BMC Pharmacology & Toxicology最新文献

{"title":"Determination of the latent geometry of atorvastatin pharmacokinetics by transfer entropy to identify bottlenecks.","authors":"Paola Lecca, Angela Re","doi":"10.1186/s40360-025-00948-6","DOIUrl":"10.1186/s40360-025-00948-6","url":null,"abstract":"<p><strong>Background: </strong>In mathematics, a physical network (e.g. biological network, social network, IT network, communication network) is usually represented by a graph. The determination of the metric space (also referred to as latent geometry) of the graph and the disposition of its nodes on it provide important information on the reaction propensity and consequently on the possible presence of bottlenecks in a system of interacting molecules, such as it happens in pharmacokinetics. To determine the latent geometry and the coordinates of nodes, it is necessary to have the dissimilarity or distance matrix of the network, an input that is not always easy to measure in experiments.</p><p><strong>Results: </strong>The main result of this study is the mathematical and computational procedure for determining the distance/dissimilarity matrix between nodes and for identifying the latent network geometry from experimental time series of node concentrations. Specifically, we show how this matrix can be calculated from the transfer entropy between nodes, which is a measure of the flow of information between nodes and thus indirectly of the reaction propensity between them. We implemented a procedure of spectral graph embedding to embed the distance/dissimilarity matrix in flat and curved metric spaces, and consequently to determine the optimal latent geometry of the network. The distances between nodes in the metric space describing the latent geometry can be analyzed to identify bottlenecks in the reaction system. As a case study for this procedure, we consider the pharmacokinetics of atorvastatin, as described by recent studies and experimental time data.</p><p><strong>Conclusions: </strong>The method of determining distances between nodes from temporal measurements of node concentrations through the calculation of transfer entropy makes it possible to incorporate the information of kinetics (inherent in the time series) in the construction of the distance/dissimilarity matrix, and, consequently, in the determination of the network latent geometry, a characterisation of the network itself that is intimately connected to its dynamics, but which has so far been scarcely investigated and taken into account. The results on the case study of the pharmacokinetics of atorvastatin corroborate the usability and reliability of the method within certain limits of the experimental errors on the data.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 Suppl 1","pages":"123"},"PeriodicalIF":2.8,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12188672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494536","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":"Co-treatment of β-carotene with acetamiprid provides protection against acetamiprid induced hepatic and renal toxicity via modulation of the antioxidant system.","authors":"Eatemad A Awadalla, Yahia A Amin, Rana A Ali, Samia A Gbr, Wafaa Ibraheem Gelany, Amna H M Nour","doi":"10.1186/s40360-025-00953-9","DOIUrl":"10.1186/s40360-025-00953-9","url":null,"abstract":"<p><strong>Background: </strong>Acetamiprid (ACMP), one of the most widely used and effective insecticides globally, can pose potential toxicity to mammals. β-carotene (βC) is a prominent carotenoid precursor to vitamin A and exhibits antioxidant properties. This study evaluated the protective effect of βC as an antioxidant against ACMP toxicity in rats.</p><p><strong>Methods: </strong>A total of 40 male albino rats were divided into four groups: the control group received 1% DMSO; the βC group received 100 mg/kg of β-carotene; the ACMP group received 40 mg/kg of acetamiprid; and the ACMP + βC group received both ACMP and βC. Liver and kidney tissues were used for biochemical analyses (total oxidative stress [TOS] and total antioxidant capacity [TAC]), as well as histopathological, histochemical, and immunohistochemical analyses (MPO immunostaining).</p><p><strong>Results: </strong>The ACMP group, compared to the control and βC groups, showed a significant increase in TOS levels (p < 0.001) in both liver and kidney tissue homogenates, along with a significant decrease in TAC in the same tissues. The ACMP + βC group exhibited significantly lower TOS levels (p < 0.01) and significantly higher TAC levels (p < 0.05) than the ACMP group in the liver and kidney tissue homogenates. Furthermore, histopathological alterations were observed in both organs. Changes such as congestion of central veins and blood sinusoids in the liver were noted. In most cases, hepatocytes exhibited basophilic cytoplasm, vacuolar cytoplasm, and pyknotic nuclei. Renal alterations included atrophy of the renal corpuscle, reduced glomerular cellularity, marked dilation of the urinary space, desquamated epithelial cells in the tubular lumen, inflammatory cell infiltration, and congestion of interstitial blood capillaries. In contrast, the ACMP + βC group showed significant improvements in these histopathological changes. MPO immunostaining revealed a significant increase in the ACMP group compared to the other three groups.