BMC Pharmacology & Toxicology最新文献

{"title":"Melatonin enhances everolimus efficacy in breast cancer by suppressing mTOR pathway activation and promoting apoptosis and mitochondrial function.","authors":"Şeyma Demirkesen, Yakup İriağaç, Erdoğan Selçuk Şeber, Cenk Aral","doi":"10.1186/s40360-025-00907-1","DOIUrl":"10.1186/s40360-025-00907-1","url":null,"abstract":"<p><strong>Background: </strong>Everolimus is used in the treatment of breast cancer by targeting the PI3K/AKT/mTOR pathway, particularly during anti-hormonal therapy. The efficacy of everolimus is limited due to a feedback loop that supresses mTOR while simultaneously enhancing Akt activation in endocrine-resistant breast cancer. Melatonin (N-acetyl-5-methoxytryptamine) regulates mitochondrial activity, cell death, and autophagy due to its strong free radical scavenging, antioxidant, and anti-inflammatory characteristics. Melatonin, a naturally occurring oncostatic agent, slows tumor growth in a range of malignancies, including breast cancer. Due to its ability to protect healthy cells from oxidative stress and inflammation, along with its anti-cancer properties, melatonin has the potential to serve asan effective adjuvant in breast cancer therapy. It also inhibits the phosphorylation of mTOR and Akt, two essential pathways implicated in breast cancer growth, which may aid in overcoming resistance to targeted treatments like everolimus. The combination effects of melatonin and everolimus on hormone receptor-positive breast cancer remains unexplored. This study examined the effectiveness of melatonin when combined with everolimus for the treatment of hormone receptor-positive breast cancer.</p><p><strong>Methods: </strong>To investigate the effects of melatonin and everolimus combination, we divided MCF-7 cells into four experimental groups: the control, Melatonin (3 mM), Everolimus (30 nM), and a combination of Melatonin and Everolimus (3 mM + 30 nM). Cell viability, apoptosis, autophagy activation, and mitochondrial function were evaluated using established techniques.</p><p><strong>Results: </strong>Based on the cell viability test, the combination of 30 nM everolimus and 3 mM melatonin inhibited phosphorylation of 4E-BP1 and p70S6K, which are downstream effectors of the mTOR pathway, and reduced cell growth. In addition, co-administration of melatonin and everolimus increased apoptosis and led to Sub-G1 phase accumulation. LC3 protein expression and LC3 puncta analysis demonstrated autophagic activity. In terms of mitochondrial function, co-administration of melatonin with everolimus did not cause proton leakage or mitochondrial uncoupling, but did restore everolimus-induced respiratory inhibition.</p><p><strong>Conclusions: </strong>In conclusion, melatonin is thought to improve the effectiveness of everolimus by inhibiting mTOR downstream effectors, enhancing apoptosis, activating autophagy, improving mitochondrial respiration, and reducing MCF-7 growth.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"100"},"PeriodicalIF":2.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970120","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":"The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial.","authors":"Wenqi Huang, Yanneng Kang, Yajun Zhao, Jiao Yang, Changjuan Dai, Weibing Wu, Jinchao Xu, Wen Jin, Xiaolu Wu, Qing Zhou","doi":"10.1186/s40360-025-00937-9","DOIUrl":"10.1186/s40360-025-00937-9","url":null,"abstract":"<p><strong>Background: </strong>Interferons (IFNs) are proteins that combat viruses and regulate the immune system. Studies have demonstrated that aerosol inhalation of IFNα is both effective and safe for treating respiratory infections. However, IFNα has a short half-life and is rapidly cleared by lung defenses. Polyethylene glycol (PEG) ylation is a common strategy to extend the duration of drug action. PegIFNα-2b is a long-acting interferon formed by the covalent binding of 40 kDa Y-shaped branched PEG with recombinant human IFNα-2b. This study aimed to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics of nebulized PegIFNα-2b in healthy adult subjects, providing guidance for further clinical investigations.</p><p><strong>Methods: </strong>This study employed a randomized, controlled clinical trial design with a total of 18 healthy adult subjects enrolled. Participants were randomly assigned in a 1:1:1 ratio to three groups. Treatment group 1 and group 2 received 90 µg and 180 µg of nebulized PegIFNα-2b, respectively, while the control group was administered a combination of 180 µg PegIFNα-2b and 15 mg inhalable Ambroxol Hydrochloride solution, all in a single dose. Safety, tolerability, and blood drug concentration were assessed, along with blood neopterin levels for pharmacokinetic and pharmacodynamic evaluation.