Pharmacological ReportsPub Date : 2024-08-01Epub Date: 2024-06-24DOI: 10.1007/s43440-024-00615-3
Weronika Pogoda, Jakub Koczur, Aneta Stachowicz, Józef Madej, Rafał Olszanecki, Maciej Suski
{"title":"Multi-layered metabolic effects of trehalose on the liver proteome in apoE-knockout mice model of liver steatosis.","authors":"Weronika Pogoda, Jakub Koczur, Aneta Stachowicz, Józef Madej, Rafał Olszanecki, Maciej Suski","doi":"10.1007/s43440-024-00615-3","DOIUrl":"10.1007/s43440-024-00615-3","url":null,"abstract":"<p><strong>Background: </strong>Metabolic dysfunction-associated fatty liver disease has been well documented as a key independent risk factor for the development of atherosclerosis. A growing body of evidence suggests that due to its numerous favorable molecular effects, trehalose may exert beneficial effects in counteracting liver steatosis. In our previous study, we described the antiatherosclerotic and antisteatotic properties of trehalose, which we attributed to the induction of autophagy. Considering the pleiotropic activities of trehalose, our present study aimed to extend our preliminary results with the comprehensive examination of proteome-wide changes in the livers of high-fat-fed apoE-/- mice.</p><p><strong>Methods: </strong>Thus, we applied modern, next-generation proteomic methodology to comprehensively analyze the effects of trehalose on the alterations of liver proteins in apoE-/- mice.</p><p><strong>Results: </strong>Our proteomic analysis showed that the administration of trehalose elicited profound changes in the liver proteome of apoE-/- mice. The collected data allowed the identification and quantitation of 3 681 protein groups of which 129 were significantly regulated in the livers of trehalose-treated apoE-/- mice.</p><p><strong>Conclusions: </strong>The presented results are the first to highlight the effects of disaccharide on the induction of proteins mainly related to the metabolism and elimination of lipids, especially by peroxisomal β-oxidation. Our study provides evidence for the pleiotropic activity of trehalose, extending our initial observations of its potential mechanisms responsible for mitigating of liver steatosis, which paves the way for new pharmacological strategies in fatty liver disease.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"902-909"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443240","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}
Pharmacological ReportsPub Date : 2024-08-01Epub Date: 2024-07-04DOI: 10.1007/s43440-024-00569-6
Ruixue Jia, Dandan Meng, Wei Geng
{"title":"Advances in the anti-tumor mechanisms of saikosaponin D.","authors":"Ruixue Jia, Dandan Meng, Wei Geng","doi":"10.1007/s43440-024-00569-6","DOIUrl":"10.1007/s43440-024-00569-6","url":null,"abstract":"<p><p>Saikosaponin D, a saponin compound, is extracted from Bupleurum and is a principal active component of the plant. It boasts a variety of pharmacologic effects including anti-inflammatory, antioxidant, immunomodulatory, metabolic, and anti-tumor properties, drawing significant attention in anti-tumor research in recent years. Research indicates that saikosaponin D inhibits the proliferation of numerous tumor cells, curbing the progression of cancers such as liver, pancreatic, lung, glioma, ovarian, thyroid, stomach, and breast cancer. Its anti-tumor mechanisms largely involve inhibiting tumor cell proliferation, promoting tumor cell apoptosis, thwarting tumor-cell invasion, and modulating tumor cell autophagy. Moreover, saikosaponin D enhances the sensitivity to anti-tumor drugs and augments body immunity. Given its multi-faceted anti-tumor roles, saikosaponin D offers promising potential in anti-tumor therapy. This paper reviews recent studies on its anti-tumor effects, aiming to furnish new theoretical insights for clinical cancer treatments.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"780-792"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Joanna Sobiak, Matylda Resztak, Weronika Sikora, Jacek Zachwieja, Danuta Ostalska-Nowicka
{"title":"Correction: Liquid chromatography-tandem mass spectrometry method for mycophenolic acid and its glucuronide determination in saliva samples from children with nephrotic syndrome.","authors":"Joanna Sobiak, Matylda Resztak, Weronika Sikora, Jacek Zachwieja, Danuta Ostalska-Nowicka","doi":"10.1007/s43440-024-00617-1","DOIUrl":"10.1007/s43440-024-00617-1","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"910"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141446762","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}