</p><p><strong>Conclusion: </strong>Co-treatment with β-carotene and acetamiprid reduced ACMP-induced toxicity by enhancing antioxidant capacity and reducing oxidative stress.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"122"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473987","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":"Naringin mitigated doxorubicin-induced kidney injury by the reduction of oxidative stress and inflammation with a synergistic anticancer effect.","authors":"Nahla S Gad, Sameh M Shabana, Maggie E Amer, Azza I Othman, Mohamed A El-Missiry","doi":"10.1186/s40360-025-00947-7","DOIUrl":"10.1186/s40360-025-00947-7","url":null,"abstract":"<p><strong>Background: </strong>The pathophysiology and severity of kidney impairment due to doxorubicin (DOX) treatment are markedly influenced by oxidative stress and inflammation. Naringin (NG), a natural flavonoid, has anti-inflammatory and antioxidant properties. The nephroprotective effect of NG on DOX-induced kidney toxicity was investigated to increase its utility in clinical settings.</p><p><strong>Methods: </strong>DOX toxicity was induced by a single ip injection (15 mg/kg) and for possible protection NG (100 mg/Kg) was used.</p><p><strong>Results: </strong>Kidney damage and dysfunction were indicated by an elevation in the levels of creatinine, urea, uric acid, and the activity of ALP and LDH in serum, KIM-1, and NAGAL in kidney, and a significant decrease in nephrin and podocin in renal tissue. These disrupted glomerular and tubular function indicators were remarkably ameliorated by oral administration of NG (100 mg/kg) daily for 10 days before DOX treatment and continued for an additional four days post-Dox treatment. The nephroprotective effect of NG was confirmed by the improvement of histopathological and PAS histochemical investigations. The mitigating impact of NG was verified by normalization of the redox balance, evidenced by a significant amelioration of ROS levels, oxidative stress markers (MDA, PC, 8-OHdG), and antioxidants (GSH, GPx, GR), as well as upregulation of Nrf2 expression in kidney. Furthermore, NG significantly prevented the increase in the inflammatory mediators (IL-6, IL-1β, TNF-α, and NF-κB) and upregulated the anti-inflammatory IL-10 in DOX-treated rats. The expression of TGF-β1 and the apoptotic protein caspase-3 in the kidneys significantly decreased as a result of the improvement in redox state in renal tissue. Additionally, NG demonstrated anticancer effects and their combination showed synergistic anticancer impact on larynx and colon cancer cell lines in vitro study.</p><p><strong>Conclusions: </strong>NG demonstrated remarkable protection of kidney against DOX treatment.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"121"},"PeriodicalIF":2.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12186448/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144473988","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":"Nano-encapsulated ferulic acid in sesame protein isolate alleviates acrylamide-induced liver toxicity and genotoxicity in rats via oxidative stress and DNA damage modulation.","authors":"Hend A Essa, Elham Ali, Fatma El Zahraa Abd El Hakam, Engy M Akl","doi":"10.1186/s40360-025-00946-8","DOIUrl":"10.1186/s40360-025-00946-8","url":null,"abstract":"<p><strong>Background: </strong>Acrylamide (ACR) induces hepatotoxicity and genotoxicity through oxidative stress and inflammatory processes.</p><p><strong>Aims: </strong>This study explores the potential of ferulic acid encapsulated in sesame protein isolate (SPI) and its nanoform as a non-toxic, effective therapy for ACR-induced oxidative liver injury in rats.</p><p><strong>Methods: </strong>SPI was prepared from defatted sesame flour. SPI exposed to ultrasonic waves to obtain nano SPI, and then ferulic acid was added to form capsules. Fourier transforms infrared spectra, scaning electron microscope, and polarizing optical microscope were used in investigating functional groups and surface morphology of both encapsulations respectively. Rats were divided into four groups, each consisting of six animals: normal control, ACR-treated (20 mg/kg/day), sesame protein encapsulated ferulic acid-treated, and sesame protein nano-encapsulated ferulic acid-treated groups. Both encapsulated forms were administered daily in the diet alongside ACR for two weeks. Liver function indices, oxidative stress biomarkers, DNA fragmentation, comet assay, and histopathological and immunohistochemical examinations were performed.</p><p><strong>Results: </strong>The encapsulation efficiency of the nano-encapsulated form was higher than that of the other forms. Both encapsulated forms significantly improved liver function, elevated levels of GSH, GPx, SOD, and CAT were observed, along with decreased concentrations of MDA, interleukin-6, and tumor necrosis factor-α. The treatments also provided protection against DNA damage and genotoxicity, alleviated histological damage, and reduced liver toxicity and genotoxicity.