Gracieli Prado Elias, Haylla de Faria Horta, Alanna Ramalho Mateus, Laura Valentina Borges Pes, Adrielle Ouchi Lopes, Fernando Chiba, Alberto Carlos Botazzo Delbem, Kikue Takebayashi Sassaki, Roberta Okamoto, Cristina Antoniali
{"title":"MMP-9 expression in rat pup incisor teeth is not altered by maternal hypertension or maternal atenolol treatment during pregnancy and lactation","authors":"Gracieli Prado Elias, Haylla de Faria Horta, Alanna Ramalho Mateus, Laura Valentina Borges Pes, Adrielle Ouchi Lopes, Fernando Chiba, Alberto Carlos Botazzo Delbem, Kikue Takebayashi Sassaki, Roberta Okamoto, Cristina Antoniali","doi":"10.1007/s10735-024-10294-2","DOIUrl":"10.1007/s10735-024-10294-2","url":null,"abstract":"<div><p>Hypertension alters tooth formation and Atenolol reduces the blood pressure of spontaneously hypertensive rats (SHR) during pregnancy and lactation, and as demonstrated before, increases the microhardness of the SHR offspring’s teeth. MMP-9 is overexpressed in different tissues of hypertensive animals and treatment of hypertension substances can reverse this alteration. We hypothesize hypertension alters the expression of MMP-9 in dental structures of SHR offspring and that treating female SHR with atenolol prevents this alteration. This study aimed to evaluate the expression of matrix metalloproteinase (MMP-9) in incisor teeth (IT) in male offspring of SHR (30 days old) treated or untreated with Atenolol during pregnancy and lactation. MMP-9 expression was evaluated in ameloblasts (AM), enamel matrix (EM), odontoblasts (OD), and predentin (PD) of IT through immunohistochemical reactions (immunoperoxidase). Data were analyzed by Shapiro-Wilk and Kruskal-Wallis (<i>p</i> < 0.05), with Dunn post-test. Histological differences were not observed between IT tissues of SHR and normotensive Wistar rats. For the first time, our data showed that MMP-9 expression in specific dental structures is not altered in SHR. Atenolol treatment increased MMP-9 immunostaining in EM of Wistar rat, however, Atenolol did not alter MMP-9 in the IT tissues of SHR. Our results demonstrated that MMP-9 expression in dental tissues is not affected by hypertension or atenolol treatment in dental tissues. If confirmed in humans, the results obtained in this study will corroborate the suggestion that MMP-9 is not a viable therapeutic target for the treatment of dental alterations associated with maternal hypertension.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737298","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}
Esma Kirimlioglu, Alexandra Cernomorcenco, Ertan Katirci
{"title":"Ovarian expression of MerTK and its ligand Pros1 in non-pregnant estrus and pregnant mice","authors":"Esma Kirimlioglu, Alexandra Cernomorcenco, Ertan Katirci","doi":"10.1007/s10735-024-10292-4","DOIUrl":"10.1007/s10735-024-10292-4","url":null,"abstract":"<div><h3>Aim</h3><p>The interaction of MerTK, which negatively regulates immune responses, with its ligand Pros1 contributes to the resolution of apoptosis and inflammation, participating in the healing process of tissues. The levels of MerTK and Pros1, intensely expressed in macrophages (Mϕs), are affected by sex hormones. The expression levels of these proteins in Mϕs, which have a role in corpus luteum (CL) development or regression and folliculogenesis, were investigated in this study since their expressions have not been evaluated in pregnant mouse ovaries.</p><h3>Method</h3><p>We analyzed mouse ovaries from non-pregnant mice at estrus and gestation days 5, 8, and 15 (each n:10). We used qPCR to evaluate <i>Mertk</i> and <i>Pros1</i> mRNA levels and assessed their protein expression and localization using immunohistochemistry and double immunofluorescence staining for co-localization.</p><h3>Results</h3><p>Mertk and Pros1 mRNA and protein levels significantly increased in GD15. MerTK and Pros1 protein levels in mouse CL on GD15 were significantly higher than all other groups. MerTK and Pros1 positive Mϕs were observed in CL of GD15 by double immunofluorescence. MerTK protein levels were increased in granulosa cells GD15 of primary and growing follicles.</p><h3>Conclusion</h3><p>Our study revealed for the first time that the expression of MerTK and Pros1 was significantly increased in CL at GD15 in mice. These results suggest that increased levels of MerTK andPros1 may enhance their interaction as receptor-ligand binding partners in CL potentially contributing to the balance of apoptosis and inflammation.