</p><p><strong>Results: </strong>The incidence of adverse events (AEs) was 38.9% (7/18) with no significant difference among the groups (P > 0.05). AEs included anemia (N = 5) and leukopenia (N = 2), predominantly of grade 1 severity (6/7), with no severe events. Blood PegIFNα-2b concentrations were below detection limits in most subjects, except one in treatment group 2. Neopterin levels were generally low in treatment group 1 and the control group, with slightly higher observed in most subjects of treatment group 2, but differences were not significant (P > 0.05).</p><p><strong>Conclusions: </strong>Nebulized PegIFNα-2b at doses of 90 µg and 180 µg showed acceptable safety and tolerability. Minimal systemic absorption was observed following inhalation. Further studies are needed to explore its potential, especially in patients with lower respiratory tract infections.</p><p><strong>Clinical trial registration: </strong>ChiCTR2300074909, retrospectively registered in https://www.chictr.org.cn/ at 20 August 2023.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"99"},"PeriodicalIF":2.8,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970016","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":"Comparative study on drug encapsulation and release kinetics in extracellular vesicles loaded with snake venom L - amino acid oxidase.","authors":"Divya Ramesh, Shankar M Bakkannavar, Vinutha R Bhat, K Sreedhara Ranganath Pai, Krishna Sharan","doi":"10.1186/s40360-025-00938-8","DOIUrl":"10.1186/s40360-025-00938-8","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the potential of plasma-derived extracellular vesicles (EVs) as drug delivery carriers by employing two drug-loading techniques: coincubation and freeze-thaw cycles.</p><p><strong>Methods: </strong>EVs isolated via the polyethylene glycol (PEG) precipitation method were characterized via nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The size of the particles was 200.1 ± 66.6 nm. The isolated vesicles were loaded with 1000 µg/ml snake venom L amino acid oxidase (SVLAAO) via the coincubation method and subjected to freeze-thaw cycles to prepare a novel formulation. The encapsulation efficiency (EE) of the loaded EVs was analysed at 30 and 60 min, and in vitro drug release profiles were evaluated for both methods and kinetic model for the same was determined.</p><p><strong>Results: </strong>The coincubation method achieved an EE of 58.08 ± 0.060% after 60 min, which was greater than that of the freeze-thaw method (55.80 ± 0.060%). Drug release studies demonstrated that 93% of the drug was released in 8.5 h by the coincubation method, whereas the freeze-thaw method resulted in faster release (99% in 6.5 h) due to membrane disruption. The best fit value (R²) was highest for zero order kinetics model.</p><p><strong>Conclusion: </strong>In conclusion, the coincubation method preserves EV membrane integrity, enabling sustained drug release, making it a promising strategy for targeted drug delivery applications. This study highlights plasma-derived EVs as innovative carriers for therapeutic delivery.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"98"},"PeriodicalIF":2.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953746","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":"Effect of CYP3A4 inhibitor and induction on the pharmacokinetics and safety of FHND9041, a novel EGFR T790M inhibitor, in healthy Chinese.","authors":"Chang Lu, Dongmei Cheng, Yunqiu Xie, Minghong Shang, Rongzhen Chen, Yongqiang Zhu, Jian Gong, Huan Zhou","doi":"10.1186/s40360-025-00930-2","DOIUrl":"https://doi.org/10.1186/s40360-025-00930-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Non-small cell carcinoma is the main pathologic type of lung cancer, and a large number of clinical trials have shown that epidermal growth factor receptor tyrosinase inhibitors exhibit superior clinical efficacy and lower toxicity compared with chemotherapy. FHND9041 is a new irreversible EGFR T790M mutation-selective small molecule kinase inhibitor, a third-generation EGFR inhibitor developed by Nanjing Chuangte Pharmaceutical Technology Co., Ltd. The aim of this study was to evaluate the effects of oral Itraconazole capsules and oral Rifampicin capsules on the pharmacokinetic profile and safety and tolerability of a single oral dose of FHND9041 capsules in healthy Chinese male subjects.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patients and methods: &lt;/strong&gt;This study employed a single-center, open-label, fixed-sequence design, comprising two parallel groups: Group 1 received FHND9041 40 mg in combination with Itraconazole, while Group 2 received Rifampicin in combination with FHND9041 80 mg. Each group enrolled 16 subjects for a two-period study, with the first period involving monotherapy and the second period involving co-administration. All subjects participating in this clinical trial were healthy adult Chinese males.