Journal of Biochemical and Molecular Toxicology最新文献

{"title":"EMP1 knockdown mitigated high glucose-induced pyroptosis and oxidative stress in rat H9c2 cardiomyocytes by inhibiting the RAS/RAF/MAPK signaling pathway","authors":"Ying Han,&nbsp;Jin Gong,&nbsp;Min Pan,&nbsp;Zhoufei Fang,&nbsp;Xiaowen Ou,&nbsp;Wenqin Cai,&nbsp;Xiane Peng","doi":"10.1002/jbt.70002","DOIUrl":"https://doi.org/10.1002/jbt.70002","url":null,"abstract":"<p>The purpose of this study was to investigate the mechanism of EMP1 action in high glucose (HG)-induced H9c2 cardiac cell pyroptosis and oxidative injury. Rat cardiomyocytes H9c2 were exposed to 33 mM glucose for 24, 48, or 72 h to induce cytotoxicity. EMP1-siRNA, NLRP3 agonist Nigericin, and pcNDA-RAS were used to treat H9c2 cells under HG conditions. Cell Counting Kit (CCK)-8 assay showed that cell proliferation was decreased following HG induction, which was rescued by EMP1 knockdown. Our results also suggested that EMP1 siRNA transfection significantly decreased the apoptosis and pyroptosis of HG-induced cells, as indicated by the reduction of NLRP3 IL-1β, ASC, GSDMD, cleaved-caspase1 and cleaved-caspase3 levels in HG-induced H9c2 cells. In addition, EMP1 knockdown alleviated HG-induced mitochondrial damage and oxidative stress in H9c2 cells. NLRP3 activation reversed the inhibitory effects of EMP1 knockdown on pyroptosis and oxidative stress in HG-induced H9c2 cells. Mechanistically, we found that EMP1 knockdown suppressed the RAS/RAF/MAPK signaling pathway in HG-induced H9c2 cells. RAS overexpression blocked the protective effect of EMP1 knockdown on HG-induced H9c2 cell apoptosis, pyroptosis, and oxidative injury. Our findings suggest that EMP1 knockdown treatment might provide a novel therapy for diabetic cardiomyopathy.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447846","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}

{"title":"Correction to RETRACTION: The cardioprotective effects of a combination of quercetin and α-tocopherol on isoproterenol-induced myocardial infarcted rats","authors":"","doi":"10.1002/jbt.23866","DOIUrl":"https://doi.org/10.1002/jbt.23866","url":null,"abstract":"<p>“RETRACTION: The Cardioprotective Effects of a Combination of Quercetin and α-Tocopherol on Isoproterenol-induced Myocardial Infarcted Rats,” <i>Journal of Biochemical and Molecular Toxicology</i> 38, no. 10 (2024): e23857, https://doi.org/10.1002/jbt.23857.</p><p>In the previously published retraction note, the reasons for the retraction were described inaccurately, and the authors' disapproval of the retraction was not reflected. This has now been addressed and corrected below.</p><p>The retraction has been agreed following an investigation into concerns raised by a third party, which revealed that some of the bands presented in the agarose gel electrophoresis in Figure 2 have been published in another article by one of the same authors. The gels in the two articles represent different experiments. The authors did not provide a satisfactory explanation or their original data. The editors consider the results and conclusion reported in this article unreliable. The authors disagree with the retraction.</p><p>We apologize for this error.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.23866","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443478","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":"SPAG4 enhances mitochondrial respiration and aerobic glycolysis in colorectal cancer cells by activating the PI3K/Akt signaling pathway","authors":"Jiehao Zhou,&nbsp;Haobo Sun,&nbsp;Hang Zhou,&nbsp;Ying Liu","doi":"10.1002/jbt.70009","DOIUrl":"https://doi.org/10.1002/jbt.70009","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Aerobic glycolysis plays a pivotal role in the progression of tumors. Previously, a glycolysis-associated prognostic model in CRC was constructed and the glycolysis-related gene SPAG4 was discovered to be upregulated in CRC and was correlated with adverse prognosis. To date, however, no study has elucidated the specific role of SPAG4 in the development of CRC. In our study, CRC cells were transfected with si-SPAG4 or OE-SPAG4 to evaluate the influence of SPAG4 silencing or overexpression on CRC cell malignant behaviors. CRC cell proliferation and metastasis were detected via CCK-8, colony formation, and Transwell assays. The oxygen consumption rate and extracellular acidification rate of CRC