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s10735-024-10292-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CircKRT75 augments the cisplatin chemoresistance of nasopharyngeal carcinoma via targeting miR-659/CCAR2 axis","authors":"Xiaoli Li, Yujie Deng, Zhaosheng Yin","doi":"10.1007/s10735-024-10287-1","DOIUrl":"10.1007/s10735-024-10287-1","url":null,"abstract":"<div><p>Cisplatin resistance is a clinical challenge limiting the treatment of nasopharyngeal carcinoma (NPC). CircRNAs have been evidenced as key molecules involved in tumor advancement and drug resistance. The present study aimed to elucidate the potential biological value of circKRT75 in NPC cisplatin resistance. CircKRT75 levels in NPC clinical samples and parental/resistant cell lines were analyzed based on qRT-PCR. CCK-8 and flow cytometry were adopted to assess the impacts of circKRT75 on the growth viability and apoptotic ability of NPC resistant cells. Meanwhile, western blot was performed to detect changes in the expression of apoptosis-related proteins. Bioinformatics analysis predicted miRNAs and mRNAs downstream of circKRT75, and the interaction between circKRT75 and downstream targets was validated by RNA pull-down, dual-luciferase reporter and rescue experiments. CircKRT75 was notably enhanced in NPC tissues and NPC cisplatin-resistant cells. Functional experiments disclosed that circKRT75 silencing repressed NPC-resistant cell growth and promoted apoptosis. Bioinformatics screening identified that circKRT75 performed as a molecular sponge for miR-659, and CCAR2 was a direct target of miR-659. Further rescue assays confirmed that miR-659 inhibitor restored the inhibitory effect of circKRT75 knockdown on the growth of drug-resistant cells, while CCAR2 silencing could reverse the promotion of NPC cisplatin resistance by circKRT75 upregulation. Additionally, animal experiments revealed that circKRT75 knockdown restrained NPC cisplatin resistance in vivo. CircKRT75 contributed to cisplatin resistance in NPC through miR-659/CCAR2 signaling, which provided a novel perspective and direction to solve the problem of chemoresistance in NPC.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737296","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":"Bone marrow mesenchymal stem cells-derived exosomes promote spinal cord injury repair through the miR-497-5p/TXNIP/NLRP3 axis","authors":"JiXu Xu, Jun Zhang, QiaoYun Liu, Bin Wang","doi":"10.1007/s10735-024-10289-z","DOIUrl":"10.1007/s10735-024-10289-z","url":null,"abstract":"<div><p>Bone marrow mesenchymal stem cells (BMSCs) indicate a repairing prospect to treat spinal cord injury, a major traumatic disease. This study investigated the repair effect of bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos) on spinal cord injury. BMSCs were collected to extract BMSC-Exos which were identified by different means. The SCI model of rats was established, the motor behavior was scored by BBB field test, and the spinal cord tissues were separated and stained by HE, Nissl, and Tunel, respectively, as well as analyzed to measure inflammatory and oxidative stress responses. PC12 cells were co-cultured with Exos and analyzed by CCK-8 and flow cytometry to measure cell proliferation and apoptosis. BMSC-Exos improved SCI in rats with the recovery of motor function, alleviation of pathological conditions, and reduction of apoptosis, inflammatory responses, and oxidative stress. BMSC-Exos increased miR-497-5p expression, and miR-497-5p overexpression strengthened the protective effect of BMSC-Exos on SCI. miR-497-5p targeted inactivation of TXNIP/NLRP3 pathway. TXNIP saved the repair effect of miR-497-5p-carrying BMSC-Exos on SCI rats. miR-497-5p-carrying BMSC-Exos alleviated apoptosis and induced proliferation of H<sub>2</sub>O<sub>2</sub>-treated PC12 cells. BMSC-Exos promote SCI repair via the miR-497-5p/TXNIP/NLRP3 axis, which may be a target for alleviating SCI-associated nerve damage.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749778","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":"Endometrioid tubal intraepithelial neoplasia (E-TIN): case report & literature review","authors":"Sadaf Muzaffar, Shireen R. Abdullah","doi":"10.1007/s10735-024-10282-6","DOIUrl":"10.1007/s10735-024-10282-6","url":null,"abstract":"<div><p>An endometrioid carcinogenic pathway of the fallopian tube with possible potential precursors including type II SCOUTs (secretory cell outgrowths) and E-TIN (endometrioid tubal intraepithelial neoplasia) has been recently documented. We report an incidental focus of E-TIN identified in a hysterectomy specimen for Grade 1 endometrioid type endometrial carcinoma. The lesion was present at the fimbriated end of left fallopian tube involving 1 plica. It comprised crowded glandular proliferation with a pseudostratified columnar lining. The cells displayed elongated nuclei with no remarkable nuclear atypia.