Reproductive toxicology最新文献_第3页

Teratogenic effects of voriconazole (anti-fungal drug) on Swiss albino mice 伏立康唑（抗真菌药物）对瑞士白化小鼠的致畸作用。

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-08-05 DOI: 10.1016/j.reprotox.2024.108681

{"title":"Teratogenic effects of voriconazole (anti-fungal drug) on Swiss albino mice","authors":"","doi":"10.1016/j.reprotox.2024.108681","DOIUrl":"10.1016/j.reprotox.2024.108681","url":null,"abstract":"<div><p>Antifungals are a class of drugs that target the treatment of invasive fungal infections. This includes polyenes, triazoles, and echinocadins. Among these, azoles are being extensively used nowadays. Triazoles have become standard for the azoles and have replaced amphotericin B as the first line of defence for fungal infections. With the increased cases of fungal infection, which affect a majority of the population at different stages and situations, one such section of the population is pregnant females. The rate and susceptibility of fungal infections are particularly higher in pregnant females, as the immunity of the mother is highly compromised. Systemic fungal infections like invasive aspergillosis, esophageal candidiasis, and candidemia are being treated with new age triazole antifungals like voriconazole. Prolonged and high concentrations of this drug are associated with various developmental anomalies. With this aim, teratogenic studies were performed on pregnant female mice during gestation and the weaning/lactation period to observe the effects of voriconazole at different dosages (8 mg/kg b.w., 10 mg/kg b.w., and 20 mg/kg b.w.). Pregnant dams were subjected to 20 mg/kg b.w. Voriconazole had a small litter size and a high number of resorptions. Craniofacial defects in the form of reduced ossification and widely open sutures, the presence of the 14th rib, asymmetry in the sternebrae, and the absence of ossified distal phalanges were some of the skeletal anomalies which were significant in the foetus and pups subjected to both 10 mg/kg b.w. and 20 mg/kg b.w. doses of voriconazole.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of levamlodipine benzenesulfonate compound I for embryo-fetal developmental toxicity in SD rats and genotoxicity 评估苯磺酸左旋氨氯地平化合物 I 对 SD 大鼠胚胎-胎儿发育的毒性和遗传毒性。

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-07-31 DOI: 10.1016/j.reprotox.2024.108676

{"title":"Evaluation of levamlodipine benzenesulfonate compound I for embryo-fetal developmental toxicity in SD rats and genotoxicity","authors":"","doi":"10.1016/j.reprotox.2024.108676","DOIUrl":"10.1016/j.reprotox.2024.108676","url":null,"abstract":"<div><p>In the present study, the effects of levamlodipine benzenesulfonate on the development of fertile Sprague-Dawley (SD) rats, their embryos, and littermates were assessed using an embryo-fetal developmental toxicity test. Maternal body weight reduction was observed at a dose of 20 mg/kg, but it recovered after treatment cessation. The 20 mg/kg dose group showed a skewed sex ratio in fetal rats, with a higher proportion of males. While some effects on fetal sternum development were observed at 20 mg/kg, no skeletal malformations were observed. No significant gross morphological abnormalities were detected in the dams (mothers), no significant embryotoxicity or foetotoxicity in fetal rats and no significant effects on fetal length and weight development at doses of 5 and 10 mg/kg. Genotoxicity was evaluated using a combination of the Ames test, the Chinese hamster ovary (CHO) cell chromosome aberration assay, and the ICR mouse bone marrow micronucleus test. The Ames test results indicated substantial bacteriostatic effects at doses of 500 and 5000 mg/dish, with no mutagenicity observed at doses of 0.5, 5, and 50 mg/dish. No significant effect on the aberration rate of CHO cell chromosomes was found at doses of 2.8, 5.6, and 11.2 mg/mL. In the ICR mouse micronucleus test, no micronucleus-inducing effect was observed at doses of 3.125, 6.25, and 12.5 mg/kg in each treatment group. In conclusion, under the conditions of this experiment, the no-observed-adverse-effect level (NOAEL) for developmental toxicity of levamlodipine benzenesulfonate in fertile SD rats, their embryos, and littermates was established to be 10 mg/kg/day. Levamlodipine benzenesulfonate did not exhibit significant genotoxicity.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of Humanin and MOTS-c on ameliorating reproductive damage induced by prepubertal cyclophosphamide chemotherapy in male mice Humanin 和 MOTS-c 对改善雄性小鼠青春期前环磷酰胺化疗引起的生殖损伤的影响