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In healthy subjects, after a single oral administration of 40 mg FHND9041 capsules, the corrected geometric mean ratios (90% confidence intervals) of FHND9041 C&lt;sub&gt;max&lt;/sub&gt;, AUC&lt;sub&gt;0 - last&lt;/sub&gt;, and AUC&lt;sub&gt;0 - inf&lt;/sub&gt; when co-administered with itraconazole capsules compared to the monotherapy phase were 111.46% (103.26 - 120.30%), 169.53% (156.21 - 183.99%), and 168.25% (156.26 - 181.15%), respectively. The 90% confidence interval for C&lt;sub&gt;max&lt;/sub&gt; fell within the 80-125% range, while the 90% confidence intervals for both AUC&lt;sub&gt;0 - last&lt;/sub&gt; and AUC&lt;sub&gt;0 - inf&lt;/sub&gt; exceeded the 80-125% range. Following a single oral dose of 80 mg FHND9041 capsules, the adjusted geometric mean ratios (90% confidence intervals) of C&lt;sub&gt;max&lt;/sub&gt;, AUC&lt;sub&gt;0 - last&lt;/sub&gt;, and AUC&lt;sub&gt;0 - inf&lt;/sub&gt; for FHND9041 during co-administration with Rifampicin compared to monotherapy were 52.12% (41.95 - 64.74%), 16.47% (13.34 - 20.31%), and 16.51% (13.56 - 20.09%), respectively. The 90% confidence intervals for C&lt;sub&gt;max&lt;/sub&gt;, AUC&lt;sub&gt;0 - last&lt;/sub&gt;, and AUC&lt;sub&gt;0 - inf&lt;/sub&gt; all fell outside the 80 - 125% range. No serious adverse events occurred during the trial.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Co-administration with Rifampicin significantly reduced the exposure of FHND9041. Therefore, it is recommended to avoid co-administration of FHND9041 with Rifampicin and other potent CYP3A4 inducers. Conversely, co-administration with Itraconazole significantly increased the total exposure of FHND9041. Caution is advised when FHND9041 is co-administered with Itraconazole or other strong CYP3A4 inhibitors. Close monitoring of tolerability during co-administration is essential, and dose reduction may be nec","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"97"},"PeriodicalIF":2.8,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12060349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970119","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":"Adverse drug events observed with intrathecal magnesium sulfate as an adjuvant to bupivacaine for spinal anesthesia in patients undergoing elective cesarean section: a meta-analysis.","authors":"Yuanhui Zhang, Yan Huang, Jun Li","doi":"10.1186/s40360-025-00933-z","DOIUrl":"10.1186/s40360-025-00933-z","url":null,"abstract":"<p><strong>Introduction: </strong>Today, the number of cesarean section has drastically increased. Newer scientific reports have shown Magnesium sulfate (MgSO4) to have favorable outcomes for anesthesia. In this analysis, we aimed to systematically compare the adverse drug events observed with intrathecal MgSO4 as an adjuvant to bupivacaine for spinal anesthesia in patients undergoing elective cesarean section.</p><p><strong>Methods: </strong>MEDLINE, EMBASE, Web of Science, Google scholar, http://www.</p><p><strong>Clinicaltrials: </strong>gov , and the Cochrane database were searched for relevant publications comparing the adverse drug events observed with intrathecal MgSO4 as an adjuvant to bupivacaine for spinal anesthesia in patients undergoing elective cesarean section. The RevMan software version 5.4 was used to analyze data in this analysis. Risk ratios (RR) with 95% confidence intervals (CIs) were used to represent analysis for the dichotomous data whereas weighted mean difference (WMD) with 95% CI was used to represent results using continuous data. Heterogeneity was assessed by the Q statistic and the I2 statistic tests.</p><p><strong>Results: </strong>Eleven studies with a total number of 895 participants were included in this analysis whereby 466 patients were assigned to intrathecal MgSO4 and 429 participants were assigned to a control group. The main results of this analysis show that intrathecal MgSO4 as an adjuvant to bupivacaine was associated with a significantly lower risk of shivering (RR: 0.63, 95% CI: 0.48 - 0.83; P = 0.001). In addition, the risks for hypotension (RR: 1.11, 95% CI: 0.86 - 1.44; P = 0.40), nausea and vomiting (RR: 1.08, 95% CI: 0.76 - 1.54; P = 0.65), pruritus (RR: 0.77, 95% CI: 0.51 - 1.17; P = 0.22), and bradycardia (RR: 4.45, 95% CI: 0.97 - 20.36; P = 0.05) were not significantly increased. The sensory (WMD: 23.15, 95% CI: 7.83 - 38.48; P = 0.003), and motor block duration (WMD: 24.29, 95% CI: 16.36 - 32.23; P = 0.00001) and the duration of spinal anesthesia (WMD: 29.24, 95% CI: 13.61 - 44.87; P = 0.0002) were significantly in favor of MgSO4.