cells were determined by using an XF24 extracellular flux analyzer. The expression of SPAG4, key mitochondrial markers (NDUFA1, SDHB, ATP5A, and PGC-1α), key enzymes involved in glycolysis (GLUT1, HK2, LDHA, PKM2, and PFK1), and PI3K/Akt pathway-molecules and downstream transcription factor HIF-1α was assessed by RT-qPCR and western blot analysis. SPAG4 expression in CRC and normal tissue samples was tested through immunohistochemical staining. Finally, SPAG4-overexpressed CRC cells were treated with LY294002 to validate the inhibition of PI3K/Akt pathway on CRC cell malignant phenotypes. Our results showed that SPAG4 was upregulated in CRC cells and tissues, and high expression SPAG4 predicted shorter overall survival time. SPAG4 knockdown inhibited while SPAG4 overexpression enhanced CRC cell proliferation, migration, invasion, mitochondrial respiration, and aerobic glycolysis. Overexpressing SPAG4 elevated p-PI3K, p-Akt, p-mTOR, and HIF-1α protein levels, which were restored after LY294002 treatment. Furthermore, LY294002 abolished the promotion of SPAG4 overexpression on CRC malignant phenotypes. Collectively, SPAG4 plays an oncogenic role in CRC by promoting mitochondrial respiration and aerobic glycolysis through activating the PI3K/Akt signaling. These findings suggest that inhibition of SPAG4-mediated glucose metabolism may represent a potential strategy for the clinical treatment of CRC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142443479","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}

{"title":"Neurobehavioral and bioaccumulative toxicity in adult in-vivo zebrafish model due to prolonged cadmium exposure in the presence of ketoprofen","authors":"S. Madesh,&nbsp;Gokul Sudhakaran,&nbsp;Ramu Meenatchi,&nbsp;K. Manikandan,&nbsp;Nagarajan Balachandran Dhayanithi,&nbsp;Mikhlid H. Almutairi,&nbsp;Bader O. Almutairi,&nbsp;Ajay Guru,&nbsp;Jesu Arockiaraj","doi":"10.1002/jbt.70005","DOIUrl":"https://doi.org/10.1002/jbt.70005","url":null,"abstract":"<p>Increasing industrial activity causes the release of chemical compounds into aquatic habitats, including toxic heavy metals like cadmium and medications like ketoprofen, posing considerable ecological concerns. Although previous studies have shown that cadmium and ketoprofen individually cause cognitive impairment, there is a lack of information on the combined neurological effects of the two substances. We investigated the neurological consequences of persistent cadmium exposure in the presence of ketoprofen on adult zebrafish, providing an essential model for understanding cumulative impacts on vertebrate organisms. Behavioral assessments, bioaccumulation rates, biochemical studies, and histopathological exams were conducted over 42 days in authentic environmental settings. The results of our study show that cadmium (10 µg/L) and ketoprofen (10 and 100 µg/L) at environmentally relevant concentrations had a significant impact on locomotor activity, social interactions, and cognitive responses, indicating cumulative neurotoxicity in co-exposure groups compared to single pollutant groups. Biochemical tests show disturbances in antioxidant defense systems, while histological examinations reveal structural changes in zebrafish brain regions. Ketoprofen influences cadmium accumulation in the brain, underscoring the importance of conducting complete evaluations to understand the intricate interactions between environmental pollutants. This study improves our understanding of the complex interactions between heavy metals and medications, stressing the need to consider combined exposure when assessing the neurological effects on vertebrate models.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435383","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}

