Pharmacological Research - Reports最新文献

{"title":"Oxidative imbalance induced by dithiocarbamate fungicide, Mancozeb aborts Nrf2 anti-oxidant signaling pathway protection in Vero cell line","authors":"Shilpa T,&nbsp;Vaishnavi A,&nbsp;Aswati Ravindranathan Nair","doi":"10.1016/j.prerep.2025.100041","DOIUrl":"10.1016/j.prerep.2025.100041","url":null,"abstract":"<div><div>Indiscriminate use of the dithiocarbamate fungicide mancozeb (MZB) presents serious risks to both human health and environment. These risks are exacerbated during xenobiotic detoxification in kidneys, where glomerular filtration and excretion can lead to the accumulatation of degradation products in renal cells, rendering them more susceptible to toxic effects. Present study examined cytotoxicity of MZB (1–14 μM) in Vero cells, a sensitive model for nephrotoxicity assessment, over different time periods (6–48 h) and detected EC₅₀ of 11 μM. MZB cytotoxicity was dose- and time-dependent, as shown by a 29 ± 0.02 % cell viability at 14 μM and an EC₅₀ of 9 ± 1 μM at 48 hours. DNA damage at 11 μM MZB (EC₅₀) was evidenced as increased tail length (89 ± 9 μm), tail moment (62 ± 10 a.u.), and tail DNA content (60 ± 6 %). Cytotoxic effects of MZB were associated with the generation of reactive oxygen species (13 ± 0.1 RFU), upregulation of the pro-apoptotic <em>Bax</em> gene, activation of <em>Caspase</em>-3, and downregulation of the anti-apoptotic <em>Bcl</em>-2 gene. The study identified MZB induced redox imbalance and oxidative stress in Vero cells through the disruption of <em>Nrf</em>2-mediated antioxidant signaling pathways.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100041"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116853","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}

{"title":"S-adenosyl-L-methionine modulates hippocampal DNA methylation, exerting fast and long-lasting anti-stress effects independent of alterations in TrkB-mTOR expression","authors":"Amanda J. Sales,&nbsp;Izaque S. Maciel,&nbsp;Francisco S. Guimarães","doi":"10.1016/j.prerep.2025.100032","DOIUrl":"10.1016/j.prerep.2025.100032","url":null,"abstract":"<div><div>Emerging evidence suggests that targeting DNA methylation, a key epigenetic mechanism, may represent a promising therapeutic approach for the treatment of stress-related disorders, including depression. Preclinical studies indicate that the inhibition of DNA methylation induces rapid and sustained antidepressant-like effects through the increased BDNF-TrkB-mTOR signaling in the prefrontal cortex, a brain region associated to the neurobiology of depression and neuroplasticity. S-adenosyl-l-methionine (SAMe), a methyl donor, has been shown to reverse depressive-like behaviors by modulating DNA methylation. However, the molecular mechanisms underlying the SAMe antidepressant effects are not yet fully understood. Therefore, this study evaluated whether SAMe induces rapid and long-lasting behavioral effects by modulating DNA methylation and mTOR-TrkB expression in mice. For this purpose, male Swiss mice received intraperitoneal (i.p.) injections of SAMe (25, 50, and 100 mg/kg) or vehicle (10 mL/kg), 30 minutes, 7 days, or 14 days prior to the forced swimming test (FST) or tail suspension test (TST), two predictive tests of antidepressant action. Global DNA methylation and mTOR-TrkB levels were measured in the hippocampus and prefrontal cortex. SAMe (50 mg/kg) induced a rapid and sustained decrease in immobility time in both the FST and TST, and prevented the stress-induced effects in hippocampal DNA methylation without changing the analyzed protein expression. These findings suggest that the rapid and sustained anti-stress effects observed in mice, resulting from the modulation of hippocampal DNA methylation due to acute SAMe treatment, are not related with TrkB-mTOR signaling.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100032"},"PeriodicalIF":0.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152930","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}