</p><p><strong>Conclusion: </strong>Both encapsulated forms, especially the nanoform, significantly mitigated liver toxicity. These findings underscore their potential as effective natural therapies for liver damage caused by ACR, and supporting liver health.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"120"},"PeriodicalIF":2.8,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144293275","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 adding fenofibrate versus curcumin to glimepiride in patients with type 2 diabetes: a randomized controlled trial.","authors":"Eman M Nada, Nashwa M El-Gharbawy, Haidy Abbas, Rehab H Werida","doi":"10.1186/s40360-025-00950-y","DOIUrl":"10.1186/s40360-025-00950-y","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Type 2 diabetes is a recognized risk factor for the development of cardiovascular disease. Fenofibrate and curcumin were found to be effective in improving hyperlipidemia in patients with diabetes. This study aimed to evaluate the effect of adding fenofibrate versus curcumin on weight, glycemic status, lipids profile, high-sensitivity C-reactive protein (hs-CRP), fetuin-A, and sirtuin 1 in patients with type 2 diabetes treated with glimepiride.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Method: &lt;/strong&gt;In a double-blind, randomized control trial, 60 patients with type 2 diabetes mellitus were randomly assigned into three groups: Group I was given placebo; Group II curcumin 1100 mg; Group III fenofibrate 160 mg (each administered orally once daily) to ongoing glimepiride 4 mg therapy administered orally once daily for three months. Inclusion criteria were as follows: patients aged 35-70 years, those with uncontrolled type 2 diabetes, hyperlipidemia, and those treated with glimepiride 4 mg. Exclusion criteria were as follows: other types of diabetes, pregnancy, abnormal liver or kidney function tests, using other anti-diabetes medications, and non-adherence to medications. At baseline and after three months of intervention, anthropometric measurements were measured, and blood samples were collected for biochemical analysis of blood glucose, glycated hemoglobin (HbA1c), lipid profile, hs-CRP, fetuin-A, and sirtuin 1. Paired t-test and one-way ANOVA were used for normally distributed data. However, the Wilcoxon signed-rank and the Kruskal-Wallis tests were used to analyze non-normally distributed data.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Three months after the intervention, when the three groups were compared, no significant differences were found regarding weight, body mass index, fasting blood glucose, two-hour postprandial glucose (2 h-PPG), and HbA1c (p &gt; 0.05). Compared to placebo, significant decreases were observed in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), coronary risk index (CRI), atherogenic index (AI), and hs-CRP and increasing sirtuin 1 in the fenofibrate (p &lt; 0.001) and curcumin (p &lt; 0.05) groups. High-density lipoprotein cholesterol (HDL-C) levels in the fenofibrate group were found to be significantly higher than in the placebo group (p &lt; 0.001). Furthermore, when compared to curcumin, fenofibrate significantly reduced waist circumferences and fetuin-A and increased sirtuin 1 (p &lt; 0.05).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Both fenofibrate and curcumin are effective at decreasing lipid profiles and improving inflammatory markers in patients with type 2 diabetes. Fenofibrate might have a superior effect in reducing waist circumference, decreasing fetuin-A, and increasing sirtuin 1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Trial registration: &lt;/strong&gt;This trial was registered (August 27, 2020) on clinical trial.","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"119"},"PeriodicalIF":2.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246270","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":"Integrated network toxicology, machine learning and molecular docking reveal the mechanism of benzopyrene-induced periodontitis.","authors":"Wen Wenjie, Li Rui, Zhuo Pengpeng, Deng Chao, Zhang Donglin","doi":"10.1186/s40360-025-00961-9","DOIUrl":"10.1186/s40360-025-00961-9","url":null,"abstract":"<p><strong>Background: </strong>Environmental pollutants, particularly from air pollution and tobacco smoke, have emerged as significant risk factors. Benzopyrene (BaP), a Group 1 carcinogen, is ubiquitously present in these pollutants, yet its molecular mechanisms in periodontitis remain largely unexplored.</p><p><strong>Methods: </strong>We investigated these mechanisms through an integrated approach combining network toxicology, machine learning, and molecular docking analyses. Data from SwissTargetPrediction, CTD databases, and GEO datasets were analyzed to identify potential targets. Three machine learning algorithms (Support Vector Machine, Random Forest, and LASSO regression) were applied for core target identification, followed by Molecular docking analyses.