{"title":"RNA methylase RBM15 facilitates malignant progression of colorectal cancer through regulating E2F2 in an m6A modification-dependent manner","authors":"Huijun Zhang,&nbsp;Yuanyuan Li,&nbsp;Ying Zhou,&nbsp;Qihua Xu,&nbsp;Bingling Liao,&nbsp;Xiaofeng Qiu,&nbsp;Jianfeng Liu","doi":"10.1002/jbt.70014","DOIUrl":"https://doi.org/10.1002/jbt.70014","url":null,"abstract":"<p>Recently, RBM15 has emerged as an oncogenic factor in a majority of tumors. However, the mechanism is unclear that accounts for how RBM15-induces colorectal cancer (CRC) progression and it is in need of further study. We determined RBM15 expression through the UALCAN database and RT-qPCR. The role of RBM15 in inducing the malignant and aggressive cancerous phenotype was characterized based on the results of the western blot, RT-qPCR, CCK-8 and transwell assays. The target genes of RBM15 were screened by LinkedOmics. m6A methylation kit was applied to analyze the methylation levels of mRNA. SRAMP website was employed to predict m6A sites of targeted mRNA. RIP, dual luciferase reporter gene and actinomycin D assay were conducted to verify the interactions between RBM15 and its targeted gene, and the presence of m6A modification site of its targeted mRNA, respectively. We confirmed the augmentation of RBM15 expression in CRC, which also has a high clinical diagnostic value for CRC. Functionally, RBM15 silencing clearly restrained malignant cellular processes in CRC cells. Mechanistically, RBM15 bound to E2F2 which increased its m6A binding and stabilized the corresponding E2F2 mRNA formation. Excessive E2F2 largely restored the repression malignant phenotype of tumor cells caused by RBM15 silencing. RBM15 regulated E2F2 in an m6A modification-dependent manner thereby boosting malignant cellular processes in CRC. The RBM15/E2F2 axis may be a novel target for CRC therapy.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435404","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}

{"title":"Monosodium glutamate added to food does not induce damage to the pancreas nor aggravate diabetes due to enhancement of oxidative stress","authors":"Shintaro Yoshida,&nbsp;Huichia Chao,&nbsp;Asuka Takumi,&nbsp;Masanori Kohmura","doi":"10.1002/jbt.23859","DOIUrl":"https://doi.org/10.1002/jbt.23859","url":null,"abstract":"&lt;p&gt;In the article by Gelen, et al. entitled “The investigation of the effects of monosodium glutamate on healthy rat and rats with STZ-induced diabetes,” the authors indicated that oral administration of monosodium glutamate (MSG) at a dose of 30 mg/kg bw/day by gavage for 28 days reduced antioxidative capacity and induced histological abnormalities in the pancreas of healthy rats as well as rats with STZ-induced diabetes. This was attributed to inflammation caused by increased oxidative stress and it was reported that MSG consequently disordered glucose metabolism in healthy rats and aggravated diabetes in STZ-treated rats.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; Finally, it was concluded that not only diabetics, but also healthy people should limit their use of the food additive, MSG. In response to this article, we would like to provide safety information on MSG used as a food additive and comment on these study results.&lt;/p&gt;&lt;p&gt;MSG is one of the most thoroughly studied food additives. It is well established that glutamate added to foods does not enter the blood circulation nor does the blood glutamate concentration rise when MSG is consumed as part of a normal diet, even when consumed at abnormally high levels.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; Glutamate ingested with food is metabolized as an energy source for enterocytes.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;3, 4&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; It has been demonstrated that dietary glutamate is intensively oxidized during the splanchnic first pass in healthy adults and preterm infants.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;5, 6&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; A study that investigated the metabolic fate of dietary glutamate (including MSG) showed that almost all dietary glutamate in the rat gut is metabolized into CO2, lactate, alanine or proline (56%, 13%, 12%, 3% of dietary input, respectively).&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; Rodent and human studies have also shown that the major nutrients in foods, especially metabolizable carbohydrates, effectively attenuate any rise in blood glutamate levels induced by oral administration of MSG.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;8, 9&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; Further studies have shown that the circadian fluctuations in blood glutamate level are not significantly different regardless of whether a diet contains added MSG or not &lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; and that the basal glutamate level is not affected by long-term MSG consumption.