Biomedicine & Pharmacotherapy最新文献

{"title":"The analgesic and gastroprotective activities of the three fungal extracts and their possible correlation with the inhibition of the P2X7 receptor","authors":"Rômulo José Soares-Bezerra ,&nbsp;Natiele Carla da Silva Ferreira ,&nbsp;Tânia Maria de Almeida Alves ,&nbsp;Carlos Leomar Zani ,&nbsp;Luiz Henrique Rosa ,&nbsp;Andrea Surrage Calheiros ,&nbsp;Cristiane Zanon de Souza ,&nbsp;Julliana Alves Azeredo Miranda ,&nbsp;Kátia Regina Ferreira Lima-Quaresma ,&nbsp;Luiz Anastacio Alves ,&nbsp;Válber da Silva Frutuoso","doi":"10.1016/j.biopha.2024.117657","DOIUrl":"10.1016/j.biopha.2024.117657","url":null,"abstract":"<div><div>P2X7 is a purinergic receptor physiologically activated by extracellular ATP. Its activation induces proinflammatory responses, including cytokine release, reactive oxygen species formation, and cell death. Previous <em>in vivo</em> experimental models demonstrated that P2X7 blockade has anti-inflammatory effects; however, there are no drugs used in clinical therapy that act on the P2X7 receptor. In the context of inflammatory diseases, nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used as the first-line treatment; however, their major side effects include stomach ulcer formation, which increases patient morbidity and mortality. Here, we analyzed for the first time the analgesic and gastroprotective activities of three fungal extracts that showed antagonistic effects on P2X7 <em>in vitro</em>. The Antarctic fungal extracts obtained from <em>Vishniacozyma victoriae</em>, <em>Metschnikowia australis</em>, and <em>Ascomycota</em> sp. were tested via <em>in vivo</em> models of acute pain and ethanol-induced ulceration. These three extracts reduced paw licking by approximately 50 %, which is related to pain behavior, and reduced the number of stomach ulcers 3–7 times compared with the control (70 % ethanol), making them more efficient than the lansoprazole, an NSAID drug, and Brilliant Blue G (BBG), a known P2X7 antagonist, which only halves the number of ulcers. Furthermore, the extracts also protected the gastric mucosa and significantly reduced the levels of liver and renal enzymes compared with those in the ethanol group. Taken together, the fungal extracts presented both analgesic and possibly anti-inflammatory activities and had a protective effect on the gastric epithelium.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117657"},"PeriodicalIF":6.9,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ZenoSWATH DIA proteomics and clustering analysis of the effect of cysteamine at the cellular level in cystinotic fibroblasts","authors":"Ignacio Ortea ,&nbsp;Lorena Rodríguez-Martínez ,&nbsp;Mónica Carrera ,&nbsp;Juan A. Fafián-Labora ,&nbsp;Maria C. Arufe ,&nbsp;Miguel González-Barcia ,&nbsp;Anxo Fernández-Ferreiro ,&nbsp;Jesús Mateos","doi":"10.1016/j.biopha.2024.117650","DOIUrl":"10.1016/j.biopha.2024.117650","url":null,"abstract":"<div><div>Cysteamine, an aminothiol, is the only available treatment for cystinosis, an incurable metabolic recessive disease characterized by detrimental symptoms at the renal, ocular, and muscular levels. Cystinosis is due to mutations in the <em>CTNS</em> gene encoding for the lysosomal symporter cystinosine. Cysteamine treatment only delays the symptoms, presents undesirable side effects and the patients depend on it for life. Thus, it is of paramount importance to find new complementary therapeutic targets for the disease, as well as to understand, at the molecular level, both the beneficial and detrimental effects of cysteamine. Here, we have used ZenoSWATH DIA proteomics and clustering analysis to unravel the differences between cystinotic and non-cystinotic skin fibroblasts, and to study the effect of increasing concentrations of cysteamine. Cystinotic cells present significant differences in proteins related to extracellular matrix structure and detoxification. Only a subset of those proteins is reversed by cysteamine in a dose-dependent manner, partially providing an explanation for its therapeutic benefits. Finally, cysteamine <em>per se</em> alters the levels of a group of lysosomal proteins that are not modulated in basal conditions. Our results will be helpful to understand the benefits, deficiencies, and detrimental effects of the cysteamine treatment.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117650"},"PeriodicalIF":6.