Pharmacological ReportsPub Date : 2024-08-01Epub Date: 2024-06-15DOI: 10.1007/s43440-024-00608-2
Przemysław J Danek, Władysława A Daniel
{"title":"The effect of new atypical antipsychotic drugs on the expression of transcription factors regulating cytochrome P450 enzymes in rat liver.","authors":"Przemysław J Danek, Władysława A Daniel","doi":"10.1007/s43440-024-00608-2","DOIUrl":"10.1007/s43440-024-00608-2","url":null,"abstract":"<p><strong>Background: </strong>Our recent studies showed that prolonged administration of novel atypical antipsychotics affected the expression and activity of cytochrome P450 (CYP), as demonstrated in vitro on human hepatocytes and in vivo on the rat liver. The aim of the present work was to study the effect of repeated treatment with asenapine, iloperidone, and lurasidone on the expression of transcription factors regulating CYP drug-metabolizing enzymes in rat liver.</p><p><strong>Methods: </strong>The hepatic mRNA (qRT-PCR) and protein levels (Western blotting) of aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), constitutive androstane receptor (CAR) and peroxisome proliferator-activated receptor (PPARγ) were measured in male Wistar rats after 2 week-treatment with asenapine, iloperidone or lurasidone.</p><p><strong>Results: </strong>The 2-week treatment with asenapine significantly diminished the AhR and PXR expression (mRNA, protein level), and CAR mRNA level in rat liver. Iloperidone lowered the AhR and CAR expression and PXR protein level. Lurasidone did not affect the expression of AhR and CAR, but increased PXR expression. The antipsychotics did not affect PPARγ.</p><p><strong>Conclusions: </strong>Prolonged treatment with asenapine, iloperidone, or lurasidone affects the expression of transcription factors regulating the CYP drug-metabolizing enzymes. The changes in the expression of AhR, CAR, and PXR mostly correlate with alterations in the expression and activity of respective CYP enzymes found in our previous studies. Since these transcription factors are also engaged in the expression of phase II drug metabolism and drug transporters, changes in their expression may affect the metabolism of endogenous substrates and pharmacokinetics of concomitantly used drugs.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"895-901"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327771","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}
Pharmacological ReportsPub Date : 2024-08-01Epub Date: 2024-07-01DOI: 10.1007/s43440-024-00618-0
Paulina Kleniewska, Rafał Pawliczak
{"title":"Can probiotics be used in the prevention and treatment of bronchial asthma?","authors":"Paulina Kleniewska, Rafał Pawliczak","doi":"10.1007/s43440-024-00618-0","DOIUrl":"10.1007/s43440-024-00618-0","url":null,"abstract":"<p><p>Asthma is a lifelong condition with varying degrees of severity and susceptibility to symptom control. Recent studies have examined the effects of individual genus, species, and strains of probiotic microorganisms on the course of asthma. The present review aims to provide an overview of current knowledge on the use of probiotic microorganisms, mainly bacteria of the genus Lactobacillus and Bifidobacterium, in asthma prevention and treatment. Recent data from clinical trials and mouse models of allergic asthma indicate that probiotics have therapeutic potential in this condition. Animal studies indicate that probiotic microorganisms demonstrate anti-inflammatory activity, attenuate airway hyperresponsiveness (AHR), and reduce airway mucus secretion. A randomized, double-blind, placebo-controlled human trials found that combining multi-strain probiotics with prebiotics yielded promising outcomes in the treatment of clinical manifestations of asthma. It appears that probiotic supplementation is safe and significantly reduces the frequency of asthma exacerbations, as well as improved forced expiratory volume and peak expiratory flow parameters, and greater attenuation of inflammation. Due to the small number of available clinical trials, and the use of a wide range of probiotic microorganisms and assessment methods, it is not possible to draw clear conclusions regarding the use of probiotics as asthma treatments.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"740-753"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477252","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}