&lt;sup&gt;[&lt;/sup&gt;&lt;span&gt;&lt;sup&gt;11&lt;/sup&gt;&lt;/span&gt;&lt;sup&gt;]&lt;/sup&gt; The principal conclusion from these studies is that blood glutamate concentration does not rise when MSG is ingested as part of a normal diet even in cases where intake is abnormally high. Considering the results of these studies on the safety of MSG, international scientific committees and regulatory agencies have stated that MSG is safe as a food additive. Since 1958, MSG has been classified by the US Food and Drug Administration as “generally recognized as safe.” ","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.23859","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435467","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":"Gastrointestinal toxicity following sub-acute exposure of erythrosine in rats: biochemical, oxidative stress, DNA damage and histopathological studies","authors":"Mandeep Singh,&nbsp;Pooja Chadha","doi":"10.1002/jbt.70007","DOIUrl":"https://doi.org/10.1002/jbt.70007","url":null,"abstract":"<p>Erythrosine, a synthetic food dye, has been controversial due to its potential health risks. This study examines the effect of erythrosine on activity of antioxidative enzymes, oxidative stress indices, DNA damage through comet assay, and histopathological changes on stomach, intestine, and colon over a period of 28 days in rats. Twenty-four rats were randomly divided into four groups (<i>n</i> = 6). The first is the control group and then one each for three doses of erythrosine based on acceptable daily intake (¼ ADI, ½ ADI, and ADI, 0.1 mg/kg body weight). The results revealed that with increasing dosages the activity of catalase decreased in stomach and intestine but in colon, the catalase activity increased. Superoxide dismutase and glutathione-S-transferase activity decreased in dose-dependent manner in all three tissues. While, in stomach and intestine, the acetylcholinesterase activity showed increment in ¼ ADI dose group and then declined in ½ ADI and ADI dose-administered rats. The oxidative stress indicators showed elevated levels of lipid peroxidation, hydrogen peroxide concentration, and lactate dehydrogenase activity suggesting heightened free radical activity and potential oxidative damage. The comet test was used to evaluate DNA damage, revealing substantial damage in the erythrosine administered groups. Histopathological examination showed inflammatory infiltration and other degenerative changes in gastrointestinal tract, highlighting the dye's adverse effects. The research underscores the need for a comprehensive reevaluation of the safety and toxicity of food dyes like erythrosine, especially considering the inconsistencies in existing studies regarding the dye's safety.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435581","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}

{"title":"miR-148a-3p mitigation of coronary artery disease through PCSK9/NF-κB inhibition of vascular endothelial cell injury","authors":"Jiong Tang,&nbsp;Menghuai Ma,&nbsp;Fan Liu,&nbsp;Xiaomei Yin,&nbsp;Haotian Shi,&nbsp;Qing Li,&nbsp;Kai Yang,&nbsp;Mengyue Yu","doi":"10.1002/jbt.70011","DOIUrl":"https://doi.org/10.1002/jbt.70011","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Coronary artery disease (CAD) causes myocardial ischemia, narrowing or occlusion of the lumen. Although great progress has been made in the treatment of CAD, the existing treatment methods do not meet the clinical needs, so it is urgent to find new treatment methods. The aim of this study was to investigate the mechanism of action of miR-148a-3p in alleviating CAD by inhibiting vascular endothelial cell injury and to provide new ideas for the treatment of CAD. A cell model was constructed by lipopolysaccharide (LPS) induction of vascular endothelial cells, and a CAD rat model was established by a high-fat diet and intraperitoneal injection of posterior pituitary hormone. Relevant indices were detected by RT-qPCR, ELISA, Western blot, MTT, and flow cytometry. The results indicate that in LPS-induced vascular endothelial cell assays, miR-148a-3p inhibited the upregulation of PCSK9, thereby suppressing the NF-κB signaling pathway and promoting vascular endothelial cell proliferation. Overexpression of PCSK9 and the addition of NF-κB signaling pathway activator increased vascular endothelial cell apoptosis. In animal experiments, miR-148a-3p alleviated the symptoms of CAD rats, whereas overexpression of PCSK9 promoted apoptosis and increased atheromatous plaque area in CAD rats. In conclusion, miR-148a-3p inhibits the NF-κB signaling pathway through downregulation of PCSK9, thereby protecting vascular endothelial cells and alleviating CAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435582","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}