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanism through which Tripterygium hypoglaucum (Lévl.) Hutch alleviates psoriasis","authors":"Yumei Sun ,&nbsp;Jihong Wang ,&nbsp;Peiyao Hu ,&nbsp;Yi Tang ,&nbsp;Yanwen Wang ,&nbsp;Jianzhou Ye ,&nbsp;Xuesong Yang ,&nbsp;Junlin Yin","doi":"10.1016/j.biopha.2024.117647","DOIUrl":"10.1016/j.biopha.2024.117647","url":null,"abstract":"<div><div><em>Tripterygium hypoglaucum</em> (Lévl.) Hutch rhizome (THH) is mainly used in the clinical setting for the treatment of autoimmune diseases such as rheumatoid arthritis. In total, four active compounds were isolated from THH methanol extract （THH-MeOH）and identified. The HPLC results showed that the proportions of the active ingredients in THH-MeOH (i.e., celastrol, triptolide, and 3-<em>O</em>-acetyloleanolic acid) were 0.79 ‰, 0.46 ‰, and 0.76 ‰, respectively. THH-MeOH attenuated the M5-induced hyperproliferation of HaCaT cells, decreased the mRNA expression levels of inflammatory cytokines, and inhibited the phosphorylation of I<em>κ</em>B<em>α</em>, NF-<em>κ</em>B p65, MAPK, and STAT3/JAK2. Furthermore, THH-MeOH significantly reduced PASI scores in mice; reduced the level of Ki67 expression in skin tissues; decreased the expression of inflammatory cytokines in the skin lesions and serum; and ameliorated the IMQ-induced imbalance in the ROR<em>γ</em>t<em>/</em>Foxp3 ratio. The extract can attenuate psoriasis-like lesions by inhibiting cellular hyperproliferation, ameliorating inflammatory reactions, and modulating immune responses. Our work provides a theoretical basis to support the use of THH for treating psoriasis.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117647"},"PeriodicalIF":6.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142592397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective mechanism of Prim-O-glucosylcimifugin in the treatment of osteoarthritis: Based on lncRNA XIST regulation of Nav1.7","authors":"Changlong Fu ,&nbsp;Yanming Lin ,&nbsp;Qing Lin ,&nbsp;Shujie Lan ,&nbsp;Yanfeng Huang ,&nbsp;Haishui Tu ,&nbsp;Chao Li ,&nbsp;Shiyu Lu ,&nbsp;Xihai Li ,&nbsp;Weihong Zhong ,&nbsp;Dezun Ma","doi":"10.1016/j.biopha.2024.117597","DOIUrl":"10.1016/j.biopha.2024.117597","url":null,"abstract":"<div><div>LncRNA XIST and Nav1.7 have been identified to be significantly associated with the onset of osteoarthritis. Prim-O-glucosylcimifugin (POG) has antiinflammatory and analgesic effects in treating osteoarthritis (OA). However, its molecular mechanism of action remains unclear. This research investigated whether POG inhibits OA cartilage degeneration by regulating Nav1.7 through lncRNA XIST. We observed the relationship between lncRNA XIST and Nav1.7 through in vivo and in vitro experiments, and utilized lentiviral plasmids for XIST overexpression to further validate the protective effect of POG against OA. <em>In vivo</em> experiments revealed the close association of improving OA cartilage morphological changes by POG with lncRNA XIST and Nav1.7 downregulation and related proteins expression. <em>In vitro</em> experiments demonstrated significantly up-regulated lncRNA XIST and Nav1.7 expression in IL1β-induced chondrocytes, and their levels and related protein expression decreased after POG intervention. FISH indicated that POG attenuated the fluorescence intensity of lncRNA XIST in chondrocytes. RT-PCR and Western blot assays revealed the positive correlation of lncRNA XIST and Nav1.7 expression in chondrocytes. Additionally, flow cytometry results revealed that POG intervention reduced OA chondrocyte apoptosis. Therefore, we conclude that POG can mediate lncRNA XIST to regulate Nav1.7 to delay cartilage degeneration, which is an effective way to treat OA. However, lncRNA XIST is not the only target for regulation, and further discussion is needed.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117597"},"PeriodicalIF":6.9,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142594175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria in skeletal system-related diseases","authors":"Liang Pei ,&nbsp;Zhuo Yao ,&nbsp;Dong Liang ,&nbsp;Keda Yang ,&nbsp;Lin Tao","doi":"10.1016/j.biopha.2024.117505","DOIUrl":"10.1016/j.biopha.2024.117505","url":null,"abstract":"<div><div>Skeletal system-related diseases, such as osteoporosis, arthritis, osteosarcoma and sarcopenia, are becoming major public health concerns. These diseases are characterized by insidious progression, which seriously threatens patients’ health and quality of life. Early diagnosis and prevention in high-risk populations can effectively prevent the deterioration of these patients. Mitochondria are essential organelles for maintaining the physiological activity of the skeletal system. Mitochondrial functions include contributing to the energy supply, modulating the Ca²⁺ concentration, maintaining redox balance and resisting the inflammatory response. They participate in the regulation of cellular behaviors and the responses of osteoblasts, osteoclasts, chondrocytes and myocytes to external stimuli. In this review, we describe the pathogenesis of skeletal system diseases, focusing on mitochondrial function. In addition to osteosarcoma, a characteristic of which is active mitochondrial metabolism, mitochondrial damage occurs during the development of other diseases. Impairment of mitochondria leads to an imbalance in osteogenesis and osteoclastogenesis in osteoporosis, cartilage degeneration and inflammatory infiltration in arthritis, and muscle atrophy and excitation<img>contraction coupling blockade in sarcopenia. Overactive mitochondrial metabolism promotes the proliferation and migration of osteosarcoma cells. The copy number of mitochondrial DNA and mitochondria-derived peptides can be potential biomarkers for the diagnosis of these disorders. High-risk factor detection combined with mitochondrial component detection contributes to the early detection of these diseases. Targeted mitochondrial intervention is an effective method for treating these patients. We analyzed skeletal system-related diseases from the perspective of mitochondria and provided new insights for their diagnosis, prevention and treatment by demonstrating the relationship between mitochondria and the skeletal system.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117505"},"PeriodicalIF":6.9,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142578178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The cell cycle inhibitor p21CIP1 is essential for irinotecan-induced senescence and plays a decisive role in re-sensitization of temozolomide-resistant glioblastoma cells to irinotecan","authors":"Jason Sallbach,&nbsp;Melanie Woods,&nbsp;Birgit Rasenberger,&nbsp;Markus Christmann ,&nbsp;Maja T. Tomicic","doi":"10.1016/j.biopha.2024.117634","DOIUrl":"10.1016/j.biopha.2024.117634","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Standard of care for glioblastomas includes radio-chemotherapy with the monoalkylating compound temozolomide. Temozolomide induces primarily senescence, inefficiently killing glioblastoma cells. Recurrences are inevitable. Although recurrences presumably arise from cells evading/escaping TMZ-induced senescence, becoming resistant, they are often again treated with TMZ. As an alternative treatment, irinotecan could be used. Our aim was to examine to what extent and conditions the topoisomerase I inhibitor irinotecan induces senescence and to analyze the underlying mechanism.</div></div><div><h3>Results</h3><div>Multiple glioblastoma lines with different genetic signatures for p53, p21^CIP1, p16^INK4A, p14^ARF, and PTEN were used. By means of LN229 glioblastoma clones which escaped from temozolomide-induced senescence, thus, being potentially recurrence-forming, we show that this escape is accompanied by increased p21^CIP1 protein levels in temozolomide-unexposed senescence-evading clones and inability of temozolomide to induce p21^CIP1. In contrast, irinotecan was still able to induce p21^CIP1 and could elevate senescence and cell death. In combination with the senolytic drug BV6, irinotecan-induced senescence was significantly reduced. Differential response clusters were also observed in paired samples of newly diagnosed and recurrent patients’ tumors. This can partially explain a significantly prolonged progression-free time until surgery for recurrence in patients additionally treated with irinotecan after temozolomide consolidation and upon the first onset of recurrence.</div></div><div><h3>Conclusions</h3><div>p21^CIP1 is essentially involved in induction and maintenance of irinotecan-induced senescence. Neither p16^INK4A, p14^ARF, nor PTEN contribute to senescence, if p21^CIP1 cannot be induced. Based on the positive results of the irinotecan/BV6 treatment, combatting recurrent glioblastomas by targeting senescence cell antiapoptotic pathways (SCAPs) should be considered.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117634"},"PeriodicalIF":6.