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-07-28 DOI: 10.1016/j.reprotox.2024.108674

{"title":"Effect of Humanin and MOTS-c on ameliorating reproductive damage induced by prepubertal cyclophosphamide chemotherapy in male mice","authors":"","doi":"10.1016/j.reprotox.2024.108674","DOIUrl":"10.1016/j.reprotox.2024.108674","url":null,"abstract":"<div><p>Male patients who undergo prepubertal chemotherapy face the dual problems of fertility preservation in adulthood, including low testosterone, hypersexual function, and infertility. Humanin, as a small polypeptide coded within the mitochondrial DNA, with the mitochondrial short open reading frame named MOTS-c, both was believed to regulate mitochondrial homeostasis, be anti-inflammatory, improve metabolism, anti-apoptosis, and multiple pharmacological effects. However, there exists little evidence that reported Humanin and MOTS-c 's effects on moderating male spermatogenic function of patients after prepubertal chemotherapy. Here, we found that in vivo, mitochondrial polypeptides Humanin analog (HNG) and MOTS-c efficaciously protected the testicular spermatogenic function from reproductive injury. Moreover, transcriptomic sequencing analysis was performed to verify the differentially expressed genes such as Piwil2, AGT (angiotensinogen), and PTGDS (glycoprotein prostaglandin D2 synthase), which are related to the regulation of male reproductive function of male mice induced by prepubertal chemotherapy. Collectively, our data revealed that both Humanin analogs HNG and MOTS-c are the feasible approaches attached to the protective effect on the male reproductive function damaged by prepubertal chemotherapy.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141842261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Air pollution-linked epigenetic modifications in placental DNA: Prognostic potential for identifying future foetal anomalies 空气污染导致的胎盘 DNA 表观遗传学修饰：识别未来胎儿异常的预后潜力。

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-07-27 DOI: 10.1016/j.reprotox.2024.108675

{"title":"Air pollution-linked epigenetic modifications in placental DNA: Prognostic potential for identifying future foetal anomalies","authors":"","doi":"10.1016/j.reprotox.2024.108675","DOIUrl":"10.1016/j.reprotox.2024.108675","url":null,"abstract":"<div><p>Prenatal exposure to air pollution is a significant risk factor for the mother and the developing foetus. The accumulation of pollutants in the placenta can cause a self-cascade loop of pro-inflammatory cytokine responses and DNA double-strand breaks. Previous research has shown that airborne particulate matter can damage the epigenome and disturb mitochondrial machinery, ultimately impairing placental function. Mitochondria are essential for preserving cellular homeostasis, energy metabolism, redox equilibrium, and epigenetic reprogramming. As these organelles are subtle targets of environmental exposures, any disruption in the signaling pathways can result in epigenomic instability, which can impact gene expression and mitochondrial function. This, in turn, can lead to changes in DNA methylation, post-translational histone modifications, and aberrant expression of microRNAs in proliferating trophoblast cells. The placenta has two distinct layers, cytotrophoblasts, and syncytiotrophoblasts, each with its mitochondria, which play important roles in preeclampsia, gestational diabetes, and overall health. Foetal nucleic acids enter maternal circulation during placental development because of necrotic, apoptotic, and inflammatory mechanisms. These nucleic acids reflect normal or abnormal ongoing cellular changes during prenatal foetal development. Detecting cell-free DNA in the bloodstream can be a biomarker for predicting negative pregnancy-related outcomes and recognizing abnormalities in foetal growth. Hence, a thorough understanding of how air pollution induces epigenetic variations within the placenta could offer crucial insights into underlying mechanisms and prolonged repercussions on foetal development and susceptibility in later stages of life.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ethylene oxide suppresses boar sperm function during capacitation 环氧乙烷抑制公猪精子在获能过程中的功能