</p><p><strong>Conclusion: </strong>Intrathecal MgSO4 as an adjuvant to bupivacaine was associated with a significantly lower risk of shivering without causing any increase in other adverse drug events in patients undergoing elective cesarean section. Efficacy outcomes were also appreciated. Larger studies should be able to confirm this hypothesis.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"96"},"PeriodicalIF":2.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961433","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":"Protective effects of Alamandine against doxorubicin-induced liver injury in rats.","authors":"Ava Soltani Hekmat, Maryam Hekmat, Sepehr Ramezanipour, Kazem Javanmardi","doi":"10.1186/s40360-025-00932-0","DOIUrl":"https://doi.org/10.1186/s40360-025-00932-0","url":null,"abstract":"<p><strong>Background: </strong>Doxorubicin (DOX), a common chemotherapeutic agent, is often associated with dose-limiting hepatotoxicity. Alamandine, a peptide of the renin-angiotensin system, has shown antioxidant and anti-inflammatory properties that may counteract these adverse effects.</p><p><strong>Objective: </strong>This study investigated the protective effects of alamandine on DOX-induced liver injury in rats.</p><p><strong>Methods: </strong>Male Wistar rats received DOX (3.75 mg/kg intraperitoneally) on days 14, 21, 28, and 35, reaching a cumulative dose of 15 mg/kg. Alamandine (50 µg/kg/day) was administered continuously via mini-osmotic pumps for 42 days. Liver toxicity was assessed through biochemical measurements of oxidative stress markers, inflammatory cytokines, and liver enzymes, as well as histological examination.</p><p><strong>Results: </strong>DOX administration significantly increased serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels while reducing superoxide dismutase (SOD) and catalase (CAT) activity. Histological analysis revealed hydropic degeneration and hepatocyte necrosis. Alamandine co-treatment restored SOD and CAT activity, reduced MDA and inflammatory markers, and normalized liver enzyme levels, indicating significant hepatoprotection. Furthermore, treatment with alamandine reduced the expression of pro-inflammatory cytokines IL-6, IL-1, and NF-κB induced by DOX, while p53 expression remained unchanged.</p><p><strong>Conclusion: </strong>Alamandine effectively mitigates DOX-induced hepatotoxicity, demonstrating its therapeutic potential as an adjunctive agent in chemotherapy through its antioxidant and anti-inflammatory mechanisms.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"95"},"PeriodicalIF":2.8,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12048956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967997","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":"Hepatoprotective activity of bio-fabricated carbon quantum dots-decorated zinc oxide against carbon tetrachloride-induced liver injury in male rats.","authors":"Fatma El-Zahraa S Mohamed, Hebat-Allah S Tohamy, Mohamed El-Sakhawy","doi":"10.1186/s40360-025-00924-0","DOIUrl":"https://doi.org/10.1186/s40360-025-00924-0","url":null,"abstract":"<p><strong>Background: </strong>Cirrhosis is considered as a severe liver disease that causes partial liver damage as well as total liver destruction; It remains a significant health concern. Sugar cane juice is a particularly beneficial beverage, and its waste products are crucial for treating numerous illnesses. As compared to traditional treatments, zinc-doped carbon quantum dots (Zn/CQDs) are easy-to-prepare, economically invested, high nutritive value and environmentally safe substance.</p><p><strong>Materials & methods: </strong>This study investigated the hepatoprotective effects of zinc-doped carbon quantum dots (Zn/CQDs) against carbon tetrachloride (CCl₄)-induced liver injury in male Wistar albino rats. Zn/CQDs were synthesized using a microwave-assisted method and characterized using FTIR and XRD techniques. Meanwhile, a liver Cirrhosis model induced by carbon tetrachloride (CCl₄) was utilized to determine the inhibitory effects of sugar cane juice mixed with Zn/CQDs against liver Cirrhosis. Biochemical parameters, including AST, ALT, and uric acid, were measured to assess liver function. Histopathological analysis was performed to examine liver tissue damage.