Journal of Molecular Histology最新文献

{"title":"Tetrandrine improves oxidative stress and pyroptosis of podocytes in diabetic kidney disease by regulating TXNIP/NLRP3/GSDMD signaling pathway","authors":"Lujun Tang,&nbsp;Liumei Yuan,&nbsp;Di Ren,&nbsp;Jiebin Huang,&nbsp;Renjie Liu,&nbsp;Zhiwei Xia,&nbsp;Na Huang,&nbsp;Shangbo Zhang","doi":"10.1007/s10735-025-10609-x","DOIUrl":"10.1007/s10735-025-10609-x","url":null,"abstract":"<div><p>Podocyte injury from oxidative stress and pyroptosis is closely linked with diabetic kidney disease (DKD). Here, Tetrandrine (TET), derived from tetrandrine root, with anti-inflammatory and antioxidant traits, was studied for its role in podocyte oxidative stress and pyroptosis in DKD. A rat model of DKD was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin (STZ). Renal function was assessed using urinary albumin to creatinine ratio (UACR), serum creatinine (Scr), and blood urea nitrogen (BUN) levels. Renal pathological morphology was evaluated by hematoxylin-eosin (HE) staining and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were detected with commercially available kits. DCFH-DA probe was used to detect intracellular ROS levels. Western blot detected pyroptosis-related proteins (TXNIP, NLRP3, GSDMD-N, pro-caspase-1). Inflammatory factors (IL-1β and IL-18) levels were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence staining observed the expression and localization of GSDMD. Administration of TET alleviated renal damage in rats with DKD. In DKD rats, TET suppressed the TXNIP/NLRP3/GSDMD pathway, leading to a decrease in oxidative stress and pyroptosis within the renal tissue. In vitro, by inhibiting the TXNIP/NLRP3/GSDMD signaling pathway, TET mitigated podocyte oxidative stress and pyroptosis triggered by high glucose. Following TXNIP overexpressing, podocyte oxidative stress and pyroptosis that TET initially suppressed were subsequently reversed. Our results reveal that TET represses podocyte oxidative stress and pyroptosis through TXNIP/NLRP3/GSDMD pathway, which provides new therapeutic targets for DKD treatment.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sesame oil ameliorates aspartame-induced immunotoxicity in mice: a hematological, antioxidative, and histopathological evaluation","authors":"Khola Basalat,&nbsp;Ata Ul Mustafa Fahad,&nbsp;Amber Zahid,&nbsp;Maryam Iqbal,&nbsp;Sara Tariq,&nbsp;Laraib Zahid","doi":"10.1007/s10735-025-10612-2","DOIUrl":"10.1007/s10735-025-10612-2","url":null,"abstract":"<div><p>Aspartame is a widely used non-nutritive sweetener suspected of having immunotoxic effects. This study evaluated the protective role of sesame oil against aspartame-induced toxicity in Swiss albino mice. Male Swiss albino mice were divided into four groups (n = 40): control, aspartame-treated (40 mg/kg/day), aspartame + sesame oil, and sesame oil alone. Over 60 days, aspartame (ASP) administration resulted in increased body weight, feed, and water intake, alongside a reduction in relative organ weights. Hematological analysis showed a significant decline in WBCs, eosinophils, and monocytes in the ASP group. Antioxidant activity (GSH, GPx) was significantly impaired in ASP-treated mice. Histopathological analysis revealed structural anomalies in both thymus and spleen, including capsular thickening, trabecular enlargement, white pulp degeneration, and increased apoptotic macrophages in the thymic cortex. Co-administration of sesame oil ameliorated these toxic effects, with notable improvements in organ morphology, hematological parameters, and histological integrity. Mice treated with sesame oil alone showed no significant deviations from control values. These findings suggest that sesame oil may offer protective effects against aspartame-induced immunotoxicity, possibly via its antioxidant properties.