Naunyn-schmiedebergs Archives of Pharmacology最新文献

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Laboratory and physiological aspects of substitute metazoan models for in vivo pharmacotoxicological analysis
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-19 DOI: 10.1007/s00210-024-03437-5
Paulo Michel Pinheiro Ferreira, Carla Lorena Silva Ramos, José Ivo Araújo Beserra Filho, Micaely Lorrana Pereira Conceição, Mateus Lima Almeida, Débora Caroline do Nascimento Rodrigues, Jhonatas Cley Santos Porto, João Marcelo de Castro e Sousa, Ana Paula Peron
{"title":"Laboratory and physiological aspects of substitute metazoan models for in vivo pharmacotoxicological analysis","authors":"Paulo Michel Pinheiro Ferreira, Carla Lorena Silva Ramos, José Ivo Araújo Beserra Filho, Micaely Lorrana Pereira Conceição, Mateus Lima Almeida, Débora Caroline do Nascimento Rodrigues, Jhonatas Cley Santos Porto, João Marcelo de Castro e Sousa, Ana Paula Peron","doi":"10.1007/s00210-024-03437-5","DOIUrl":"https://doi.org/10.1007/s00210-024-03437-5","url":null,"abstract":"<p>New methods are essential to characterize the performance of substitute procedures for detecting therapeutic action(s) of a chemical or key signal of toxicological events. Herein, it was discussed the applications and advantages of using arthropods, worms, and fishes in pharmacological and/or toxicology assessments. First of all, the illusion of similarity covers many differences between humans and mice, remarkably about liver injury and metabolism of xenobiotics. Using invertebrates, especially earthworms (<i>Eisenia fetida</i>), brine shrimps (<i>Artemia salina</i>, <i>Daphnia magna</i>), and insects (<i>Drosophila melanogaster</i>) and vertebrates as small fishes (<i>Oryzias latipes</i>, <i>Pimephales promelas</i>, <i>Danio rerio</i>) has countless advantages, including fewer ethical conflicts, short life cycle, high reproduction rate, simpler to handle, and less complex anatomy. They can be used to find contaminants in organic matters and water and are easier genetically engineered with orthologous-mutated genes to explore specific proteins involved in proliferative and hormonal disturbances, chemotherapy multidrug resistance, and carcinogenicity. As multicellular embryos, larvae, and mature organisms, they can be tested in bigger-sized replication platforms with 24-, 96-, or 384-multiwell plates as cheaper and faster ways to select hit compounds from drug-like libraries to predict acute, subacute or chronic toxicity, pharmacokinetics, and efficacy parameters of pharmaceutical, cosmetic, and personal care products. Meanwhile, sublethal exposures are designed to identify changes in reproduction, body weight, DNA damages, oxidation, and immune defense responses in earthworms and zebrafishes, and swimming behaviors in <i>A. salina</i> and <i>D. rerio</i>. Behavioral parameters also give specificities on sublethal effects that would not be detected in zebrafishes by OECD protocols.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective effects of α-Pinene against carbon tetrachloride-induced cardiac injury in Wistar rats: modulation of antioxidant and inflammatory responses
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-19 DOI: 10.1007/s00210-024-03434-8
Abdelrahim Alqudah, Esam Qnais, Omar Gammoh, Yousra Bseiso, Mohammed Wedyan
{"title":"Protective effects of α-Pinene against carbon tetrachloride-induced cardiac injury in Wistar rats: modulation of antioxidant and inflammatory responses","authors":"Abdelrahim Alqudah, Esam Qnais, Omar Gammoh, Yousra Bseiso, Mohammed Wedyan","doi":"10.1007/s00210-024-03434-8","DOIUrl":"https://doi.org/10.1007/s00210-024-03434-8","url":null,"abstract":"<p>The escalating global burden of cardiovascular diseases is a growing concern. Numerous research studies have established that plant-derived polyphenols, including α-pinene—a monocyclic monoterpene found in various plant essential oils—have significant effects on key cardiovascular mechanisms. These effects are mediated through their influence on antioxidant systems, cellular signaling pathways, and gene transcription processes. This study investigated the protective effects