Pharmacological ReportsPub Date : 2024-08-01Epub Date: 2024-05-24DOI: 10.1007/s43440-024-00604-6
Francesca Frescura, Tibor Stark, Edoardo Tiziani, Serena Di Martino, Jana Ruda-Kucerova, Filippo Drago, Luca Ferraro, Vincenzo Micale, Sarah Beggiato
{"title":"Prenatal MAM exposure raises kynurenic acid levels in the prefrontal cortex of adult rats.","authors":"Francesca Frescura, Tibor Stark, Edoardo Tiziani, Serena Di Martino, Jana Ruda-Kucerova, Filippo Drago, Luca Ferraro, Vincenzo Micale, Sarah Beggiato","doi":"10.1007/s43440-024-00604-6","DOIUrl":"10.1007/s43440-024-00604-6","url":null,"abstract":"<p><strong>Background: </strong>Elevated brain levels of kynurenic acid (KYNA), a metabolite in the kynurenine pathway, are associated with cognitive dysfunctions, which are nowadays often considered as fundamental characteristics of several psychopathologies; however, the role of KYNA in mental illnesses, such as schizophrenia, is not fully elucidated. This study aimed to assess KYNA levels in the prefrontal cortex (PFC) of rats prenatally treated with methylazoxymethanol (MAM) acetate, i.e., a well-validated neurodevelopmental animal model of schizophrenia. The effects of an early pharmacological modulation of the endogenous cannabinoid system were also evaluated.</p><p><strong>Methods: </strong>Pregnant Sprague-Dawley rats were treated with MAM (22 mg/kg, ip) or its vehicle at gestational day 17. Male offspring were treated with the cannabinoid CB1 receptor antagonist/inverse agonist AM251 (0.5 mg/kg/day, ip) or with the typical antipsychotic haloperidol (0.6 mg/kg/day, ip) from postnatal day (PND) 19 to PND39. The locomotor activity and cognitive performance were assessed in the novel object recognition test and the open field test in adulthood. KYNA levels in the PFC of prenatally MAM-treated rats were also assessed.</p><p><strong>Results: </strong>A significant cognitive impairment was observed in prenatally MAM-treated rats (p < 0.01), which was associated with enhanced PFC KYNA levels (p < 0.05). The peripubertal AM251, but not haloperidol, treatment ameliorated the cognitive deficit (p < 0.05), by normalizing the PFC KYNA content in MAM rats.</p><p><strong>Conclusions: </strong>The present findings suggest that the cognitive deficit observed in MAM rats may be related to enhanced PFC KYNA levels which could be, in turn, mediated by the activation of cannabinoid CB1 receptor. These results further support the modulation of brain KYNA levels as a potential therapeutic strategy to ameliorate the cognitive dysfunctions in schizophrenia.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"887-894"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141093692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmacological ReportsPub Date : 2024-08-01Epub Date: 2024-05-17DOI: 10.1007/s43440-024-00601-9
Magdalena Pilz, Kevin Staats, Ojan Assadian, Reinhard Windhager, Johannes Holinka
{"title":"Tolerability of N-chlorotaurine in comparison with routinely used antiseptics: an in vitro study on chondrocytes.","authors":"Magdalena Pilz, Kevin Staats, Ojan Assadian, Reinhard Windhager, Johannes Holinka","doi":"10.1007/s43440-024-00601-9","DOIUrl":"10.1007/s43440-024-00601-9","url":null,"abstract":"<p><strong>Background: </strong>Currently, povidone-iodine (PVP-I) and hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) are frequently used antiseptics in joint infections, but the cytotoxic effects of these solutions are already reported. N-chlorotaurine (NCT) shows a broad-spectrum bactericidal activity and is well tolerated in various tissues, but its effect on human chondrocytes is unknown. The purpose of this study was to assess the cytotoxic effect of NCT, PVP-I, and H<sub>2</sub>O<sub>2</sub> on human chondrocytes compared to a control group in an in vitro setting to get first indications if NCT might be a promising antiseptic in the treatment of septic joint infections for the future.