{"title":"Spinal Muscular Atrophy (SMA): Treatment strategies, challenges and future prospects","authors":"Nikunja Kishor Mishra,&nbsp;Amiyakanta Mishra","doi":"10.1016/j.prerep.2025.100031","DOIUrl":"10.1016/j.prerep.2025.100031","url":null,"abstract":"<div><h3>Introduction</h3><div>Spinal muscular atrophy (SMA) is a pediatric neuromuscular disorder that is distinguished by a defect or mutation in the survival motor neuron1 (SMN1) gene. It is a profoundly impactful childhood motor neuron disorder. In its most severe instances and in the absence of treatment, it tragically results in death within the initial two years of life. The disease is identified by muscle weakness and atrophy, predominating in proximal limb muscles. The most common mutation causing SMA is a homozygous deletion of exon 7 of SMN1. Recent therapeutic breakthroughs provide hope to families and patients by tackling the deficiency in SMN protein using gene therapy or alternative genetic manipulation techniques. It is becoming increasingly clear that none of these therapies alone will provide a cure for SMA. Therefore, the objective of the study is to review the correlation between SMN protein levels in tissues and the pathology of SMA. It also aims to provide a comprehensive review of the three currently licensed therapies for SMA, offering a brief overview of their preclinical and clinical studies that led to marketing authorization, coupled with real-world data analysis. Additionally, the study delves into discussions surrounding combined therapy, supplementary therapeutic approaches, challenges in clinical care, and future prospects for the treatment of SMA.</div></div><div><h3>Materials and methods</h3><div>The data for this study were gathered from a range of scholarly sources, including PubMed, Scopus, Springer and other relevant search engines. These sources were selected to ensure access to the latest and most comprehensive literature on SMA management, reflecting current treatment paradigms and advancements in the field.</div></div><div><h3>Results</h3><div>Both preclinical and clinical investigations of risdiplam, onasemnogene abeparvovec, and nusinersen have elucidated the restoration of functional SMN protein and its distribution in both peripheral tissues and central nervous system (CNS) motor neurons, representing a promising therapeutic benefit for the treatment of SMA.</div></div><div><h3>Discussion</h3><div>Clinical trials and real-world data provide robust support for the efficacy and safety profiles of the available drugs. Three therapies, nusinersen, onasemnogene abeparvovec, and risdiplam, aim to increase SMN levels in patients with SMA. Currently, an improvements in safety, efficacy, and motor function have been observed in combination therapies, such as the TOPAZ study (Nusinersen with Aptiegromab), the RESPOND study (Nusinersen with Onasemnogene abeparvovec) and the SAPPHIRE study (Aptiegromab alongside nusinersen or risdiplam).</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100031"},"PeriodicalIF":0.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, and evaluation of in-silico anti-cancer activity of novel gefitinib analogues against 21 target proteins","authors":"Supriti Khan Ushna ,&nbsp;Ananta Kumar Das","doi":"10.1016/j.prerep.2025.100030","DOIUrl":"10.1016/j.prerep.2025.100030","url":null,"abstract":"<div><div>Over time, evidence suggests that numerous drugs have been discovered, and computer modelling, or the \"In silico method\", to understand how anti-cancer proteins interacted. Gefitinib, a quinazoline, inhibits the EGFR tyrosine kinase by attaching to its ATP-binding site. In order to find out how effective new gefitinib analogues are at targeting cancer, this study used molecular docking and ADMET analysis. In this study, the 21 anti-cancer target proteins were utilized to perform docking by using autodock tools. Twenty new analogues were created using ligand-based design, and frontier molecular orbital analysis revealed that the designed molecules are more reactive and softer. The majority of the designed molecules have higher binding affinities than gefitinib, according to the docking studies. Additionally, the analysis revealed that the compounds C-4, C-5, C-7, C-9, C-11, C-12, and C-14 have superior affinity to more than two targets. Docking experiments of the mutated target proteins with designed molecules demonstrate that many target proteins exhibit binding properties comparable to those of the unmutated proteins. According to the literature review on targets, these molecules may be helpful in the treatment of many cancers, including tumour growth, chronic myelogenous leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, acute lymphoid leukemia, thyroid cancers, and salivary gland cancers. It was shown by the binding affinity, drug similarity score, and other ADMET experiments that the designed molecules will have more significant anti-cancer activity.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100030"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152931","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}