</p><p><strong>Results: </strong>We identified 11 potential targets associated with BaP-induced periodontitis, primarily involved in cellular response to lipopolysaccharide, endoplasmic reticulum function, and cytokine activity, particularly in IL-17 and TNF signaling pathways. Machine learning analysis identified three core targets: CXCL12, CYP24A1, and HMGCR. Molecular docking demonstrated strong binding affinities between BaP and these targets (binding energies <-5.0 kcal/mol). A diagnostic nomogram based on these core targets achieved high prediction accuracy (AUC = 0.922).</p><p><strong>Conclusions: </strong>This first comprehensive analysis of BaP-induced periodontitis using an integrated computational approach elucidates potential molecular mechanisms and identifies specific therapeutic targets. The diagnostic nomogram developed offers a promising tool for clinical periodontitis risk assessment, providing new perspectives on understanding the impact of environmental pollutants on periodontal health.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"118"},"PeriodicalIF":2.8,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246271","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":"Correction: 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/s40360-025-00956-6","DOIUrl":"10.1186/s40360-025-00956-6","url":null,"abstract":"","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"117"},"PeriodicalIF":2.8,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12143061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233103","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":"In Silico drug evaluation by molecular docking, ADME studies and DFT calculations of 2-(6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl)-N, N-dipropylacetamide.","authors":"Veysel Tahiroğlu, Kenan Gören, Mehmet Bağlan","doi":"10.1186/s40360-025-00958-4","DOIUrl":"10.1186/s40360-025-00958-4","url":null,"abstract":"<p><p>In this study, the structural, electronic, pharmacokinetic, and biological properties of molecule 2-(6-kloro-2-(4-klorofenil)imidazo[1,2-a]piridin-3-il)-N, N-dipropilasetamid (Alpidem), an imidazopyridine derivative anxiolytic known for its high BZ₁ (benzodiazepine-1) receptor affinity and low adverse effect profile, were comprehensively investigated by density functional theory (DFT) and in-silico methods. The alpidem molecule was optimized using the 6-311G(d, p) basis set with the B3LYP and B3PW91 methods; information on the stability and chemical reactivity of the structure was obtained via the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), molecular electrostatic potential (MEP) maps, natural bonding orbital (NBO) analysis, non-linear optical (NLO) properties, and Mulliken charge distributions. Comparative analysis of two different methods has shown that the results are consistent with each other and provide reliable data. In addition, the drug similarity, bioavailability score, bioactivity values, absorption, distribution, metabolism, and excretion (ADME) profiles of the Alpidem molecule were calculated, and it was determined that the Alpidem molecule has pharmacologically favorable properties. Within the scope of molecular docking analyses, its interactions with two different enzymes (PDB ID: 2Z5X and 4BDT) associated with Alzheimer's disease were evaluated. The binding energy values obtained were - 8.00 kcal/mol (2Z5X) and - 9.60 kcal/mol (4BDT), respectively, and the strong binding affinity, especially with the 4BDT protein, suggests that Alpidem may be a potential inhibitor candidate in Alzheimer's disease. This multi-level theoretical study demonstrates that Alpidem is a drug repurposing molecule not only as an anxiolytic but also in neurodegenerative diseases and provides important data that will shed light on experimental studies. The results of this multi-level theoretical study show that Alpidem is a drug repurposing molecule not only as an anxiolytic but also in neurodegenerative diseases and provides important data that will shed light on experimental studies.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"116"},"PeriodicalIF":2.8,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12135494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224153","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":"Bisacurone ameliorates myocardial ischemia/reperfusion injury in rats: regulation of inflammatory and apoptosis pathways via CHOP/GRP78 proteins.","authors":"Xueyan Liao, Qi Wang, Xiaoming Yang, Yuan Yao, Dezhi Zhu, Jing Feng, Kechun Wang","doi":"10.1186/s40360-025-00949-5","DOIUrl":"10.1186/s40360-025-00949-5","url":null,"abstract":"<p><strong>Background: </strong>Myocardial infarction is caused by persistent ischemia with or without reperfusion. Bisacurone, a terpenoid present in turmeric, possesses cardioprotective properties that alleviate heart hypertrophy and diabetic cardiomyopathy. However, its effect on myocardial ischemia-reperfusion damage (MIRI) has yet to be evaluated. Thus, the present study aimed to evaluate the underlying cardioprotective mechanism of bisacurone against MIRI in experimental rats.