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated remyelination and immune modulation by the EBI2 agonist 7α,25-dihydroxycholesterol analogue in the cuprizone model","authors":"Klaudia Konieczna-Wolska ,&nbsp;Fionä Caratis ,&nbsp;Mikołaj Opiełka ,&nbsp;Karol Biernacki ,&nbsp;Krzysztof Urbanowicz ,&nbsp;Joanna Klimaszewska ,&nbsp;Piotr Pobiarzyn ,&nbsp;Oliwier Krajewski ,&nbsp;Sebastian Demkowicz ,&nbsp;Ryszard T. Smoleński ,&nbsp;Bartosz Karaszewski ,&nbsp;Klaus Seuwen ,&nbsp;Aleksandra Rutkowska","doi":"10.1016/j.biopha.2024.117653","DOIUrl":"10.1016/j.biopha.2024.117653","url":null,"abstract":"<div><h3>Summary</h3><div>Research indicates a role for EBI2 receptor in remyelination, demonstrating that its deficiency or antagonism inhibits this process. However, activation of EBI2 with its endogenous ligand, oxysterol 7α,25-dihydroxycholesterol (7α,25OHC), does not enhance remyelination beyond the levels observed in spontaneously remyelinating tissue. We hypothesized that the short half-life of the natural ligand might explain this lack of beneficial effects and tested a synthetic analogue, CF₃-7α,25OHC, in the cuprizone model. The data showed that extending the bioavailability of 7α,25OHC is sufficient to accelerate remyelination <em>in vivo</em>. Moreover, the analogue, in contrast to the endogenous ligand, upregulated brain expression of <em>Ebi2</em> and the synthesis of 15 lipids in the mouse corpus callosum. Mechanistically, the increased concentration of oxysterol likely disrupted its gradient in demyelinated areas of the brain, leading to the dispersion of infiltrating EBI2-expressing immune cells rather than their accumulation in demyelinated regions. Remarkably, the analogue CF₃-7α,25OHC markedly decreased the lymphocyte and monocyte counts mimicking the key mechanism of action of some of the most effective disease-modifying therapies for multiple sclerosis. Furthermore, the <em>Cd4+</em> transcripts in the cerebellum and CD4+ cell number in the corpus callosum were reduced compared to vehicle-treated mice. These findings suggest a mechanism by which EBI2/7α,25OHC signalling modulates the immune response and accelerates remyelination <em>in vivo</em>.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117653"},"PeriodicalIF":6.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brazilian red propolis reduces the adhesion of oral biofilm cells and the Toxoplasma gondii intracellular proliferation","authors":"Nagela Bernadelli Sousa Silva ,&nbsp;Gabriel Guimarães Calefi ,&nbsp;Samuel Cota Teixeira ,&nbsp;Thales Alves de Melo Fernandes ,&nbsp;Matheus Hikaru Tanimoto ,&nbsp;Natasha Marques Cassani ,&nbsp;Ana Carolina Gomes Jardim ,&nbsp;Maria Anita Lemos Vasconcelos Ambrosio ,&nbsp;Rodrigo Cássio Sola Veneziani ,&nbsp;Jairo Kenupp Bastos ,&nbsp;Eloisa Amália Vieira Ferro ,&nbsp;Bellisa de Freitas Barbosa ,&nbsp;Marcelo José Barbosa Silva ,&nbsp;Robinson Sabino-Silva ,&nbsp;Carlos Henrique Gomes Martins","doi":"10.1016/j.biopha.2024.117627","DOIUrl":"10.1016/j.biopha.2024.117627","url":null,"abstract":"<div><div>Infectious diseases remain as a significant cause of thousands of deaths annually worldwide. Therefore, this study aimed to investigate the antimicrobial and antiparasitic activity of the crude hydroalcoholic extract and compounds isolated from Brazilian Red Propolis (BRP) against oral pathogens and <em>Toxoplasma gondii</em>, using <em>in vitro</em>, <em>in vivo</em> and <em>in silico</em> approaches. Antimicrobial and synergistic activities were determined using the broth dilution method and the checkerboard assay, respectively. Antibiofilm activity was evaluated by staining with 2 % crystal violet and counting microorganisms. <em>In vivo</em> infection was carried out in <em>Caenorhabditis elegans</em> AU37 larvae and <em>in silico</em> analysis was performed using molecular docking simulations. The effect on growth modulation of <em>T. gondii</em> was evaluated through a β-galactosidase colorimetric assay. Minimum Inhibitory Concentration values ranged from 3.12 to 400 µg/mL. Biofilm Minimum Inhibitory Concentration (MICB₅₀) values ranged from 6.25 to 375 µg/mL, with a significant reduction in the number of viable cells. Furthermore, Guttiferone E and the crude extract reduced cell aggregation and caused damage to the biofilm cell wall. The highest concentrations of the crude extract and Guttiferone E increased the survival and reduced the risk of death of infected and treated larvae. Guttiferone E and Oblongifolin B inhibited the intracellular proliferation of <em>T. gondii</em> and demonstrated several targets of action against bacteria and <em>T. gondii</em> through <em>in silico</em> analysis. These data demonstrate that BRP has antimicrobial and antiparasitic activity against pathogens of clinical relevance, and can be used in the future as phytomedicines.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117627"},"PeriodicalIF":6.