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div><div><p>Methodology of the experiment</p></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145129670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Moringa Oleifera mitigates oxidative stress and pancreatic toxicity induced by sodium valproate in female Sprague Dawley rats","authors":"Eda Dagsuyu,&nbsp;Pınar Koroglu,&nbsp;Umar Faruk Magaji,&nbsp;Ozlem Sacan,&nbsp;Omur Karabulut Bulan,&nbsp;Refiye Yanardag","doi":"10.1007/s10735-025-10600-6","DOIUrl":"10.1007/s10735-025-10600-6","url":null,"abstract":"<div><p>Sodium valproate (VPA, valproic acid) is one of the most frequently prescribed antiepileptic drugs. However, this drug is known to cause significant oxidative damage and toxicity in various tissues and organs, including pancreatic tissue. <i>Moringa oleifera</i> (M) is a plant with antioxidant, anti-inflammatory, and anticancer effects, whose consumption and properties have gained prominence in recent years. This study investigates the protective effects of ethanolic extract of <i>Moringa oleifera</i> leaves against VPA-induced pancreatic oxidative damage in a rat model. Four experimental groups (Control, M, VPA, and VPA + M) comprising female Sprague Dawley rats were evaluated through biochemical, histological, and immunohistochemical analyses. The Moringa extract (0.3 g/kg/day) and VPA (0.5 g/kg/day) were given for 15 days. Bioactive compounds such as quercetin, kaempferol, ascorbic acid in <i>Moringa oleifera</i> leaf were predicted via Dr. Duke’s Phytochemical and Ethnobotanical Database. According to our results, Moringa administration increased antioxidant enzyme activities after VPA-induced damage, while significantly decreasing lipid peroxidation, advanced oxidation protein products, and other oxidant species. Histological analysis revealed the cytoprotective effect of Moringa on pancreas tissue by reducing pancreatic histological damage and decreasing PCNA-positive cells in the VPA + M group. These findings indicate the protective potential of <i>Moringa oleifera</i> against VPA-induced oxidative stress and pancreatic toxicity.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145110530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic effects of Scutellaria baicalensis total flavonoids on metabolic syndrome in rats via modulation of PPARα and PPARγ signaling","authors":"Yang Zhou,&nbsp;Zhi-Ping Li,&nbsp;Yu-Hang Lian,&nbsp;Xin Gao,&nbsp;Song-He Yin,&nbsp;Yu-Mei Zhao","doi":"10.1007/s10735-025-10606-0","DOIUrl":"10.1007/s10735-025-10606-0","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of this study is to evaluate the therapeutic effects of <i>Scutellaria baicalensis</i> total flavonoids (STF) in a rat model of metabolic syndrome (MS), with particular focus on the core regulatory mechanisms contributing to metabolic homeostasis. Additionally, the modulation of peroxisome proliferator-activated receptors (PPARs) by STF was investigated to elucidate its molecular targets and associated features within the pathophysiology of MS. Metabolic syndrome was induced in Sprague Dawley rats through the administration of a high-fat/high-glucose diet combined with streptozotocin (STZ). STF was administered orally during the induction period. Serum levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG), and fasting insulin (FINS) were quantified. The homeostatic model assessment of insulin resistance (HOMA-IR) was calculated. Hepatic concentrations of TC and TG were also measured. Histopathological alterations were evaluated using hematoxylin and eosin (HE) staining, while hepatic lipid accumulation was assessed through Oil Red O staining. Hepatic expression levels of PPARα and PPARγ proteins were determined via Western blot analysis. Treatment with STF at doses of 50 and 100 mg·kg⁻¹ significantly reduced serum levels of TC, TG, LDL-C, FBG, FINS, and HOMA-IR, while preventing the decline in HDL-C levels among rats with MS. STF administration also alleviated abnormal liver weight and suppressed hepatic accumulation of TC and TG, accompanied by improvements in histological features. Western blot analysis revealed upregulation of hepatic PPARα and PPARγ protein expression following STF treatment. STF demonstrated the capacity to reduce body weight and improve lipid profiles and insulin resistance in rats with MS. These effects may be associated with the regulation of PPARα and PPARγ protein expression.