of α-pinene against cardiac damage caused by carbon tetrachloride (CCl<sub>4</sub>) in Wistar rats. Rats were divided into four groups: a control group receiving saline, a disease control group-administered CCl<sub>4</sub> (1 mL/kg body weight, intraperitoneally), and two treatment groups receiving α-pinene orally at doses of 50 mg/kg and 100 mg/kg body weight alongside CCl<sub>4</sub>, to assess its dose-dependent effects. We conducted comprehensive evaluations, including assessments of serum and cardiac toxicity biomarkers, inflammatory mediators, antioxidant defense mechanisms, lipid peroxidation levels, lipid profiles, and histopathological analyses. CCl<sub>4</sub> exposure resulted in notable increases in free fatty acids (FFA), total cholesterol (TC), triglycerides (TG), phospholipids (PL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) levels, and a decrease in high-density lipoprotein (HDL) levels. Treatment with α-pinene at 100 mg/kg effectively counteracted these lipid profile changes. CCl<sub>4</sub> also caused lipid oxidation and a reduction in antioxidant activities, which were restored to normal levels with α-pinene treatment at 100 mg/kg body weight. Moreover, an upsurge in inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (Hs-CRP)) and cardiac toxicity biomarkers (creatine kinase (CK), and creatine kinase-myocardial band (CK-MB) and troponin) induced by CCl<sub>4</sub> intoxication was reversed by α-pinene. Histopathological studies further validated these findings. The study concludes that α-pinene, administered at a dosage of 100 mg/kg body weight, effectively alleviates cardiac injury induced by CCl<sub>4</sub>. The data suggest that α-pinene exerts its protective effects through modulation of various signaling pathways involved in CCl<sub>4</sub>-induced cardiac toxicity.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cardioprotective effects of GPER agonist in ovariectomized diabetic rats: reversing ER stress and structural changes
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-19 DOI: 10.1007/s00210-024-03438-4
Mohammad Amin Ghaffari Sirizi, Mansour Esmailidehaj, Seyed-Mahdi Mohamadi-Zarch, Maryam Yadeghari, Hossein Azizian
{"title":"Cardioprotective effects of GPER agonist in ovariectomized diabetic rats: reversing ER stress and structural changes","authors":"Mohammad Amin Ghaffari Sirizi, Mansour Esmailidehaj, Seyed-Mahdi Mohamadi-Zarch, Maryam Yadeghari, Hossein Azizian","doi":"10.1007/s00210-024-03438-4","DOIUrl":"https://doi.org/10.1007/s00210-024-03438-4","url":null,"abstract":"<p>The incidence of diabetic cardiomyopathy (DCM) significantly increases in postmenopausal women, suggesting protective roles of estrogen. Excessive endoplasmic reticulum (ER) stress alters myocardial structure, which plays a crucial role in DCM. The G protein-coupled estrogen receptor (GPER) has been demonstrated to have cardioprotective effects, but it remains unclear whether these effects involve the amelioration of structural changes induced by ER stress. The objective of this study was to determine whether GPER can prevent cardiac structural changes by attenuating ER stress. Female ovariectomized (OVX) rats were divided into three groups: OVX, OVX + T2D, and OVX + T2D + G1. T2D was induced by a high-fat diet, and streptozotocin and G1, a GPER agonist, were administered for 6 weeks. Finally, histological changes of the myocardium were examined and the expression of sarcoplasmic reticulum calcium ATPase (SERCA2α), GRP78 as an ER stress marker, and apoptotic signalings were determined by Western blot. We observed that the induction of T2D resulted in an increased cardiac weight index, left ventricular wall thickness, and myocyte diameter. However, GPER activation reversed these changes. T2D increased cardiac protein levels of GRP78, caspase-12, and Bax, while decreasing levels of SERCA2α and Bcl-2. Nevertheless, GPER activation reduced the expression of GRP78 in OVX + T2D rats. Furthermore, GPER activation significantly reduced cardiac caspase-12 and Bax levels and increased SERCA2α and Bcl-2 expression. In conclusion, our data suggest that GPER activation ameliorates DCM by inhibiting ER stress-induced cardiac structural changes. These findings provide a new potential target for therapeutic intervention and drug discovery specifically tailored for postmenopausal diabetic women.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mechanisms and effects of AdipoRon, an adiponectin receptor agonist, on ovarian granulosa cells—a systematic review