</p><p>Immunohistochemistry showed patchy loss of PAX 2 expression with multifocal aberrant nuclear and cytoplasmic staining for B-catenin. p53 was wild-type and ER was positive.</p><p>In view of the co-existing endometrioid type endometrial carcinoma, a possible metastatic spread to the fallopian tube was considered. However, morphologically no obvious nuclear atypia noted, and no associated inflammatory response or desmoplastic stromal reaction identified within the tubal lesion. And on immunostaining, the endometrial tumour was distinct from the tubal lesion. For instance, PTEN was negative/lost in the endometrial tumour but retained in the tubal lesion and B-catenin was membranous in the endometrial tumour but aberrant with multifocal nuclear and cytoplasmic overexpression in the tubal lesion. WT1 was negative in the endometrial tumour but positively expressed by the tubal lesion. All the above findings favoured the possibility of the tubal lesion as being independent of the endometrial primary. In conclusion, we describe an incidental B-catenin aberrant endometrioid type proliferation of the fallopian tube/E-TIN, to raise awareness of such lesions.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737036","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":"Ameliorative effects of Edaravone against Valproic Acid-Induced kidney damage","authors":"Bertan Boran Bayrak, Serap Sancar, Neziha Hacihasanoglu Cakmak, Sehnaz Bolkent, Refiye Yanardag","doi":"10.1007/s10735-024-10291-5","DOIUrl":"10.1007/s10735-024-10291-5","url":null,"abstract":"<div><p>Valproic acid (VPA) is a well-known and increasingly documented antiepileptic drug that has been widely used in the treatment of epilepsy and/or epilepsy-related disorders. Prolonged clinical use of VPA has been reported to cause side effects such as nephrotoxicity. Edaravone (EDA) is a powerful free radical scavenger. The aim of the study was to investigate the protective effects of EDA against VPA-induced oxidative renal injury. Four experimental groups were formed by randomly assigning thirty-eight male Sprague Dawley rats. The first group, (Control Group, <i>n</i> = 8), consisted of healthy rats. The second group, (Group II, <i>n</i> = 10), comprised control rats given intraperitoneally EDA (30 mg/kg/day) for seven days. The third group (Group III, <i>n</i> = 10) was administered intraperitoneally only VPA (500 mg/kg/day) for seven days. The last group (Group IV, <i>n</i> = 10) was treated with VPA + EDA for seven days. On the 8th day, kidney tissues were immediately removed from rats. In kidney homogenates, reduced glutathione levels and Na/K<sup>+</sup>-ATPase, paraoxonase1 and prolidase activities were remarkably decreased while catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, myeloperoxidase, and xanthine oxidase activities and lipid peroxidation, protein carbonyl, advanced oxidized protein products, and hydroxyproline contents were notably elevated in VPA given group. Consistently, administration of EDA decreased renal degenerative changes seen in the kidney tissue of VPA given rats. Treatment with EDA in the VPA group significantly resulted in the recovery of both biochemical and histopathological alterations. As a result, EDA is potentially beneficial to revert oxidative renal damage induced by VPA.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714650","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}
Guanrong Ma, Zhiqi Chen, Lanxi Wang, Xiulin Chang, Liaoqiong Fang, Jin Bai
{"title":"Study on the biosafety and targeting efficiency of Escherichia coli outer membrane vesicles in breast tumor","authors":"Guanrong Ma, Zhiqi Chen, Lanxi Wang, Xiulin Chang, Liaoqiong Fang, Jin Bai","doi":"10.1007/s10735-024-10296-0","DOIUrl":"10.1007/s10735-024-10296-0","url":null,"abstract":"<div><p>To seek out the targeting of <i>Escherichia coli</i> outer membrane vesicles (<i>E. coli</i> OMVs) in breast tumor-bearing mice and their biosafety in healthy mice. Ultrafiltration in conjunction with ultracentrifugation was utilized to concentrate <i>E. coli</i> OMVs, and characterize them. Subcutaneous breast tumors were induced in BALB/c mice to serve as an experimental model, and the biodistribution of <i>E. coli</i> OMVs