</p><p><strong>Results: </strong>In this study, Zn/CQDs were extended from 1.62 to 5.45 nm. The results demonstrated that Zn/CQDs exhibited significant hepatoprotective effects by reducing liver enzyme levels and mitigating histopathological changes. However, the study also highlighted the need for further optimization of the used vehicle delivery method, such as sugarcane juice, which is showed a marginal impact on liver function. Sugar cane juice with Zn/CQDs decreased aspartate amino transferase levels (AST) and improved the uric acid concentration. It means a protection from the toxins effect by controlling the liver enzyme levels; but also, elevated levels of alanine aminotransferase (ALT) indicate ongoing liver injury. Overall, this study provides future insights into the potential of sugar cane juice with Zn/CQDs as a high nutritive value additive to drinks and food; it is investigated for plants waste as a novel green therapeutic strategy for liver diseases. Further research is necessary to explore the underlying mechanisms of action and to optimize their formulation for clinical applications.</p><p><strong>Conclusion: </strong>Overall, this study provides promising insights into the potential of Zn/CQDs as a novel green therapeutic strategy for liver diseases.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"94"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972403","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-drug interaction among elderly patients in Africa: a systematic review and meta-analysis.","authors":"Tekletsadik Tekleslassie Alemayehu, Gebremariam Wulie Geremew, Addisu Afrassa Tegegne, Gebresilassie Tadesse, Demis Getachew, Habtamu Semagn Ayele, Abebaw Setegn Yazie, Setegn Fentahun, Tesfaye Birhanu Abebe, Tefera Minwagaw, Yilkal Abebaw Wassie","doi":"10.1186/s40360-025-00926-y","DOIUrl":"https://doi.org/10.1186/s40360-025-00926-y","url":null,"abstract":"<p><strong>Background: </strong>Elderly patients are at a heightened risk of drug-drug interactions due to their high prevalence of comorbidities, polypharmacy, and age-related physiological changes that alter drug metabolism and excretion. In Africa, these risks are compounded by unique healthcare challenges, including limited access to diagnostic tools, and high burdens of communicable diseases. The aim of this study is to estimate the prevalence of drug-drug interactions and its associated factors among elderly patients in Africa.</p><p><strong>Methods: </strong>Relevant research articles were identified from databases such as HINARI, Science Direct, Embase, PubMed/MEDLINE, Google Scholar, and Research Gate. Data were extracted via a Microsoft Excel spreadsheet and analyzed via STATA version 11.0. Egger regression tests and funnel plot analysis were used to check for publication bias, and the I² statistic was used to evaluate statistical heterogeneity. Sensitivity and subgroup analyses were also conducted to identify potential causes of heterogeneity.</p><p><strong>Results: </strong>Fifteen articles were analyzed, and a total of 5651 potential drug-drug interactions (pDDIs) were identified in 1952 patients, resulting in an average of 2.89 pDDIs per patient. The overall prevalence of pDDIs among elderly patients was 52.53% (95% confidence interval (CI): 35.40, 69.66). However, the prevalence of pDDIs ranged widely from 2.8 to 90.1%. When the severity of the interactions was considered, the prevalence of pDDIs was 20.59%, 69.4%, 34.32% and 1.59% for major, moderate, minor, and contraindicated DDIs, respectively. Polypharmacy, long hospital stays, hypertension and diabetes mellitus were identified as factors associated with pDDIs among elderly patients in Africa.</p><p><strong>Conclusion: </strong>DDIs are prevalent among elderly patients in Africa and are often associated with polypharmacy, prolonged hospitalizations, and the presence of chronic comorbidities, particularly hypertension and diabetes mellitus. Moderate-severity interactions were the most prevalent DDIs. The study suggests addressing this issue requires targeted interventions, including improved pharmacovigilance, enhanced prescribing practices, and integration of DDI risk assessment into routine clinical care. The study also suggests that the database itself could have modified the DDI prevalence rate. As a result, a single DDI identification database needs to be authorized; otherwise, clinical knowledge should be taken in to account when interpreting the information obtained.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"92"},"PeriodicalIF":2.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12039052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963130","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":"Optimization and preparation of in-situ mucoadhesive gel of azithromycin hydroxypropyl-β-cyclodextrin inclusion complex against upper respiratory tract infections.","authors":"Jitu Halder, Shuvam Mishra, Ivy Saha, Ajit Mishra, Ritu Mahanty, Vineet Kumar Rai, Deepak Pradhan, Rakesh Kumar Sahoo, Salim Manoharadas, Muralidhar Tata, Biswakanth Kar, Goutam Ghosh, Goutam Rath","doi":"10.1186/s40360-025-00936-w","DOIUrl":"https://doi.org/10.1186/s40360-025-00936-w","url":null,"abstract":"<p><strong>Background: </strong>Azithromycin (ATM) has limitations, such as poor oral bioavailability and gastrointestinal (GI) side effects that restrict its widespread application.