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-18 DOI: 10.1007/s00210-024-03441-9
Lucas Fornari Laurindo, Lívia Fornari Laurindo, Victória Dogani Rodrigues, Eduardo Federighi Baisi Chagas, Jéssica da Silva Camarinha Oliveira, Virgínia Maria Cavallari Strozze Catharin, Sandra Maria Barbalho
{"title":"Mechanisms and effects of AdipoRon, an adiponectin receptor agonist, on ovarian granulosa cells—a systematic review","authors":"Lucas Fornari Laurindo, Lívia Fornari Laurindo, Victória Dogani Rodrigues, Eduardo Federighi Baisi Chagas, Jéssica da Silva Camarinha Oliveira, Virgínia Maria Cavallari Strozze Catharin, Sandra Maria Barbalho","doi":"10.1007/s00210-024-03441-9","DOIUrl":"https://doi.org/10.1007/s00210-024-03441-9","url":null,"abstract":"<p>Granulosa cells, crucial components of ovarian follicles, play a fundamental role in follicle development, hormone production, and overall reproductive health. These cells are integral to steroidogenesis, including the synthesis and secretion of key hormones such as estrogen and progesterone. Dysregulation of granulosa cells can lead to reproductive disorders, including polycystic ovary syndrome and infertility. This systematic review provides a comprehensive evaluation of AdipoRon, a synthetic agonist of adiponectin receptors AdipoR1 and AdipoR2, and its effects on ovarian function, with a particular focus on granulosa cells. Due to the absence of clinical trials, the review centers on preclinical studies to explore AdipoRon’s potential therapeutic benefits and to suggest future research directions. A detailed literature search across databases such as PubMed, Scopus, Web of Science, Embase, and Google Scholar was conducted using terms related to AdipoRon and ovarian function. The review encompasses four preclinical studies involving various models: primary granulosa cells from rats, laying hens’ granulosa cells, human luteinized granulosa cells, and chicken ovary follicles. Findings indicate that AdipoRon enhances glucose absorption in rat granulosa cells by stimulating glucose transporter 1 expression, modulates steroid hormone secretion in laying hens’ granulosa cells, and affects cell proliferation and steroidogenesis in human luteinized granulosa cells. Additionally, AdipoRon, in conjunction with recombinant chicken adiponectin, influences ovarian follicular cell proliferation and steroidogenesis in chicken ovary follicles. This review highlights the need for further investigation into AdipoRon’s long-term effects and its potential applications in reproductive health and therapy.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Melatonin for gastric cancer treatment: where do we stand?
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-17 DOI: 10.1007/s00210-024-03451-7
Mahdi Rafiyan, Elham Tootoonchi, Mahdieh Golpour, Amirhossein Davoodvandi, Russel J. Reiter, Reza Asemi, Mehran Sharifi, Sayyed Mehdi Rasooli Manesh, Zatollah Asemi
{"title":"Melatonin for gastric cancer treatment: where do we stand?","authors":"Mahdi Rafiyan, Elham Tootoonchi, Mahdieh Golpour, Amirhossein Davoodvandi, Russel J. Reiter, Reza Asemi, Mehran Sharifi, Sayyed Mehdi Rasooli Manesh, Zatollah Asemi","doi":"10.1007/s00210-024-03451-7","DOIUrl":"https://doi.org/10.1007/s00210-024-03451-7","url":null,"abstract":"<p>Gastric cancer (GC) is the third leading reason of death in men and the fourth in women. Studies have documented an inhibitory function of melatonin on the proliferation, progression and invasion of GC cells. MicroRNAs (miRNAs) are small, non-coding RNAs that play an important function in regulation of biological processes and gene expression of the cells. Some studies reported that melatonin can suppress the progression of GC by regulating the exosomal miRNAs. Thus, melatonin represents a promising potential therapeutic agent for subjects