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-07-26 DOI: 10.1016/j.reprotox.2024.108678

{"title":"Ethylene oxide suppresses boar sperm function during capacitation","authors":"","doi":"10.1016/j.reprotox.2024.108678","DOIUrl":"10.1016/j.reprotox.2024.108678","url":null,"abstract":"<div><p>Ethylene oxide (E.O) is an epoxide compound, and it has been utilized as a sterilizer or production of ether compounds in several industries. Although the toxic effects of E.O on bacteria and mammals have been reported, its effects on male reproductive toxicity during sperm capacitation are not fully understood. Therefore, this study was designed to evaluate the effects of E.O exposure during sperm capacitation. Boar spermatozoa were treated with various E.O concentrations (0, 0.1, 1, 10, and 100 μМ). After exposure, sperm motility, motion kinematics, capacitation status, intracellular ATP levels, cell viability, expression levels of protein kinase A (PKA) activation, and tyrosine phosphorylation were evaluated. Results revealed that E.O exposure significantly decreased sperm motility, motion kinematics, and intracellular ATP levels but significantly increased the capacitated spermatozoa. In addition, the PKA activation and tyrosine phosphorylation were abnormally changed. According to our results, E.O may cause toxic effects on sperm function during capacitation, which induces male reproductive toxicity. Consequently, we suggest that male reproductive toxicity should be considered when using E.O.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ameliorative effects of sinapic acid against vancomycin-induced testicular oxidative damage, apoptosis, inflammation, testicular histopathologic disorders and decreased epididymal sperm quality 山奈酸对万古霉素引起的睾丸氧化损伤、细胞凋亡、炎症、睾丸组织病理学紊乱和附睾精子质量下降有改善作用。

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-07-25 DOI: 10.1016/j.reprotox.2024.108666

{"title":"Ameliorative effects of sinapic acid against vancomycin-induced testicular oxidative damage, apoptosis, inflammation, testicular histopathologic disorders and decreased epididymal sperm quality","authors":"","doi":"10.1016/j.reprotox.2024.108666","DOIUrl":"10.1016/j.reprotox.2024.108666","url":null,"abstract":"<div><p>In this study, it was aimed to determine the effect of sinapic acid (SNP), a polyphenol with antioxidant, anti-inflammatory and antibacterial properties, on testicular damage caused by vancomycin (VCM), a widely used antibiotic against gram positive bacteria. A total of 35 male Sprague Dawley rats were used in the study, divided into five groups: control, VCM, SNP, VCM + SNP 10, and VCM + SNP 20. Following a week of oral administration, the rats were euthanized under sevoflurane anesthesia. While the VCM group had a significant increase in MDA levels, the SNP administration inhibited the increase in MDA levels. VCM led to a significant decrease in GSH levels, SOD, CAT, and GPx activity in the testicular tissue of rats, while SNP administration increased these antioxidant levels. SNP administration decreased the mRNA expression levels of VCM induced Nrf-2, HO-1, and NQO1 in testicular tissue while increasing the levels of MAPK14, MAPK15, JNK, P53, Apaf-1, Caspase-3, Caspase-6, Caspase-9, and Beclin-1 mRNA transcript levels. The VCM group showed a significant increase in Bax and NF-κB levels in testicular tissue, while Bcl-2 levels decreased. VCM significantly decreased sperm motility and increased the percentage of damaged sperm in rats. Histopathological results revealed that VCM caused disruption of basement membranes and disorganization of seminiferous tubules, but SNP administration preserved testicular histology. As a result, VCM increased oxidative stress, apoptosis, and autophagy in the testicular tissue of rats, altered testicular histopathology, and decreased sperm quality, while SNP decreased these effects.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","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 Bisphenol A exposure on maternal gut microbial homeostasis, placental function, and fetal development during pregnancy 孕期接触双酚 A 对母体肠道微生物稳态、胎盘功能和胎儿发育的影响

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-07-25 DOI: 10.1016/j.reprotox.2024.108677