{"title":"Curcumin mitigates dichlorvos-initiated multi-organ dysfunction in rats by attenuating systemic oxidative stress and brain inflammatory mRNA transcripts","authors":"Adio Jamiu Akamo ,&nbsp;Boluwatife Adenike Olagunju ,&nbsp;Ofem Effiom Eteng ,&nbsp;Iyabode Adekemi Kehinde ,&nbsp;Adetutu Omolola Ojelabi ,&nbsp;Mushafau Adewale Akinsanya ,&nbsp;Adedayo Adebisi Adebisi ,&nbsp;Tobi Stephen Adekunbi ,&nbsp;Abiola Fatimoh Adenowo ,&nbsp;Flourence Anifowose ,&nbsp;Olufemi Mulkah Ajagun-Ogunleye ,&nbsp;Jacob Kehinde Akintunde","doi":"10.1016/j.prerep.2025.100029","DOIUrl":"10.1016/j.prerep.2025.100029","url":null,"abstract":"<div><div>Organophosphorus pesticides like dichlorvos (DDVP) are widely used for pest control, however their safety is a growing concern due to potential multi-factorial health risks. While curcumin (CUR) is known for its antioxidant capacity, its influence on DDVP-incited multi-organ dysfunction and brain inflammation remain under-researched. This work assessed the ameliorative competence of CUR in a DDVP-mediated systemic intoxication rat model. Rats (42) were randomly appropriated into seven groups (6 rats/group): Control, DDVP only (20 mg.kg⁻¹day⁻¹), DDVP subjected with either CUR (50 and 100 mg.kg⁻¹day⁻¹) or the reference drug atropine (0.2 mg.kg⁻¹day⁻¹), and CUR only (50 and 10 mg.kg⁻¹day⁻¹) were investigated. Rats were afflicted with DDVP orally for seven days, followed by fourteen days of CUR intervention. We humanely killed the rats and harvested their blood and viscera (liver, kidney, heart, lung, and brain) for bioassays twenty-four hours following the final treatment. CUR significantly (p &lt; 0.05) abrogated DDVP-engendered elevations in H₂O₂, NO, and malondialdehyde contents, as well as GST activity; and reversed DDVP-elicited declines in GSH amounts, activities of SOD, catalase, and glutathione peroxidase in across all tissues. In the brain, CUR markedly (p &lt; 0.05) rescinded DDVP-occasioned upregulation of gene expression biomarkers for fibrosis (TGF-β-1), apoptosis regulator (nuclear factor-kB-p65), and pro-apoptosis (p53 and Bax); and markedly abated DDVP-provoked repression of anti-inflammatory cytokine (interleukin-10)]. Wholly CUR therapy mitigated DDVP-engendered multi-organ impairments in rats via rescinding oxidative stress and brain inflammation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100029"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152929","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}

{"title":"Vitamin D3 supplementation improve sexual behaviors of male wistar rats treated with flunitrazepam","authors":"David Tolulope Oluwole ,&nbsp;Oladipupo Samuel Ebiwonjumi ,&nbsp;Lydia Oluwatoyin Ajayi ,&nbsp;Ayodeji Folorunsho Ajayi","doi":"10.1016/j.prerep.2025.100028","DOIUrl":"10.1016/j.prerep.2025.100028","url":null,"abstract":"<div><div>Sexual function, a major component of male health and lifestyle, has been reported to be impaired by flunitrazepam abuse due to its central tranquilizing actions. Therefore, this study examined the role of vitamin D3 (Vit.D3) supplementation on the sexual behavior of flunitrazepam (Flu)-treated male rats. Thirty male Wistar rats, weighing 180–200 g, were allowed access to receptive female rats on three different occasions and screened for sexual proficiency; twenty male rats were selected and randomly allocated into four groups: Vehicle: receiving 0.5 ml of distilled water with 0.5 ml of olive oil;. Flu: receiving 0.35 mg/kg body weight (BW) of flunitrazepam in 0.5 ml of distilled water with 0.5 ml of olive oil; Vit. D3: receiving 0.1 μg/kg/day of vitamin D3 in 0.5 ml of olive oil with 0.5 ml distilled water; Flu + Vit. D3: receiving 0.35 mg/kg of flunitrazepam in 0.5 ml of distilled water with 0.1 μg/kg/day of Vitamin.D3 in 0.5 ml of olive oil. Treatments were administered orally for 56 days. Vitamin D3 supplementation significantly (p &lt; 0.05) reduced mount and intromission latencies, mount frequency and post-ejaculatory interval while increasing intromission frequencies, copulatory and inter-copulatory efficiencies with extended ejaculation latency in flunitrazepam-treated rats. Additionally, Vit.D3 supplementation significantly (p &lt; 0.05) increased serum concentrations of gonadotropin hormones, testosterone, and estradiol, while reducing prolactin concentration. Vitamin D3 supplementation optimized sexual performance and motivation by reducing mount and intromission latencies, improving sexual performance, and preventing premature ejaculation, thereby enhancing copulatory and inter-copulatory efficiencies. Vitamin D3 possibly optimized sexual performance by inhibiting prolactin sretion, which upregulates circulatory pituitary steroids and testicular androgens.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100028"},"PeriodicalIF":0.0,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152932","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}