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of Insulin-Induced umbilical cord stem cells on Seladin-1/APP/GFAP expression in rat hippocampal CA1/CA3 regions following chronic hypoxia","authors":"Gholamreza Hassanzadeh,&nbsp;Soheil Ashouri,&nbsp;Reza Kargar,&nbsp;Atefeh Shamosi,&nbsp;Simin Mahakizadeh","doi":"10.1007/s10735-025-10617-x","DOIUrl":"10.1007/s10735-025-10617-x","url":null,"abstract":"<div>\u0000 \u0000 <p>Dementia, a syndrome characterized by cognitive impairment, significantly impacts the global elderly population. Given their paracrine properties, mesenchymal stem cells (MSCs) represent a promising avenue for developing novel treatments for neurodegenerative disorders. Chronic hypoxia models Alzheimer’s disease-like pathology by triggering neuroinflammation and altering key biomarkers. This study evaluated the therapeutic potential of MSCs, insulin-induced MSCs, and insulin in a rat model of Alzheimer’s disease (AD). Forty-eight rats were allocated into eight experimental groups: normoxic control, sham-surgery control, and six hypoxic intervention groups (exposed to 8% O₂). Intraventricular administration of MSCs or insulin-induced MSCs, intranasal administration of insulin, or both insulin and MSCs were used in the intervention groups. Hypoxic exposure significantly elevated pro-inflammatory cytokines (IL-1β, TNF-α) and increased expression of glial fibrillary acidic protein (GFAP) and amyloid precursor protein (APP), while decreasing levels of the neuroprotective factor Seladin-1. Administration of MSCs or Ins-MSCs effectively mitigated these hypoxia-induced alterations. Specifically, treatment with MSCs or Insulin induced-MSCs restored Seladin-1, GFAP, and APP expression levels to those observed in normoxic controls. Furthermore, these treatments attenuated the hypoxia-associated increase in Nissl body pathology within the hippocampal pyramidal cell layer. The most pronounced therapeutic benefits were observed following combined intranasal insulin and intraventricular MSC administration. Consequently, the combinatorial approach of MSCs and insulin warrants further investigation as a potential therapeutic strategy for Alzheimer’s disease. Combining intranasal insulin with insulin-induced MSCs may offer a strategy to target multiple AD pathology pathways.</p>\u0000 </div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal cytokine profile on lipopolysaccharide-induced acute lung injury in mice","authors":"Jie Liang,&nbsp;Yaowei He,&nbsp;Xiaoxuan Chen,&nbsp;Lizhen Wang,&nbsp;Shaoxi Cai","doi":"10.1007/s10735-025-10610-4","DOIUrl":"10.1007/s10735-025-10610-4","url":null,"abstract":"<div><p>Acute lung injury (ALI) is a severe inflammatory condition marked by alveolar damage and cytokine dysregulation. Exosomes, as carriers of bioactive molecules, regulate immune responses through intercellular communication. However, the cytokine profile of serum-derived exosomes during ALI remains unclear, and their functional role in modulating inflammation is poorly defined. A murine model of ALI was established via intraperitoneal injection of lipopolysaccharide (LPS, 10 mg/kg), and samples were collected at 2 h and 8 h post-injection. Lung injury severity was assessed using hematoxylin and eosin staining and lung W/D weight ratio. Serum-derived exosomes were isolated using the ExoQuick precipitation method and characterized by transmission electron microscopy and western blotting. Cytokine and chemokine profiles were quantified using a 32-plex Luminex xMAP assay. Exosome-mediated immune modulation was evaluated through a scratch migration assay in RAW264.7 macrophages. LPS treatment led to increased pulmonary edema and histopathological damage, which were more pronounced at 8 h. A total of 14 cytokines in the serum, including IL-6, TNF-α, and MCP-1, were significantly elevated at either 2–8 h compared to the control group. However, chemokines such as IP-10, G-CSF, and MIP-1β were markedly upregulated in serum-derived exosomes from ALI mice. Functional assays demonstrated that exosomes from ALI mice significantly enhanced the migratory capacity of RAW264.7 macrophages. This study demonstrates that serum-derived exosomes from ALI mice are enriched in specific chemokines and promote macrophage migration in vitro. These findings suggest that exosomes may participate in inflammatory cell recruitment during ALI and hold potential as biomarkers or modulators in the inflammatory response.