{"title":"Impact of Bisphenol A exposure on maternal gut microbial homeostasis, placental function, and fetal development during pregnancy","authors":"","doi":"10.1016/j.reprotox.2024.108677","DOIUrl":"10.1016/j.reprotox.2024.108677","url":null,"abstract":"<div><p>Pregnancy is extremely vulnerable to external environmental influences. Bisphenol A, an endocrine-disrupting chemical, poses a significant environmental hazard to individuals of all ages and stages, particularly during pregnancy. The placenta is a temporary organ facilitating the connection between the mother and fetus. While it can detoxify certain exogenous substances, it is also vulnerable to the impacts of endocrine disruptors. Likewise, the intestinal flora is highly sensitive to exogenous stresses and environmental pollutants. The regulation of gut microbiota plays a crucial role in ensuring the health of both the mother and the fetus. The gut-placental axis connects the gut, gut microbes, placenta, and fetus. Exploring possible effects on placental function and fetal development involves analyzing changes in gut microbiota composition. Given that bisphenol A may cross the intestine and affect intestinal function, gut microorganisms, and their metabolites, as well as its potential impact on the placenta, resulting in impaired placental function and fetal development, this study aims to establish a link between bisphenol A exposure, intestinal microorganisms, placental function, and fetal development. This paper seeks to analyze the effects of maternal exposure to bisphenol A during pregnancy on the balance of the maternal gut microbiota, placental function, and fetal development, considering the key role of the gut-placental axis. Additionally, this paper proposes potential directions for future research emphasizing the importance of mitigating the adverse outcomes of bisphenol A exposure during pregnancy in both human and animal studies.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141788878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bisphenol M inhibits mouse oocyte maturation in vitro by disrupting cytoskeleton architecture and cell cycle processes 双酚 M 通过破坏细胞骨架结构和细胞周期过程抑制小鼠卵母细胞的体外成熟。

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-07-24 DOI: 10.1016/j.reprotox.2024.108667

{"title":"Bisphenol M inhibits mouse oocyte maturation in vitro by disrupting cytoskeleton architecture and cell cycle processes","authors":"","doi":"10.1016/j.reprotox.2024.108667","DOIUrl":"10.1016/j.reprotox.2024.108667","url":null,"abstract":"<div><p>Bisphenol M (BPM), an alternative to bisphenol A (BPA), is commonly utilized in various industrial applications. However, BPM does not represent a safe substitute for BPA due to its detrimental effects on living beings. This research aimed to assess the influence of BPM exposure on the in vitro maturation of mouse oocytes. The findings revealed that BPM exposure had a notable impact on the germinal vesicle breakdown (GVBD) rate and polar body extrusion (PBE) rate throughout the meiotic progression of mouse oocytes, ultimately resulting in meiotic arrest. Investigations demonstrated that oocytes exposure to BPM led to continued activation of spindle assembly checkpoint. Further studies revealed that securin and cyclin B1 could not be degraded in BPM-exposed oocytes, and meiosis could not realize the transition from the MI to the AI stage. Mechanistically, BPM exposure resulted in abnormal spindle assembly and disrupted chromosome alignment of oocytes. Additionally, abnormal positioning of microtubule organizing center-associated proteins implied that MTOC may be dysfunctional. Furthermore, an elevation in the acetylation level of α-tubulin in oocytes was observed after BPM treatment, leading to decreased microtubule stability. In addition to its impact on microtubules, BPM exposure led to a reduction in the expression of the actin, signifying the disruption of actin assembly. Further research indicated a heightened incidence of DNA damage in oocytes following BPM exposure. Besides, BPM exposure induced alterations in histone modifications. The outcomes of this experiment demonstrate that BPM exposure impairs oocyte quality and inhibits meiotic maturation of mouse oocytes.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Perinatal nicotine vaping exposure induces pro-myofibroblastic phenotype in rat bone marrow-derived mesenchymal stem cells 围产期尼古丁吸入诱导大鼠骨髓间充质干细胞的前肌成纤维细胞表型

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-07-24 DOI: 10.1016/j.reprotox.2024.108673