in both tumor-bearing and healthy mice was monitored using an in vivo fluorescence imaging system. Utilizing frozen sections, the infiltration of <i>E. coli</i> OMVs in tumor tissues was appraised at the 24-hour post-injection. Healthy BALB/c mice were randomly divided into control group and vesicles group. Following the intravenous injection of <i>E. coli</i> OMVs, monitoring encompassed variations in body weight, blood routine indices, serum levels of AST, ALT, and BUN, organ indices (heart, liver, spleen, lung, and kidney), along with tissue histopathology over a 14-day period. The spherical <i>E. coli</i> OMVs had a diameter of (155.8 ± 3.1) nm and exhibited the expression of outer membrane proteins OmpA and OmpC. Upon assessment, it was evident that the <i>E. coli</i> OMVs persisted in the tumor tissues even 24 h post-injection. An evident decrease in the body weight of the vesicles group, distinct from the control group, was observed on the second day after injection (<i>P</i> < 0.001); in contrast, no considerable differences were noted at subsequent time points (<i>P</i> > 0.05). Following the injection, the vesicles group displayed notable reductions in WBC and PLT as relative to the control group (<i>P</i> < 0.0001) on the initial day, however, there were no noteworthy distinctions as opposed to the control group for other hematological indices; No notable variances in hematological indices between the two groups were observed on the seventh and fourteenth day (<i>P</i> > 0.05). Over the 14 days, no substantial differences were observed in the serum levels of BUN, AST, ALT, and organ indices within the vesicles group as opposed to the control group (<i>P</i> > 0.05). Furthermore, there were no obvious abnormal changes in tissue morphology. 0.5 mg/kg of <i>E. coli</i> OMVs can safely and effectively target 4T1 breast tumor in mice.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714651","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}
Viktor Eustáquio Ferreira Vilaça da Silveira, Gabriel Aurélio Ferraz Veneno, Lívia Lorrayne Ribeiro da Silva, Nilo Bazzoli, Alessandro Loureiro Paschoalini
{"title":"Effects of glyphosate-based herbicide on target organs of Astyanax altiparanae in different treatments","authors":"Viktor Eustáquio Ferreira Vilaça da Silveira, Gabriel Aurélio Ferraz Veneno, Lívia Lorrayne Ribeiro da Silva, Nilo Bazzoli, Alessandro Loureiro Paschoalini","doi":"10.1007/s10735-024-10299-x","DOIUrl":"10.1007/s10735-024-10299-x","url":null,"abstract":"<div><p>Glyphosate-based herbicides are extensively utilized in Neotropical agriculture for weed control. Despite their widespread application, concerns regarding water contamination and its consequential impacts on aquatic organisms persist. Notably, there remains a dearth of studies investigating the effects of glyphosate on Neotropical fish species. This study aimed to address this gap by investigating the morphophysiological effects of this herbicide on the liver, gills, and ovaries of <i>Astyanax altiparanae</i>, an ecological and economically important neotropical fish species. Forty individuals were acclimated for 15 days before being exposed to different concentrations of glyphosate (65, 280, and 1000 µg/L) for 28 days. Histological and histometric analyses were conducted on liver, gill, and ovary samples. The findings revealed significant alterations in fish physiology following exposure to glyphosate. The hepatosomatic index increased markedly across all concentration levels, accompanied by dilation of hepatic sinusoidal capillaries, particularly pronounced at higher concentrations. Gill samples exhibited congestion in the central venous sinus, lamellar fusion, and cell death. Additionally, the exposed fish showed a decrease in gonadosomatic index, and the mature females an increase in pre-vitellogenic follicles and a decrease in vitellogenic follicles. This study detected adverse morphophysiological impacts of glyphosate-based herbicides on <i>A. altiparanae</i>, even at permitted concentrations. These findings emphasize the necessity for further research and improved management strategies to mitigate environmental risks associated with herbicide use in aquatic ecosystems.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714630","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}
Wasim Akram, Abul Kalam Najmi, Syed Ehtaishamul Haque