{"title":"AGK2, a SIRT2 inhibitor, ameliorates D-galactose-induced liver fibrosis by inhibiting fibrogenic factors","authors":"Aslı Nur Bahar,&nbsp;Arzu Keskin-Aktan,&nbsp;Saadet Özen Akarca-Dizakar,&nbsp;Gizem Sonugür,&nbsp;Kazime Gonca Akbulut","doi":"10.1002/jbt.70000","DOIUrl":"https://doi.org/10.1002/jbt.70000","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>In our study, we aimed to investigate the effect of SIRT2 inhibition on function, fibrosis and inflammation in liver fibrosis induced by <span>D</span>-Galactose (D-Gal) administration. A total of 32 3-month-old Sprague Dawley rats were used in the study. Rats were divided into 4 groups as Control, <span>d</span>-Gal, Solvent+<span>d</span>-Gal, <span>d</span>-Gal+AGK2+Solvent. <span>d</span>-Gal (150 mg/kg/day), AGK-2 (10 µM/bw) as a specific SIRT2 inhibitor, 4%DMSO + PBS as a solvent was applied to the experimental groups and physiological saline was applied to the control group for 10 weeks. All applications were performed subcutaneously. Histological fibrotic changes were studied in the liver tissues by Masson's trichrome staining, hematoxylin and eosin staining and immunohistochemistry and the levels of selected factors were determined by quantitative reverse transcription-polymerase chain reaction, western blot analysis, and immunohistochemical analysis. Biochemical parameters and Paraoxonase levels were determined in the plasma. <span>d</span>-Galactose administration increased AST, AST-ALT Ratio, APRI, SIRT2 protein expression, IL1β, TGF β, β-catenin, Type I collagen, Type III collagen and α-SMA, collagen fiber density and histopathological score. ALT and lipid panels were not changed and paraxonase plasma level was shown to decrease. These effects were largely blocked by the SIRT2 inhibitor AGK2. These findings suggest that SIRT2 inhibition attenuates <span>d</span>-Gal-induced liver injury and that this protection may be due to its antifibrotic and anti-inflammatory activities.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435580","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":"Therapeutic overview of sudachitin","authors":"Ahsas Goyal,&nbsp;Om Sikarwar,&nbsp;Aanchal Verma,&nbsp;Kunal Solanki,&nbsp;Manoj Kumar Mishra","doi":"10.1002/jbt.70003","DOIUrl":"10.1002/jbt.70003","url":null,"abstract":"<p>Citrus fruits are extensively cultivated and eaten both raw and in refined forms. Citrus fruit peels are highly concentrated in polyphenolic substances. This makes them useful resources. Polymethoxyflavones (PMFs), found in citrus peels, belong to a specific subclass of flavonoids where most or all hydroxyl groups are methylated. PMFs have been documented to possess chemopreventive actions, anticancer, anti-inflammatory, and anti-atherosclerosis properties, as well as neuroprotective effects. Sudachitin, a PMF, is primarily found in Citrus sudachi. Japan's Tokushima prefecture is home to this famous fruit. In recent years, there has been a growing interest among researchers in exploring the potential health benefits of sudachitin, spurred by its presence in traditional diets and its association with various positive health outcomes. Studies conducted over the past decade have revealed promising effects of sudachitin in multiple health conditions, including cancer, skin disorders, inflammatory conditions, diabetes, obesity, and neurodegenerative disorders. Although these promising results exist, there is still a need for thorough preclinical and clinical research to confirm sudachitin's effectiveness in treating chronic conditions. This review seeks to summarize animal and cell studies exploring sudachitin's pharmacological properties and the potential molecular pathways underlying its therapeutic effects. Through this, we aim to clarify the clinical potential of sudachitin across various disorders, paving the way for future research and the development of sudachitin-based therapies.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"38 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400369","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}