</p><p><strong>Material and methods: </strong>Chondrocytes extracted from human cartilage were incubated with various concentrations of NCT, PVP-I, and H<sub>2</sub>O<sub>2</sub> for 5 and 30 min respectively. EZ4U cell viability kit was used according to the manufacturer's recommendations determining cell viability. To assess cell viability based on their nuclear morphology, cells were stained with acridine-orange and identified under the fluorescence microscope.</p><p><strong>Results: </strong>EZ4U kit showed after 5 and 30 min of incubation a significant decrease in cell viability at NCT 1%, NCT 0.1%, PVP-I, and H<sub>2</sub>O<sub>2</sub>, but not for NCT 0.001% and NCT 0.01%. Acridine-orange staining likewise presented a significant decrease in vital cells for all tested solutions except NCT 0.001% and NCT 0.01% after 5 and 30 min of incubation.</p><p><strong>Conclusion: </strong>Our results demonstrate that NCT is well tolerated by chondrocytes in vitro at the tested lower NCT concentrations 0.01% and 0.001% in contrast to the higher NCT concentrations 1% and 0.1%, PVP-I (1.1%), and H<sub>2</sub>O<sub>2</sub> (3%), for which a significant decrease in cell viability was detected. Considering that the in vivo tolerability is usually significantly higher, our findings could be an indication that cartilage tissue in vivo would tolerate the already clinically used 1% NCT solution. In combination with the broad-spectrum bactericidal activity, NCT may be a promising antiseptic for the treatment of septic joint infections.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"878-886"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958739","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}
Pharmacological ReportsPub Date : 2024-08-01Epub Date: 2024-05-17DOI: 10.1007/s43440-024-00602-8
Pankaj Kadyan, Lovedeep Singh
{"title":"Unraveling the mechanistic interplay of mediators orchestrating the neuroprotective potential of harmine.","authors":"Pankaj Kadyan, Lovedeep Singh","doi":"10.1007/s43440-024-00602-8","DOIUrl":"10.1007/s43440-024-00602-8","url":null,"abstract":"<p><p>Neurodegenerative diseases (NDDs) encompass a range of conditions characterized by the specific dysfunction and continual decline of neurons, glial cells, and neural networks within the brain and spinal cord. The majority of NDDs exhibit similar underlying causes, including oxidative stress, neuroinflammation, and malfunctioning of mitochondria. Elevated levels of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), alongside decreased expression of brain-derived neurotrophic factor (BDNF) and glutamate transporter subtype 1 (GLT-1), constitute significant factors contributing to the pathogenesis of NDDs. Additionally, the dual-specificity tyrosine phosphorylation-regulated kinase 1 A (DYRK1A) gene has emerged as a significant target for the treatment of NDDs at the preclinical level. It significantly contributes to developmental brain defects, early onset neurodegeneration, neuronal loss, and dementia in Down syndrome. Moreover, an impaired ubiquitin-proteosome system (UPS) also plays a pathological role in NDDs. Malfunctioning of UPS leads to abnormal protein buildup or aggregation of α-synuclein. α-Synuclein is a highly soluble unfolded protein that accumulates in Lewy bodies and Lewy neurites in Parkinson's disease and other synucleinopathies. Recent research highlights the promising potential of natural products in combating NDDs relative to conventional therapies. Alkaloids have emerged as promising candidates in the fight against NDDs. Harmine is a tricyclic β-carboline alkaloid (harmala alkaloid) with one indole nucleus and a six-membered pyrrole ring. It is extracted from Banisteria caapi and Peganum harmala L. and exhibits diverse pharmacological properties, encompassing neuroprotective, antioxidant, anti-inflammatory, antidepressant, etc. Harmine has been reported to mediate its neuroprotective via reducing the level of inflammatory mediators, NADPH oxidase, AChE, BChE and reactive oxygen species (ROS). Whereas, it has been observed to increase the levels of BDNF, GLT-1 and anti-oxidant enzymes, along with protein kinase-A (PKA)-mediated UPS activation. This review aims to discuss the mechanistic interplay of various mediators involved in the neuroprotective effect of harmine.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"665-678"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmacological ReportsPub Date : 2024-08-01Epub Date: 2024-07-16DOI: 10.1007/s43440-024-00611-7