</p><p><strong>Objective: </strong>To develop a localized hydroxy propyl β-cyclodextrin (HP-βCD) inclusion complex-based in situ pH-responsive mucoadhesive gel of azithromycin (ATM) and evaluate its performance for the treatment of upper respiratory tract infections (URTIs).</p><p><strong>Methods: </strong>According to the phase solubility diagram, the ATM HP-βCD complex was prepared and analyzed by FT-IR, DSC, and SEM. Then, using a quality-by-design approach, pH-responsive in-situ gel was prepared. It was characterized in terms of their gelling capacity, pH, spreadability, swelling index, rheological properties and antimicrobial potential.</p><p><strong>Results: </strong>ATM HP- βCD complex 20-fold increased solubility of ATM, i.e., 49.84 ± 1.39 µg/mL with improved dissolution profile compared to pure ATM. Optimized formulation characterized by its gelation pH (6.7), time (1.59 min), and viscosity (1607.9 Pa.s). The developed gel showed a good spreadability index (322.6 ± 0.5%), swelling index (98.26 ± 1.54% after 10 h) and mucoadhesive strength (589 g/cm²). Also, it exhibits a sustained drug release profile for 12 h(94 ± 1.37%) and a broader zone of Staphylococcus aureus growth inhibition (31 ± 3.54 mm).</p><p><strong>Conclusion: </strong>The developed mucoadhesive in situ gels demonstrated promising in vivo performance, primarily due to their effective antimicrobial activity. In vivo, local retention studies confirmed that the formulations adhered to the throat mucosa and remained in place for up to 24 h after application. The findings presented here suggested that this localized delivery system could serve as a useful strategy for improving the therapeutic effects of ATM against URTIs.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"93"},"PeriodicalIF":2.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12038977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975179","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":"Quercetin-mediated restoration of high-fat diet-induced male reproductive dysfunction through modifying spermatogenesis and unraveling 3β-HSD, 17β-HSD, and StAR pathways.","authors":"Mona H Hafez, Shereen B Gad, Yasser S El-Sayed","doi":"10.1186/s40360-025-00918-y","DOIUrl":"https://doi.org/10.1186/s40360-025-00918-y","url":null,"abstract":"<p><strong>Purpose: </strong>We explored the astounding potential of quercetin (QRT) to counteract the determinantal impacts of a high-fat diet (HFD) on testicular function in rat model. The goal was to understand how QRT, and its mechanisms of action can protect testicular health from HFD.</p><p><strong>Methods: </strong>Rats were divided into four groups receiving a control diet, QRT supplement (100 mg/kg), HFD, or HFD plus QRT for 8 weeks. Afterward, assessments were conducted, and reproductive organs were analyzed for hormone levels, gene expression, and subjected to biochemical, histopathological, and immunohistochemical analyses.</p><p><strong>Results: </strong>The HFD caused substantial declines in testicular weight, accessory sex glands and epididymis. The HFD also negatively impacted sperm characteristics including reduced motility, viability, and count, along with impaired morphology. Additionally, the HFD decreased testosterone levels in the testes and serum, impaired antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, and reduced expression of key steroid metabolism enzymes 17β-hydroxysteroid dehydrogenase (17β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), and steroidogenic acute regulatory protein (StAR) involved in testosterone synthesis. These changes were paired with enhanced testicular lipid peroxidation, nitrite, and the inflammatory marker tumor necrosis factor-alpha (TNF-α), reflecting the damaging еffеcts of the HFD. Examination of testicular tissues verified structural damage and significantly fewer proliferating cell nuclear antigen (PCNA)-positive spermatogenic cells in seminiferous tubules of HFD-fed group, confirming HFD's adverse еffеcts.</p><p><strong>Conclusion: </strong>QRT supplementation was able to curb the harmful impacts of the HFD on testicular spermatogenesis and steroidogenesis through its antioxidant, anti-inflammatory and androgen boosting properties.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"90"},"PeriodicalIF":2.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12016373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963302","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}