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling the persistent renal impact of intrauterine growth restriction and catch-up growth: integrating morphological insights with metabolomic profiling","authors":"Mukaddes Esrefoğlu,&nbsp;Fatmanur Koktasoglu,&nbsp;Nihan Bayindir,&nbsp;Fatma Bedia Karakaya Cimen,&nbsp;Seda Kirmizikan,&nbsp;Emine Rumeysa Hekimoglu,&nbsp;Somer Bekiroglu,&nbsp;Sahabettin Selek","doi":"10.1007/s10735-025-10616-y","DOIUrl":"10.1007/s10735-025-10616-y","url":null,"abstract":"<div><p>The study aimed to investigate the long-term effects of IUGR and consequent catch-up growth on metabolic health by using a comprehensive approach that included histopathological, immunohistochemical, biochemical, and metabolomics analyses. Sprague–Dawley pregnant rats either undergo bilateral uterine artery ligation or a sham surgery on the 19th day of gestation. The offspring reached catch-up growth, kidney samples were collected at postnatal weeks 2, 4, and 8 for analysis. IUGR rats exhibited a spectrum of changes including reduced glomeruli number, proliferating cell number, altered oxidative stress markers, various enzymes involved in Krebs cycle, mitochondrial dynamics, and energy metabolism. Examination of the 8-week-old cohort identified a broader spectrum of metabolic alterations, notably in the biosynthesis of phenylalanine, tyrosine, and tryptophan, phenylalanine, tyrosine, glyoxylate, dicarboxylate, pyruvate, alanine, aspartate, and glutamate metabolism, glycolysis/gluconeogenesis and citrate (TCA) cycle. Our metabolomics analysis provides insights into the potential disease susceptibility of individuals born with IUGR, including obesity, diabetes, hypertriglyceridemia, cardiovascular diseases, and mental retardation. These findings underscore the intricate interplay between intrauterine conditions and long-term metabolic health outcomes, highlighting the need for further investigation into preventive and therapeutic strategies to mitigate the risk of metabolic diseases in individuals with a history of IUGR.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LOXL1-AS1 suppresses ferroptosis in cervical cancer through m6A-dependent regulation of TFRC","authors":"Hongyou Wang,&nbsp;Jianbo Zhou,&nbsp;Jianfeng Zhang,&nbsp;Wenlei Yao,&nbsp;Haiyang Li,&nbsp;Kangjie Xu,&nbsp;Hui Cheng","doi":"10.1007/s10735-025-10603-3","DOIUrl":"10.1007/s10735-025-10603-3","url":null,"abstract":"<div><p>Transferrin receptor (TFRC) is essential for iron uptake and may regulate ferroptosis, a form of iron-dependent cell death implicated in cervical cancer (CC). Bioinformatic analyses (GEPIA, UALCAN, SRAMP, starBase) were combined with in vitro and in vivo experiments. CC cell lines were transfected with shRNAs or overexpression plasmids targeting TFRC and LOXL1-AS1. Proliferation was assessed by colony formation, EdU staining, and Ki-67 immunostaining. Ferroptosis was evaluated by measuring malondialdehyde (MDA), lipid ROS, Fe²⁺, and ferroptosis-related proteins. RNA pull-down, RIP, and MeRIP assays were used to explore m6A-dependent regulation, and actinomycin D assays assessed mRNA stability. TFRC and LOXL1-AS1 were upregulated in CC and associated with poor prognosis. TFRC promoted CC cell proliferation and inhibited ferroptosis. LOXL1-AS1 positively regulated TFRC by stabilizing its mRNA via an m6A-IGF2BP2-dependent mechanism. Rescue experiments confirmed that TFRC overexpression reversed the effects of LOXL1-AS1 knockdown. In vivo, LOXL1-AS1 depletion suppressed tumor growth and enhanced ferroptosis. LOXL1-AS1 promoted CC progression by stabilizing TFRC mRNA through m6A-IGF2BP2 interaction, suppressing ferroptosis. Targeting the LOXL1-AS1/IGF2BP2/TFRC axis may offer a potential therapeutic strategy for CC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145078839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine architecture of caprine pancreas: a histomorphochemical and