{"title":"Levocabastine ameliorates cyclophosphamide-induced hepatotoxicity in Swiss albino mice: modulation of Nrf2, NF-κB p65, cleaved caspase-3 and TGF-β signaling molecules","authors":"Wasim Akram, Abul Kalam Najmi, Syed Ehtaishamul Haque","doi":"10.1007/s10735-024-10286-2","DOIUrl":"10.1007/s10735-024-10286-2","url":null,"abstract":"<div><h3>Background</h3><p>Cyclophosphamide (CP)-induced hepatotoxicity is a significant problem in clinical settings. This study aimed to evaluate the protective effect of levocabastine (LEV) on CP-induced hepatotoxicity in Swiss albino mice.</p><h3>Methods and results</h3><p>Mice were given CP (toxic drug) 200 mg/kg, i.p., once on the 7th day, and LEV 50 and 100 µg/kg, i.p., and fenofibrate (FF) 80 mg/kg, p.o., daily for 14 days. On the 15th day, blood and liver samples were collected to assess biological parameters. CP 200 mg/kg caused hepatotoxicity due to oxidative stress, inflammation, apoptosis, and fibrosis as manifested by a reduction in catalase, reduced glutathione (GSH), superoxide dismutase (SOD), and an increase in thiobarbituric acid reactive substance (TBARS), nitrite, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-β1), interleukin-1β (IL-1β), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels. Cleaved caspase-3 and nuclear factor kappa-B (NF-κB) expression was also increased and nuclear factor erythroid 2-related factor (Nrf2) expression was decreased as confirmed by Immunohistochemical analysis. It also caused histopathological abnormalities and fibrosis as manifested by Hematoxylin-Eosin (H&E) and Masson’s trichrome (MT) staining. These alterations were returned to almost normal when treated with LEV 100 µg/kg and FF 80 mg/kg. Thus, LEV protected CP-induced hepatotoxicity by reversing inflammation, apoptosis, fibrosis, oxidative stress, hepatic injury, and histopathological damages.</p><h3>Conclusion</h3><p>LEV can be helpful as an adjuvant in cancer patients who are on CP treatment, to minimize toxicity. However, its role in in-vivo cancer model is further needed to be confirmed.</p></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714649","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}
Leila Rezaie Shirmard, Saleh Khezri, Sara Ahadzadeh, Paniiiz Azadimoghaddam, Sepideh Azizian, Ahmad Salimi
{"title":"Preparation of gallic acid-loaded chitosan nanoparticles and their chemoprotective effects on N-ethyl-N-nitrosourea-induced hepatotoxicity and mortality in rats","authors":"Leila Rezaie Shirmard, Saleh Khezri, Sara Ahadzadeh, Paniiiz Azadimoghaddam, Sepideh Azizian, Ahmad Salimi","doi":"10.1007/s10735-024-10280-8","DOIUrl":"10.1007/s10735-024-10280-8","url":null,"abstract":"<div><p>N-ethyl-N-nitrosourea (ENU) as n-nitrosamine and alkylating agent, ubiquitous within living cells and in the environment can act as a full carcinogen and induce tumor formation in various tissues such as liver. In this study, gallic acid-loaded chitosan nanoparticles (GANPs) were synthesized and evaluated for their chemopreventive effect against ENU-induced hepatotoxicity and mortality in rats. Twenty-four male Wistar rats were divided into four groups including: control, ENU (single doses of 50 mg/kg via intraperitoneal injection), GA + ENU and GANPs + ENU. Animals were orally pretreated with GA (50 mg/kg) and GANPs (50 mg/kg) for 30 days, and liver injuries induced by ENU on the 31st day of study. After ENU administration, weight changes and mortality were monitored during 30 days, and then the animals were sacrificed and alpha-fetoprotein (AFP) as a tumor marker, liver function tests (ALT, AST and ALP), oxidative stress markers (GSH and MDA), mitochondrial toxicity parameters, and histopathological assessment were evaluated. Except for AFP and MDA, ENU caused significant elevation of liver enzymes, mitochondrial ROS formation, collapse of mitochondrial membrane potential depletion of GSH, histopathological abnormalities and mortality in rats. Our data showed that GANPs significantly increased the survival of rats by up to 66%, delayed in death time and prevented weight changes after exposure to ENU. Moreover, GANPs restored liver enzyme levels, ROS formation, mitochondrial dysfunction, GSH levels, and histopathological abnormalities towards normal. Our findings suggest that GANPs revealed a significant protective effect against deadly toxicity induced by ENU as an alkylating full carcinogen agent in liver tissue.</p><h3>Graphical Abstract</h3>\u0000<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":650,"journal":{"name":"Journal of Molecular Histology","volume":"56 1","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708723","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}