Anna Dołoto, Ewelina Bąk, Gabriela Batóg, Iwona Piątkowska-Chmiel, Mariola Herbet
{"title":"Interactions of antidepressants with concomitant medications-safety of complex therapies in multimorbidities.","authors":"Anna Dołoto, Ewelina Bąk, Gabriela Batóg, Iwona Piątkowska-Chmiel, Mariola Herbet","doi":"10.1007/s43440-024-00611-7","DOIUrl":"10.1007/s43440-024-00611-7","url":null,"abstract":"<p><p>Depression is the fourth most serious disease in the world. Left untreated, it is a cause of suicide attempts, emergence or exacerbation worsening of serious diseases, bodily and mental disorders, as well as increased risk of cardiovascular diseases, stroke, diabetes, and obesity, as well as endocrine and neurological diseases. Frequent coexistence of depression and other diseases requires the simultaneous use of several drugs from different therapeutic groups, which very often interact and intensify comorbidities, sometimes unrelated mechanisms. Sufficient awareness of potential drug interactions is critical in clinical practice, as it allows both to avoid disruption of proper pharmacotherapy and achieve substantive results. Therefore, this review aims to analyze the interactions of antidepressants with other concomitant medications. Against the backdrop of experimental research and a thorough analysis of the up-to-date literature, the authors discuss in detail the mechanisms and effects of action of individual drug interactions and adaptogens, including the latest antidepressants.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"714-739"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The effect of phencyclidine-mediated blockade of NMDA receptors in the early postnatal period on glutathione and sulfur amino acid levels in the rat brain as a potential causative factor of schizophrenia-like behavior in adulthood.","authors":"Elżbieta Lorenc-Koci, Magdalena Górny, Grażyna Chwatko, Kinga Kamińska, Małgorzata Iciek, Zofia Rogóż","doi":"10.1007/s43440-024-00607-3","DOIUrl":"10.1007/s43440-024-00607-3","url":null,"abstract":"<p><strong>Background: </strong>Phencyclidine, an NMDA receptor antagonist, is frequently used to model behavioral and neurochemical changes correlated with schizophrenia in laboratory animals. The present study aimed to examine the effects of repeated administration of phencyclidine during early postnatal development on the contents of glutathione and sulfur-containing amino acids, as well as the activity of antioxidant enzymes in the brain of 12-day-old rats, and schizophrenia-like symptoms in adulthood.</p><p><strong>Methods: </strong>Male Sprague-Dawley pups were administered phencyclidine (10 mg/kg) or saline subcutaneously on the postnatal days p2, p6, p9 and p12. In 12-day-old pups, 4 h after the last dose of phencyclidine, the levels of glutathione, cysteine, methionine, and homocysteine, and the enzymatic activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) were measured in the frontal cortex, hippocampus, and striatum. In 70-72-day-old rats, schizophrenia-like symptoms were assessed using behavioral tests.</p><p><strong>Results: </strong>Biochemical data showed that perinatal phencyclidine treatment significantly reduced glutathione and cysteine levels in all brain structures studied, methionine was diminished in the striatum, and homocysteine in both the frontal cortex and striatum. GR activity was increased in the frontal cortex while SODactivity was decreased in the hippocampus. Behaviorally, perinatal phencyclidine induced long-term deficits in social and cognitive function and a decrease in locomotor activity assessed as the time of walking. Finally, perinatal treatment with phencyclidine resulted in a significant reduction in body weight gain over time.</p><p><strong>Conclusion: </strong>Our research provides further evidence for the usefulness of the phencyclidine-induced neurodevelopmental model of schizophrenia for studying the pathogenesis of schizophrenia.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"863-877"},"PeriodicalIF":3.6,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432479","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}