with GC. Herein, we evaluate the existing data of both in vivo and in vitro studies to clarify the molecular processes involved in the therapeutic effects of melatonin in GC. The data emphasize the critical function of melatonin in several signaling ways by which it may inhibit cancer cell proliferation, decrease chemo-resistance, induce apoptosis as well as limit invasion, angiogenesis, and metastasis. This review provides a resource that identifies some of the mechanisms by which melatonin controls GC enlargement. In light of the findings, melatonin should be considered a novel and testable therapeutic mediator for GC treatment.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of arsenic on male and female reproductive function: a review of the pathophysiology and potential therapeutic strategies
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-17 DOI: 10.1007/s00210-024-03452-6
A. E. Adeogun, O. D. Ogunleye, T. M. Akhigbe, P. A. Oyedokun, C. A. Adegbola, W. A. Saka, O. A. Afolabi, R. E. Akhigbe
{"title":"Impact of arsenic on male and female reproductive function: a review of the pathophysiology and potential therapeutic strategies","authors":"A. E. Adeogun, O. D. Ogunleye, T. M. Akhigbe, P. A. Oyedokun, C. A. Adegbola, W. A. Saka, O. A. Afolabi, R. E. Akhigbe","doi":"10.1007/s00210-024-03452-6","DOIUrl":"https://doi.org/10.1007/s00210-024-03452-6","url":null,"abstract":"<p>Arsenic is a ubiquitous metalloid and heavy metal that contributes to the global decline in human fertility. Humans are constantly exposed to arsenic through biotic and abiotic sources, especially ingestion of arsenic-contaminated food and water. Its exposure is associated with several adverse health challenges, including reproductive toxicity. In spite of its reported adverse effects, arsenic exposure remains a global challenge. Hence, this study provides a comprehensive review of the literature on the impact and mechanism of arsenic on male and female reproductive function. Additionally, a review of the potential therapeutic strategies is presented. Evidence from the literature reveals that arsenic upregulates reactive oxygen species (ROS) generation which mediates arsenic-induced suppression of the hypothalamic-pituitary–gonadal axis and inactivation of 3β-HSD and 17β-HSD activities, leading to reduced gonadal steroidogenesis. Through several oxidative stress-dependent signaling, arsenic induces the apoptosis of the germ cells, thus contributing to the development of infertility. At the moment, there is no specific treatment for arsenic-induced reproductive toxicity. However, increasing data form the scientific literature reveals the benefits of antioxidants in ameliorating arsenic-induced reproductive toxicity. These molecules suppress ROS generation and maintain optimal activities of the hypothalamic-pituitary–gonadal axis, leading to optimal steroidogenesis and gametogenesis as well as improved germ cells. Overall, this study revealed the impact and associated mechanism of arsenic-induced reproductive toxicity. It also provides evidence from the literature demonstrating potential therapeutic measures in managing arsenic-induced reproductive toxicity.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Resveratrol enhances the protective effects of calcium supplements on spinal cord injury–induced osteoporosis by targeting the SIRT1/FOXO3a pathway
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-17 DOI: 10.1007/s00210-024-03412-0
Qiuwen Zhong
{"title":"Resveratrol enhances the protective effects of calcium supplements on spinal cord injury–induced osteoporosis by targeting the SIRT1/FOXO3a pathway","authors":"Qiuwen Zhong","doi":"10.1007/s00210-024-03412-0","DOIUrl":"https://doi.org/10.1007/s00210-024-03412-0","url":null,"abstract":"<p>Spinal cord injury (SCI) often leads to osteoporosis due to factors like immobilization and hormonal imbalances. Calcium supplements are prescribed to help maintain bone health, but their efficacy may be limited. This study investigated whether resveratrol (RSV), a polyphenolic compound, could enhance the protective effects of calcium supplements on SCI-induced osteoporosis via the SIRT1/FOXO3a