated Non-Catalytic Subunit Beta 1 (PRKAB1) as the primary drug target genes for metformin, while Prostaglandin-endoperoxide Synthase 1 (PTGS1) and Prostaglandin-endoperoxide Synthase 2 (PTGS2) were considered the primary action target genes for aspirin and acetaminophen according to DrugBank database. SMR showed that the expression abundance of ETFDH was negatively correlated with right hand grip strength (blood: OR = 1.01, p-value = 1.27e-02; muscle: OR = 1.01, p-value = 1.42e-02) and negatively correlated with appendicular lean mass (blood: OR = 1.03, p-value = 7.73e-08; muscle: OR = 1.03, p-value = 1.67e-07).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;We find that metformin, aspirin, and acetaminophen are specifically noted for their potential to induce sarcopenia based on the analyses conducted. We perform signal mining for drug-associated sarcopenia events based on real-world data and provides certain guidance for the safe use of medications to prevent sarcopenia","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"84"},"PeriodicalIF":2.8,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic profile of novel multi-layer stable effervescent tablet: a cross-over study with an established European brand in healthy young male adults.","authors":"Danish Hassan Dani, Syed Baqir Shyum Naqvi, Muhammad Akram, Matti Ullah, Sheikh Abdul Khaliq, Muhammad Masoom Akhtar, Orva Abdullah, Syed Faisal Badshah, Mohammed Bourhia, Gamal A Shazly, Yousef A Bin Jardan, Srosh Fazil","doi":"10.1186/s40360-024-00808-9","DOIUrl":"10.1186/s40360-024-00808-9","url":null,"abstract":"<p><p>Effervescent formulation helps in faster and better absorption of drugs, especially those that are rapidly soluble in water. However, these tablets require special packaging in order to prevent them from absorbing moisture, hence increasing cost. We compared an effervescent tablet prepared using an in-house developed method (multi-layer tablet with acid and base part separated by an inert layer) to a European effervescent tablet (Efferalgan®) in a single-center, randomized cross-over study among twelve healthy volunteers. Blood samples were collected for 8 h and analyzed for paracetamol concentration using HPLC. Our results showed that both the products have similar pharmacokinetic profiles with no significant difference observed for C_last, T_half, K_elim, and MRT (p-value > 0.05). Moreover, to assess bioequivalence we did not find any significant difference (p-value > 0.05) in AUC (27.12 ± 6.02 vs. 27.29 ± 2.64 µg.h/ml), C_max (7.42 ± 1.06 vs. 7.83 ± 1.19 µg/ml) and t_max (0.85 ± 0.22 vs. 0.83 ± 0.25 h). The TR ratios for AUC, C_max, and t_max were 0.99, 0.95, and 1.02 respectively, and were all within the specified FDA limits i.e., 0.8-1.25. We found our test tablet to be bioequivalent to that of Efferalgan®.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"83"},"PeriodicalIF":2.8,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536717/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephroprotective role of resveratrol in renal ischemia-reperfusion injury: a preclinical study in Sprague-Dawley rats.","authors":"Elaf R Alaasam, Ali M Janabi, Karrar M Al-Buthabhak, Rihab H Almudhafar, Najah R Hadi, Athanasios Alexiou, Marios Papadakis, Mohammed E Abo-El Fetoh, Dalia Fouad, Gaber El-Saber Batiha","doi":"10.1186/s40360-024-00809-8","DOIUrl":"10.1186/s40360-024-00809-8","url":null,"abstract":"<p><strong>Background: </strong>Renal ischemia-reperfusion injury (IRI) is a significant contributor to renal dysfunction, acute kidney injury (AKI), and associated morbidity and mortality. Resveratrol, a polyphenol and phytoalexin, is known for its anti-inflammatory, antioxidant, and anti-cancer properties. This study investigates the nephroprotective potential of resveratrol in a rat model of renal IRI.</p><p><strong>Materials and methods: </strong>Twenty-eight male Sprague-Dawley rats were divided into four groups: Sham, IRI, DMSO, and Resveratrol. The Sham group underwent identical procedures without renal pedicle clamping, while the IRI group experienced 30 min of ischemia followed by 2 h of reperfusion. The DMSO group received dimethyl sulfoxide (DMSO) intraperitoneally 30 min before ischemia, and the Resveratrol group received 30 mg/kg resveratrol intraperitoneally 30 min before ischemia. Biochemical parameters (Urea, creatinine, IL-1β, NF-κβ, SOD, GSH, Bcl-2, and caspase-3) and histopathological changes were assessed.</p><p><strong>Results: </strong>IRI caused a substantial increase in serum creatinine, Urea, IL-1β, NF-κβ, and caspase-3 levels, while simultaneously decreasing SOD, GSH, and Bcl-2 levels. Resveratrol treatment mitigated these effects by lowering inflammatory and apoptotic markers, enhancing antioxidant defenses, and improving histological outcomes.</p><p><strong>Conclusion: </strong>Resveratrol demonstrates significant nephroprotective effects in renal IRI, primarily through its antioxidant, anti-inflammatory, and anti-apoptotic properties.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"82"},"PeriodicalIF":2.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11520524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postoperative opioid use in Norway-a population-based observational study on patterns of long-term use.","authors":"Sara Magelssen Vambheim, Vidar Hjellvik, Ingvild Odsbu, Svetlana Skurtveit, Christopher Ekholdt, Lars Petter Granan, Audun Stubhaug, Per-Jostein Samuelsen","doi":"10.1186/s40360-024-00805-y","DOIUrl":"10.1186/s40360-024-00805-y","url":null,"abstract":"<p><strong>Background: </strong>The utilization patterns of opioid analgesics and the proportion of long-term opioid use after surgery in Norway is largely unknown.</p><p><strong>Methods: </strong>This study aimed to estimate the proportion of one-year long-term prescription opioid use among all Norwegian postoperative opioid users. Complete data from central health registries (NPR, NorPD, Statistics Norway, CoDR) were linked via the personal identification number unique to all citizens. The study period was January 1st 2010 until December 31st 2019. Long-term opioid use was defined as at least two opioid dispensings within two subsequent 90-day periods, with a minimum average use of 10 MME/day for the first 90 days.</p><p><strong>Results: </strong>The study population consisted of 693 495 post-operative opioid users (53.6% women), whereof 73.2% had not used opioids the year before surgery (new users). Among the postoperative opioid users, 3.8% were one-year long-term opioid users. The corresponding figures for new and previous opioid users were 0.4% and 13.1%, respectively. The highest proportions of long-term opioid use were found after transluminal endoscopy, eye surgery and assessments related to surgical procedures. In previous opioid users, the proportion of one-year long-term use was higher among women than men in all age groups, a difference that increased with age.</p><p><strong>Conclusions: </strong>The proportion of postoperative long-term opioid use in Norway is generally low. We detected higher proportions of long-term opioid use after certain types of surgery, but our crude surgery definition warrants further examination. Previous opioid users pose a particular challenge in the management of postoperative pain.</p><p><strong>Trial registration: </strong>The study used national health registry data from the period 2010-2019. A pre-registered analysis plan is available at Open Science Framework.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"25 1","pages":"81"},"PeriodicalIF":2.8,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142494662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}