{"title":"Perinatal nicotine vaping exposure induces pro-myofibroblastic phenotype in rat bone marrow-derived mesenchymal stem cells","authors":"","doi":"10.1016/j.reprotox.2024.108673","DOIUrl":"10.1016/j.reprotox.2024.108673","url":null,"abstract":"<div><p>Perinatal nicotine exposure via tobacco smoking results in increased proclivity to chronic lung disease (CLD); however, the underlying molecular mechanisms remain incompletely understood. We previously demonstrated that in addition to nicotine’s direct effects on the developing lung, there are also adverse molecular alterations in bone marrow-derived mesenchymal stem cells (BMSCs), which are vital to lung injury repair. Whether perinatal nicotine exposure via electronic-cigarette (e-cig) vaping also adversely affects BMSCs is unknown. This is highly relevant due to marked increase in e-cig vaping including by pregnant women. Hypothesizing that perinatal nicotine exposure via e-cig vaping predisposes BMSCs to a pro-myofibroblastic phenotype, pregnant rat dams were exposed to fresh air (control), vehicle (e-cig without nicotine), or e-cig (e-cig with nicotine) daily during pregnancy and lactation. At postnatal day 21, offspring BMSCs were isolated and studied for cell proliferation, migration, wound healing response, and expression of key Wnt and PPARγ signaling intermediates (β-catenin, LEF-1, PPARγ, ADRP and C/EBPα) and myogenic markers (fibronectin, αSMA, calponin) proteins using immunoblotting. Compared to controls, perinatal e-cig exposure resulted in significant decrease in BMSC proliferation, migration, and wound healing response. The expression of key Wnt signaling intermediates (β-catenin, LEF-1) and myogenic markers (fibronectin, αSMA, calponin) increased significantly, while PPARγ signaling intermediates (PPARγ, ADRP, and C/EBPα) decreased significantly. Based on these data, we conclude that perinatally e-cig exposed BMSCs demonstrate pro-myofibroblastic phenotype and impaired injury-repair potential, indicating a potentially similar susceptibility to CLD following perinatal nicotine exposure via vaping as seen following parenteral perinatal nicotine exposure.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141767208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sitagliptin exhibits protective effects against methotrexate-induced testicular toxicity: The involvement of oxidative stress-related factors 西他列汀对甲氨蝶呤引起的睾丸毒性有保护作用：氧化应激相关因素的参与

IF 3.3 4区医学

Reproductive toxicology Pub Date : 2024-07-21 DOI: 10.1016/j.reprotox.2024.108672

{"title":"Sitagliptin exhibits protective effects against methotrexate-induced testicular toxicity: The involvement of oxidative stress-related factors","authors":"","doi":"10.1016/j.reprotox.2024.108672","DOIUrl":"10.1016/j.reprotox.2024.108672","url":null,"abstract":"<div><p>Methotrexate (MTX) is widely prescribed to treat different malignancies as well as autoimmune diseases. However, it causes a range of side effects in different organs such as testis. This study aims to clarify the role of dipeptidyl peptidase 4 (DPP4) in MTX-induced testicular damage via pathways involved in oxidative stress and evaluates the protective effects of sitagliptin as a DPP4 inhibitor. Twenty-four animals randomly allocated into four groups including: (I) control, (II) MTX (20 mg/kg, i.p.), (III) sitagliptin (20 mg/kg, i.p., for four consecutive days), and MTX + sitagliptin in which received chemicals resembling group II and III. Histopathological examinations conducted to assess the structural changes in testes of different experimental groups. Also, ELISA method employed to investigate the levels of DPP4, AKT, p-AKT, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1). In addition, the total malondialdehyde (MDA) content and the activity of superoxide dismutase (SOD) were assessed. The results indicated that MTX administration was accompanied with testicular damage, which reversed by sitagliptin treatment. The biochemical observations demonstrated that MTX markedly increased the levels of DPP4, decreased p-AKT/AKT ratio followed by a marked decrement in Nrf2 and HO-1 levels. Also, it was observed that MTX decreased the activity of SOD and increased total MDA content in testicular specimen. However, sitagliptin treatment diminished mentioned alterations effectively. Altogether, our findings supported the possible role of DPP4 in MTX-induced testicular toxicity along with the potential protective features of sitagliptin via suppressing of the histopathological and biochemical alterations induced by MTX.</p></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0