pathway, which regulates bone metabolism. Surgical cord transection induced SCI at the T9 vertebral level. An SCI mouse model was used with four groups: sham, SCI, SCI + 2% calcium, and SCI + calcium + RSV (20 mg/kg body weight). ‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌‌Biomechanical testing, gene expression, and Western blots were performed. Resveratrol and calcium supplementation synergistically preserved bone mass, microarchitecture, strength, and fracture resistance compared to calcium alone after SCI. This was accompanied by upregulated osteoblast markers, downregulated osteoclast markers, and increased SIRT1/FOXO3a expression and activation. The results suggest resveratrol enhances calcium’s bone-protective effects in SCI-induced osteoporosis by modulating the SIRT1/FOXO3a pathway and osteoblast/osteoclast activities. Combining resveratrol with calcium supplementation may be a promising therapeutic approach for managing SCI-induced osteoporosis.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Curcuminoids as natural modulators of necroptosis: therapeutic implications
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-17 DOI: 10.1007/s00210-024-03455-3
Zahra Foroutan, Arrigo Francesco Giuseppe Cicero, Tannaz Jamialahmadi, Amirhossein Sahebkar
{"title":"Curcuminoids as natural modulators of necroptosis: therapeutic implications","authors":"Zahra Foroutan, Arrigo Francesco Giuseppe Cicero, Tannaz Jamialahmadi, Amirhossein Sahebkar","doi":"10.1007/s00210-024-03455-3","DOIUrl":"https://doi.org/10.1007/s00210-024-03455-3","url":null,"abstract":"<p>Necroptosis is an emerging form of programmed cell death characterized by necrosis, an inflammatory type of cell death. Necroptosis is primarily initiated by specific mediators that interact with receptor proteins, leading to the activation of protein kinases RIPK1 and RIPK3. These kinases transmit death signals and recruit and phosphorylate mixed lineage kinase domain-like protein (MLKL), which ultimately triggers cell death and necroptosis. Curcuminoids, natural compounds derived from turmeric, have been shown to possess various therapeutic benefits, including neuroprotective, anti-metabolic syndrome, anti-inflammatory, and anti-cancer effects. In this concise overview, we aim to explore the relationship between curcuminoids and the molecular mechanisms of the necroptosis pathway based on recent in vivo and in vitro studies. The available literature indicates that curcuminoids, mainly curcumin, can act as inhibitors of necroptosis in tissue damage scenarios while serving as a necroptosis inducer in cancer cells. Curcuminoids significantly influence key indicators of necroptosis, highlighting their potential to enhance disease treatment. Future studies should focus on further investigating this important component of turmeric to advance therapeutic approaches.</p>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-17 DOI: 10.1007/s00210-024-03454-4
Samuel Abiodun Kehinde, Abosede Temitope Olajide, Tolulope Peter Fatokun, Dalia Faroud, Najah R. Hadi, Ahmed M. Elgazzar, Adewale Segun James, Mohamed H. Mazhar Ashour
{"title":"Dysfunctional cardiac energy transduction, mitochondrial oxidative stress, oncogenic and apoptotic signaling in DiNP-induced asthma in murine model","authors":"Samuel Abiodun Kehinde, Abosede Temitope Olajide, Tolulope Peter Fatokun, Dalia Faroud, Najah R. Hadi, Ahmed M. Elgazzar, Adewale Segun James, Mohamed H. Mazhar Ashour","doi":"10.1007/s00210-024-03454-4","DOIUrl":"https://doi.org/10.1007/s00210-024-03454-4","url":null,"abstract":"<p>Diisononyl phthalate (DiNP) has been associated with the development of allergies, asthma, and allergic airway inflammation. Through a complex interplay of signals and feedback mechanisms, the lungs communicate with the heart to ensure maintenance of homeostasis and supporting the body’s metabolic demands. In the current study, we assessed the crosstalk between DiNP-induced asthma and cardiac cellular respiration, oxidative stress, apoptotic potential, and induction of oncogenic factors. Ten male BALB/c mice with a weight range of 20–30 g were divided into two groups, each comprising five mice. Group 1 (control), was administered saline orally for a duration of 30 days. In contrast, group 2 (DiNP group), received 50 mg/kg of DiNP to induce asthma. After the final administration and asthma induction, the mice were euthanized, and their hearts were excised, processed, and subjected to biochemical analyses. The DiNP group had downregulated (<i>P</i> &lt; 0.05) activities of the enzymes of glycolysis, tricyclic acid cycle, and electron transport chain except the hexokinase and succinate dehydrogenase activity which were upregulate relative to control. Also, oxidative distress markers (GSH, CAT, and MDA and SOD) were also perturbed. Biomarkers of inflammation (MPO and NO) were considerably higher (<i>P</i> &lt; 0.05) in the heart of DiNP-induced asthma mice as compared with the control group. Furthermore, DiNP-induced asthma group has an increased cardiac caspase-3, Bax, c-Myc and K-ras, and p53 while the Bcl2 decreased when compared with control. Overall, the findings indicate that DiNP-induced asthma impairs cardiac functions by induction of key cardiac oncogenes, downregulation of cardiac energy, transduction of enzymes, and promotion of oxidative stress and cellular death.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Exploring the interplay of natural products and long non-coding RNAs in colorectal cancer: pathogenesis, diagnosis, and overcoming drug resistance
Naunyn-schmiedebergs Archives of Pharmacology Pub Date : 2024-09-17 DOI: 10.1007/s00210-024-03425-9
Hanan Elimam, Mahmoud Gomaa Eldeib, Esma Z. Kizilaslan, Nora A. A. Alhamshry, Abdelkader E. Ashour, Nourhan Elfar, Maie M. Abdel-Wahab, Mohamed Bakr Zaki, Osama A. Mohammed, Abdullah F. Radwan, Mustafa Ahmed Abdel-Reheim, Rewan Moussa, Ahmed S. Doghish
{"title":"Exploring the interplay of natural products and long non-coding RNAs in colorectal cancer: pathogenesis, diagnosis, and overcoming drug resistance","authors":"Hanan Elimam, Mahmoud Gomaa Eldeib, Esma Z. Kizilaslan, Nora A. A. Alhamshry, Abdelkader E. Ashour, Nourhan Elfar, Maie M. Abdel-Wahab, Mohamed Bakr Zaki, Osama A. Mohammed, Abdullah F. Radwan, Mustafa Ahmed Abdel-Reheim, Rewan Moussa, Ahmed S. Doghish","doi":"10.1007/s00210-024-03425-9","DOIUrl":"https://doi.org/10.1007/s00210-024-03425-9","url":null,"abstract":"<p>Colorectal cancer (CRC) is recognized as one of the most prevalent malignancies, both in terms of incidence and mortality rates. Current research into CRC has shed light on the molecular mechanisms driving its development. Several factors, including lifestyle, environmental influences, genetics, and diet, play significant roles in its pathogenesis. Natural compounds such as curcumin, tanshinone, lycorine, sinomenine, kaempferol, verbascoside, quercetin, berberine, and fisetin have shown great promise in the prevention and treatment of CRC. Research has also highlighted the significance of non-coding RNAs (ncRNAs) as biomarkers and therapeutic targets in CRC. Among these, long non-coding RNAs (lncRNAs) have been found to regulate the transcription of genes involved in cancer. LncRNAs contribute to cancer stem cell (CSC) proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), and chemoresistance. Specific lncRNAs, including GAS5, LNC00337, HOTAIR, TPT1-AS1, cCSC1, BCAR4, TUG1, and Solh2, play crucial roles in these processes. They hold potential as novel biomarkers, detectable in bodily fluids and tissues, and could serve as therapeutic targets due to their involvement in drug resistance and sensitivity. These insights could improve CRC treatment strategies, addressing resistance to chemotherapy and radiotherapy. This review article aims to provide a comprehensive analysis of the current knowledge regarding the effectiveness of natural anti-cancer agents in CRC treatment. Additionally, it offers an in-depth evaluation of lncRNAs in CRC, their role in the disease’s progression, and their potential applications in its management.</p><h3 data-test=\"abstract-sub-heading\">Graphical Abstract</h3>\u0000","PeriodicalId":18862,"journal":{"name":"Naunyn-schmiedebergs Archives of Pharmacology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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