{"title":"The role of interleukin-1 beta in inflammation and the potential of immune-targeted therapies","authors":"Syed Ali Wijdan ,&nbsp;Syed Muhammad Nasir Abbas Bokhari ,&nbsp;Jenelle Alvares ,&nbsp;Varisha Latif","doi":"10.1016/j.prerep.2025.100027","DOIUrl":"10.1016/j.prerep.2025.100027","url":null,"abstract":"<div><div>Interleukin-1 beta (IL-1β) has emerged as an important therapeutic target, due to its key role in mediating inflammation and tissue damage in different disorders. This study presents a thorough review of the conditions in which (IL-1β) is playing an important role and a summary of the new and ongoing treatments aimed at suppressing its activity. Furthermore, we explored currently available IL-1β targeted treatments, such as IL-1 inhibitors like Canakinumab and Anakinra, and also explained their work at molecular level in reducing inflammation. IL-1β is targeted in inflammatory illnesses in treatment that are beneficial, but there are drawbacks as well which includes the requirement for customized treatment plans, drug resistance, and unpleasant effects. This study also underlines the recent advancements in IL-1β targeted therapies, shedding light on novel approaches.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100027"},"PeriodicalIF":0.0,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152927","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}

{"title":"Functional analysis of quinovic acid derivatives from Sarcocephalus pobeguinii as inhibitors of hepatitis C virus NS3/4A protease","authors":"Arnaud Fondjo Kouam ,&nbsp;Aristide Mfifen Munvera ,&nbsp;Jordas Casares Tchana Tchamba ,&nbsp;Elisabeth Menkem Zeuko’o ,&nbsp;Armelle Gaelle Kwesseu Fepa ,&nbsp;Brice Fredy Nemg Simo ,&nbsp;Felicité Syntia Douanla Somene ,&nbsp;Armel Jackson Seukep ,&nbsp;Pierre Mkounga ,&nbsp;Jules Clément Nguedia Assob ,&nbsp;Frédéric Nico Njayou ,&nbsp;Paul Fewou Moundipa","doi":"10.1016/j.prerep.2024.100026","DOIUrl":"10.1016/j.prerep.2024.100026","url":null,"abstract":"<div><div>This study assessed compounds from <em>Sarcocephalus pobeguinii</em> as potential inhibitors of HCV-NS3/4 A. Ten compounds isolated from <em>S. pobeguinii</em> were initially screened for their inhibitory activity against HCV-NS3/4 A through the fluorescence resonance energy transfer assay. The 50 % inhibitory concentration (IC₅₀) and the inhibition mechanism of active compounds were determined through concentration-response and enzyme-kinetics studies, respectively. The physical interactions between the enzyme and inhibitors were analyzed by thermal shift assay and surface plasmon resonance, while molecular interactions were predicted using molecular docking. The antiviral activity of the hit compounds was tested in a cell-based assay. Three inhibitors of HCV-NS3/4 A: Quinovic acid, Quinovic acid 3-O-[α-D-quinovopyranoside], and Quinovic acid 3-O-[β-D-quinovopyranoside] with IC₅₀ in the micromolar range were successfully identified. They displayed their inhibitory activity through a non-competitive inhibition mechanism and bound to the HCV-NS3/4 A protease in a real-time manner through 1:1 binding and steady-state affinity models, inducing its instability by lowering its melting temperature. The lead compounds effectively inhibited HCV replication at non-toxic concentrations. These results contribute to the valorization of <em>S. pobeguinii</em> as a potential source of efficient inhibitors to reinforce the current therapeutic arsenal for the treatment of HCV infection.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100026"},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143151992","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}