</p><p><strong>Materials and methods: </strong>Male Sprague-Dawley rats (200-220 g) were administered either vehicle, diltiazem (10 mg/kg), or bisacurone (25, 50, and 100 µg/kg) for 14 days, followed by induction of MIRI by partial ligation of the left anterior descending artery and subsequent reperfusion injury.</p><p><strong>Results: </strong>Bisacurone (50 and 100 µg/kg) significantly (p < 0.05) attenuated IRI-induced cardiac damage, as evidenced by improvements in electrocardiographic, hemodynamic, and left ventricular function tests. Furthermore, cardiac mitochondrial enzyme levels and HO-1 and Bcl-2 mRNA expression were substantially (p < 0.05) upregulated, whereas cardiac oxido-nitrosative stress, ANP, BNP, cTn-I, TNF-α, IL-1, TGF-β, Bax, and caspase-3 mRNA levels were effectively (p < 0.05) downregulated compared to the IRI control. It markedly (p < 0.05) reduced the number of apoptotic cells in cardiac tissue, as determined by flow cytometric analysis. Western blot analysis revealed that bisacurone therapy reduced IRI-induced myocardial apoptosis, as evidenced by a significant (p < 0.05) decrease in CHOP and GRP78-protein expression. Bisacurone also improved IRI-induced histological and ultrastructural aberrations in cardiac tissue.</p><p><strong>Conclusions: </strong>The findings of this study suggest that bisacurone exerts its cardioprotective effects by inhibiting oxido-nitrosative stress, inflammatory release (TNF-α, IL-1β, and TGF-β), apoptosis (Bax and Caspase-3), and by regulating the expression of CHOP and GRP78.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"115"},"PeriodicalIF":2.8,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12128529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207590","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 role of coenzyme Q10 against trihexyphenidyl-induced pulmonary toxicity in Wistar rats.","authors":"Joseph Gbenga Omole, Lydia Oluwatoyin Ajayi, Itunuoluwa Rachael Ajewole, Teniola Osholonge, Oyedayo Phillips Akano, Ayodeji Folorunsho Ajayi","doi":"10.1186/s40360-025-00955-7","DOIUrl":"10.1186/s40360-025-00955-7","url":null,"abstract":"<p><strong>Background: </strong>Trihexyphenidyl (THP), an anticholinergic drug used to manage Parkinson's disease and dystonia, has been associated with oxidative stress and metabolic disturbances, particularly affecting pulmonary function. Long-term exposure to THP may induce lung toxicity through increased oxidative stress, mitochondrial dysfunction, and apoptosis. Coenzyme Q10 (CoQ10), a lipid-soluble antioxidant and mitochondrial cofactor, has been shown to protect against oxidative damage and apoptosis in various models of toxicity. However, its role in mitigating THP-induced pulmonary toxicity remains unexplored. This study investigated the protective effects of CoQ10 against THP-induced pulmonary toxicity in male Wistar rats.</p><p><strong>Methods: </strong>Thirty-two adult male Wistar rats (180-200 g) were randomly assigned to four groups (n = 8 per group): (i) Control (vehicle-treated), (ii) THP (1.5 mg/kg), (iii) CoQ10 (10 mg/kg), and (iv) THP + CoQ10. Treatments were administered orally once daily for 21 days. Body weight was recorded at baseline and endpoint. At the end of treatment, rats were euthanized, and lungs were excised, weighed, and processed for biochemical and histological analyses. Oxidative stress markers were assessed, including catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA). Metabolic enzymes such as lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) were measured. Angiotensin-converting enzyme (ACE) activity was evaluated to assess vascular function, while caspase-3 levels were determined as an apoptotic marker. Histopathological examination of lung tissues was performed using hematoxylin and eosin staining.</p><p><strong>Results: </strong>THP administration resulted in significant weight loss, increased lung weight, oxidative stress (decreased CAT, GPx, SOD, and GSH; increased MDA), and metabolic alterations (elevated LDH, PDH, lactate, and pyruvate). ACE activity was reduced, and caspase-3 was elevated, indicating apoptosis. CoQ10 co-administration mitigated these effects, restoring antioxidant enzyme activity, metabolic balance, and ACE levels while reducing MDA and caspase-3 expression. Histological analysis confirmed that CoQ10 ameliorated THP-induced pulmonary damage.</p><p><strong>Conclusion: </strong>CoQ10 demonstrated significant protective effects against THP-induced oxidative stress, metabolic disturbances, and apoptosis, likely due to its antioxidant and anti-inflammatory properties. These findings suggest CoQ10 as a potential therapeutic agent for THP-induced pulmonary toxicity, warranting further research.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9023,"journal":{"name":"BMC Pharmacology & Toxicology","volume":"26 1","pages":"114"},"PeriodicalIF":2.8,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191442","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}