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 ethyl acetate extract from Usnea longissima on chemotherapy-associated multiple organ dysfunction in rats","authors":"Eda Bingul ,&nbsp;Seval Bulut ,&nbsp;Renad Mammadov ,&nbsp;Betul Cicek ,&nbsp;Tugba Erkmen Dogru ,&nbsp;Halis Suleyman ,&nbsp;Ali Sefa Mendil","doi":"10.1016/j.biopha.2024.117636","DOIUrl":"10.1016/j.biopha.2024.117636","url":null,"abstract":"<div><h3>Background</h3><div>The toxic effects of doxorubicin and cisplatin in various organs have been associated with oxidative stress. Studies have shown that Usnea longissima has strong antioxidant effects. This study aimed to investigate the protective effect of ethyl acetate extract from Usnea longissima (ULE), which is known to have strong antioxidant effects, on chemotherapeutic-induced heart, kidney, liver, and ovarian toxicity.</div></div><div><h3>Methods</h3><div>Albino Wistar female rats were divided into five groups (12 rats per group): healthy (HG), doxorubicin (DOX), Cisplatin (CIS), Doxorubicin+ ULE (DULE), Cisplatin+ ULE (CULE). In this experiment, ULE was given 100 mg/kg orally. After 1 hour, 2.5 mg/kg doxorubicin and 2.5 mg/kg cisplatin were administered intraperitoneally. Drug treatments continued once a day for seven days. At the end of seven days, six rats from each group were euthanized and heart, kidney, liver, and ovary tissues were analyzed biochemically. The remaining rats were left in the laboratory with male rats for 45 days for reproduction.</div></div><div><h3>Results</h3><div>ULE inhibited chemotherapeutic-induced increase in malondialdehyde, tumor necrosis factor-alpha, and interleukin 6 and a decrease in total glutathione in liver, kidney, and ovarian tissues. ULE also inhibited the increase of blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase in serum. ULE treatment had no protective effect against doxorubicin and cisplatin cardiac toxicity. On the other hand, ULE also decreased the delay in pregnancy induced by chemotherapy.</div></div><div><h3>Conclusion</h3><div>ULE may be considered an adjuvant therapy in patients receiving chemotherapy to reduce liver, kidney, and ovarian toxicity.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117636"},"PeriodicalIF":6.9,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic citalopram effects on the brain neurochemical profile and perfusion in a rat model of depression detected by the NMR techniques – spectroscopy and perfusion","authors":"Iveta Harastova-Pavlova ,&nbsp;Eva Drazanova ,&nbsp;Lucie Kratka ,&nbsp;Petra Amchova ,&nbsp;Maria Hrickova ,&nbsp;Ondrej Macicek ,&nbsp;Jiri Vitous ,&nbsp;Radovan Jirik ,&nbsp;Jana Ruda-Kucerova","doi":"10.1016/j.biopha.2024.117656","DOIUrl":"10.1016/j.biopha.2024.117656","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is a mental illness with a high worldwide prevalence and suboptimal pharmacological treatment, which necessitates the development of novel, more efficacious MDD medication. Nuclear magnetic resonance (NMR) can non-invasively provide insight into the neurochemical state of the brain using proton magnetic resonance spectroscopy (¹H MRS), and an assessment of regional cerebral blood flow (rCBF) by perfusion imaging. These methods may provide valuable <em>in vivo</em> markers of the pathological processes underlying MDD.</div></div><div><h3>Methods</h3><div>This study examined the effects of the chronic antidepressant medication, citalopram, in a well-validated MDD model induced by bilateral olfactory bulbectomy (OB) in rats. ¹H MRS was utilized to assess key metabolite ratios in the dorsal hippocampus and sensorimotor cortex bilaterally, and arterial spin labelling was employed to estimate rCBF in several additional brain regions.</div></div><div><h3>Results</h3><div>The ¹H MRS data results suggest lower hippocampal Cho/tCr and lower cortical NAA/tCr levels as a characteristic of the OB phenotype. Spectroscopy revealed lower hippocampal Tau/tCr in citalopram-treated rats, indicating a potentially deleterious effect of the drug. However, the significant OB model–citalopram treatment interaction was observed using ¹H MRS in hippocampal mI/tCr, Glx/tCr and Gln/tCr, indicating differential treatment effects in the OB and control groups. The perfusion data revealed higher rCBF in the whole brain, hippocampus and thalamus in the OB rats, while citalopram appeared to normalise it without affecting the control group.</div></div><div><h3>Conclusion</h3><div>Collectively, ¹H MRS and rCBF approaches demonstrated their capacity to capture an OB-induced phenotype and chronic antidepressant treatment effect in multiple brain regions.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"181 ","pages":"Article 117656"},"PeriodicalIF":6.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}