ultrastructural study","authors":"Kapil Dharmesh,&nbsp;Varinder Uppal,&nbsp;Anuradha Gupta,&nbsp;Devendra Pathak,&nbsp;Neelam Bansal","doi":"10.1007/s10735-025-10605-1","DOIUrl":"10.1007/s10735-025-10605-1","url":null,"abstract":"<div><p>This study aimed to study architecture of pancreatic islets by histological, ultrastructural, histochemical, and immunohistochemical investigations in male and female goats. The tissues were collected from different lobes of pancreas from local slaughterhouses and processed for paraffin sectioning. The sections were stained with different histomorphological, histochemical and immunohistochemical staining. For electron microscopy standard protocols were used. The study revealed no morphological differences in islets of male and female pancreas, however significantly larger (<i>p</i> &lt; 0.05) islets were observed in male animals. Among the different lobes larger islets were observed in left lobe in both the sexes. Immunohistochemically, number of insulin positive cells were more in female than male and number of glucagon cells were more in male than female but the difference was non significant (<i>p</i> &gt; 0.05). Low to moderate PCNA expression in both the sexes indicative of cellular proliferation within islets, while strong VEGF reactivity suggested its role in islet vascularization. This study has provided a baseline anatomical and immunohistochemical data for comparative endocrinology and disease models studies across species, especially in ruminants or domestic animals. Future study can help in early identification of sex-specific susceptibility to metabolic or endocrine disorders in goats (e.g., diabetes-like conditions).</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium benzoate exposure disrupts HPG-axis in male rats: insights into oxidative stress, hormonal dysregulation, histopathology and kisspeptin/RFRP-3 expression","authors":"Safdar Khan,&nbsp;Mohammad Attaullah,&nbsp;Sarwat Jahan,&nbsp;Rahmat Ali,&nbsp;Hira Zubair,&nbsp;Naila Hamayoun","doi":"10.1007/s10735-025-10611-3","DOIUrl":"10.1007/s10735-025-10611-3","url":null,"abstract":"<div><p>The reproductive effects related to sodium benzoate (SB) are increasingly recognized as concerns for public health. To elucidate the underlying mechanistic pathway in SB-induced reproductive impairment, we evaluated its dose-dependent effects by assessing the key elements of HPG- axis, encompassing wide range of doses from dietary to presumably harmful levels. Thirty-five adult male rats (Sprague-Dawley) split into seven groups (<i>n</i> = 5/group); control, SB10, SB50, SB100, SB500, SB1000mg/kg and the co-treated group (SB + EB). SB and distilled water were gavage for 90 consecutive days. The co-treated group received SB500 from day one, while estradiol benzoate (EB; 40 µg/kg) was given at mid-study onward till completion of experiment. Biochemical parameters, sperm parameters, reproductive hormones, gonadal histopathology, hypothalamic kisspeptin and RFRP-3 expression were assessed. SB produced a concentration-dependent reduction in the testis, accessary sex organs weight, antioxidant activities (SOD, POD, CAT and GSH), testosterone and FSH levels. Testicular ROS, TBARs and plasma LH levels were significantly raised compared to control. Fertility parameters underwent a significant decline in SB rats. Notably, kisspeptin showed dose-related decline, while RFRP-3 upregulated in SB rats. Morphometric indices of seminiferous tubules highlighted apparent alterations and marked traces of histopathology were noticed in test groups. EB treatment restored kisspeptin hence stabilized hormones and improved fertility parameters were seen in co-treated rats. SB exposure significantly disrupts HPG-axis via neuroendocrine dysregulation and inducing testicular cytotoxicity, with oxidative stress serve as the key mediator of these effects. It underscores the dire need for careful usage and future studies of its long-term reproductive safety.</p><h3>Graphical abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 5","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145073734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}