{"title":"Canagliflozin attenuates haloperidol-induced motor and spatial working memory deficits in mice: Evidence of its role in the treatment of Parkinson’s disease","authors":"Emmanuel Semasa Irokosu ,&nbsp;Farouk Adedeji Oladoja ,&nbsp;Sunday O. Olayemi ,&nbsp;Ismail O. Ishola","doi":"10.1016/j.prerep.2024.100025","DOIUrl":"10.1016/j.prerep.2024.100025","url":null,"abstract":"<div><div>Canagliflozin (CANA), a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, has been widely reported for its neuroprotective activity evidenced by its antioxidant and anti-inflammatory properties in brain tissue injury. Thus, it is a promising therapeutic candidate in the treatment of neurodegenerative diseases. This study examined the protective effect of CANA on haloperidol-induced Parkinsonism in mice. Forty-two male mice were divided randomly into seven groups: group 1 - normal control; vehicle (10 mL/kg, <em>p.o</em>.), group 2 - vehicle (pathological control; 10 mL/kg, per oral), groups 3–5, received CANA (25, 50, and 100 mg/kg, <em>p.o</em>., respectively), and the sixth and seventh groups received trihexyphenidyl (THP, 1 mg/kg, <em>p.o.,</em> standard drug), and CANA 100 mg/kg respectively, for 21 consecutive days. Animals in groups 2–6 were given haloperidol (1 mg/kg, <em>i.p</em>.) daily, one hour after pretreatment for 21 days. Spontaneous motor functions assessed with bar and rotarod test as well as working memory by Y-maze test. Thereafter, blood and discrete brain regions were collected for biochemical assays. CANA (25, 50, and 100 mg/kg) demonstrated significant reduction in cataleptic scores in both acute (22, 58, and 76 %, respectively) and chronic (46, 61, and 69 %, respectively) in bar tests at 120 minutes. CANA improved motor coordination through prolongation of latency to fall in the rotarod test. Similarly, haloperidol-induced working memory impairment was reversed by CANA evidenced in significant increase percent alternation behaviour and counteracted dopamine depletion by 57 and 68 % at 50 and 100 mg/kg, respectively. Furthermore, CANA significantly attenuated haloperidol-induced oxidative stress and TNF-α induction. It is of note that CANA did not induce hypoglycaemia in any of the treatment group. Findings from our study demonstrated the ability of canagliflozin to control muscle spasticity/weakness and working memory impairment in Parkinsonism through attenuation of oxidative stress and neuroinflammation.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100025"},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152926","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}

{"title":"Pretreatment with acetylsalicylic acid alleviates UVB irradiation-induced skin pathology in hairless mice and BOC-2 (an ALX/FPR2 receptor antagonist) reduces its activity","authors":"Renata M. Martinez ,&nbsp;Priscila Saito ,&nbsp;Ingrid C. Pinto ,&nbsp;Camilla C.A. Rodrigues ,&nbsp;Victor Fattori ,&nbsp;Cristina P.B. Melo ,&nbsp;Allan J.C. Bussmann ,&nbsp;Larissa Staurengo-Ferrari ,&nbsp;Tiago H. Zaninelli ,&nbsp;Telma Saraiva-Santos ,&nbsp;Michel F. Otuki ,&nbsp;Daniela A. Cabrini ,&nbsp;Marcela M. Baracat ,&nbsp;Sandra R. Georgetti ,&nbsp;Waldiceu A. Verri Jr. ,&nbsp;Rubia Casagrande","doi":"10.1016/j.prerep.2024.100024","DOIUrl":"10.1016/j.prerep.2024.100024","url":null,"abstract":"<div><div>This work aims to investigate if the biological activity of acetylsalicylic acid (ASA) against UVB irradiation-induced skin inflammatory and oxidative injury in hairless mice would be amenable by treatment with BOC-2, an antagonist of the formyl peptide receptor 2 receptor (ALX/FPR2). Mice were treated with BOC-2 and after 30 minutes, they received ASA or Aspirin-Triggered 15-epi-lipoxin A₄ (AT-LXA_4, an agonist of ALX/FPR2), and after 1 hour, they were exposed to UVB irradiation (dose of 4.14 J/cm²). UVB stimulation induced neutrophil and mast cell recruitment, edema, matrix metalloproteinase-9 (MMP-9) activity, collagen degradation, sunburn cell formation, and cytokine production (TNF-α, IL-1β and IL-6). All these parameters were inhibited by ASA or AT-LXA₄. In addition, ASA and AT-LXA₄ enhanced anti-inflammatory cytokines (IL-10 and TGF-β), and attenuated UVB-induced oxidative damage returning the oxidative status to baseline levels in parameters such as ferric reducing ability, free radical scavenging, reduced glutathione levels, catalase activity, superoxide anion production, Nrf2, Nqo1, and gp91^phox mRNA expression. These therapeutic effects of ASA and AT-LXA₄ were reversed by BOC-2. Our results demonstrate that ALX/FPR2 receptor plays an important role in ASA activity against UVB-induced skin pathologies.</div></div>","PeriodicalId":101015,"journal":{"name":"Pharmacological Research - Reports","volume":"3 ","pages":"Article 100024"},"PeriodicalIF":0.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143152928","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}