Toxicology ResearchPub Date : 2025-08-28eCollection Date: 2025-08-01DOI: 10.1093/toxres/tfaf122
Jingyi Shi, Shaoke Hou, Xinyu Yao
{"title":"MiR-1291 mediates the protective effect of sevoflurane preconditioning against hypoxia/reoxygenation-induced myocardial cell injury.","authors":"Jingyi Shi, Shaoke Hou, Xinyu Yao","doi":"10.1093/toxres/tfaf122","DOIUrl":"https://doi.org/10.1093/toxres/tfaf122","url":null,"abstract":"<p><p>The protective effects of sevoflurane (Sev) in cardiovascular disease have been well documented in studies. The investigation aimed to clarify the contribution of miR-1291 to the pathophysiological process of hypoxia-reoxygenation (H/R)-induced cardiomyocyte injury in the setting of Sev preconditioning. H/R cell models were constructed with AC16 cells and the cell models were pretreated with 1%, 1.5% and 2% concentrations of Sev. Quantitative reverse transcription polymerase chain reaction was performed to detect miR-1291 and NF2 expression in cells. Cell viability was assessed using the cell counting kit-8 assay. Apoptosis was evaluated via flow cytometry. Cellular cardiac troponin I (cTnI), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immunosorbent assay. Dual luciferase reporter gene assay and RIP analysis were applied to validate the binding of miR-1291 to NF2. In the H/R cell model, miR-1291 was downregulated, and this was accompanied by reduced cell viability, increased apoptosis, and elevated levels of cTnI, LDH, IL-6 and TNF-α. In contrast, inhibition of miR-1291 expression impaired the protective effect of Sev on cardiomyocytes. NF2 was a downstream target gene of miR-1291, and miR-1291 negatively regulated the expression of NF2. Knockdown of NF2 expression alleviated the effects of miR-1291 inhibition on Sev-treated cells. Sev attenuates H/R-induced cardiomyocyte injury by regulating miR-1291/NF2 expression and inhibiting apoptosis and inflammatory responses. This study unveils a novel mechanism of Sev-mediated myocardial protection, offering theoretical support and potential therapeutic targets for myocardial injury prevention and treatment.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf122"},"PeriodicalIF":2.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicology ResearchPub Date : 2025-08-28eCollection Date: 2025-08-01DOI: 10.1093/toxres/tfaf130
Mualla Pınar Elci, Sema Ören, Ece Miser-Salihoglu, Sevgi Yardim-Akaydin
{"title":"Examination of the effects of polyunsaturated fatty acids on the alzheimer model caused by amiloid β<sub>1-42</sub> toxicity in human SHSY5Y cells by in vitro methods.","authors":"Mualla Pınar Elci, Sema Ören, Ece Miser-Salihoglu, Sevgi Yardim-Akaydin","doi":"10.1093/toxres/tfaf130","DOIUrl":"10.1093/toxres/tfaf130","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive, chronic disease characterized by impaired cognitive function. Currently, there is no complete cure for ad; current treatments are aimed at reducing symptoms and slowing the progression of the disease. It is thought that the amount of fatty acid consumption and the balance between them may be protective against neurological diseases. In this study, it was aimed to determine the protective effects of Ω3/Ω6 polyunsaturated fatty acids ratios in Aβ<sub>1-42</sub>-induced ad model in human neuroblastoma (SH-SY5Y) cells. The viability of cells was determined by MTT assay. The percentage of apoptotic cells was determined by FITC-conjugated Annexin-V/PI. ROS, MMP and cell cycle analysis were performed by flow cytometry. The amount of acetylcholinesterase enzyme was measured with a commercial kit. 48 h after the application, a statistically significant decrease was observed in the MTT test in the 1/1, 1/2 and 1/8 groups and in the amount of AChE in the 1/4, 1/8 and 1/16 groups. According to apoptosis findings, all ratios were observed to reduce cell viability compared to the control group. ROS and MMP levels were detected to decrease in all groups compared to the control group. The highest neuroprotective effect against oxidative stress was observed at 1/1 dose. Aβ<sub>1-42</sub> induced blockade of the cell cycle was observed to be partially corrected by 1/8 dose. As a result, it can be said that Ω6 and Ω3 fatty acids, when used in 1/4 and 1/8 doses can provide a protective effect against Alzheimer's disease.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf130"},"PeriodicalIF":2.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicology ResearchPub Date : 2025-08-27eCollection Date: 2025-08-01DOI: 10.1093/toxres/tfaf131
Mona N Hussein, Khalid S Alotaibi, Saed A Althobaiti, Shatha B Albattal, Xiao Ke, Jinxia Dai, Gang Cao, Mohamed Mohamed Soliman
{"title":"LPS mediated neuronal c-Fos activation: whole-brain mapping, site and time effect in intoxicated mice.","authors":"Mona N Hussein, Khalid S Alotaibi, Saed A Althobaiti, Shatha B Albattal, Xiao Ke, Jinxia Dai, Gang Cao, Mohamed Mohamed Soliman","doi":"10.1093/toxres/tfaf131","DOIUrl":"https://doi.org/10.1093/toxres/tfaf131","url":null,"abstract":"<p><p>Lipopolysaccharide (LPS; a bacterial endotoxin) treatment causes acute inflammatory conditions. Acute inflammation causes the brain to activate neurons in some brain nuclei known as circumventricular organs. The c-Fos immunoreaction could be used to assess this neural activity. The current study aimed to check the activated neurons in time and site effect during toxicity and inflammation induced by LPS. The c-Fos antibody immunofluorescence labeling was checked at one, three, and six hours after LPS intoxication. Moreover, a retrograde viral tracing approach was employed to verify the neuronal connections among certain brain nuclei that were activated. The results indicated the activation of several brain nuclei in the hippocampus, epithalamus, thalamus, hypothalamus, basal ganglia, midbrain, and medulla oblongata. The type of brain nuclei and the number of neurons that were activated in relation to the duration of acute inflammation were clearly different. Furthermore, this research demonstrated that these active brain nuclei were connected neuronally. Ultimately, acute inflammatory responses induced by LPS treatment activated dorsal raphe serotonergic neurons. Twenty-two brain nuclei were shown to be involved in the neuroinflammatory response via whole-brain mapping. One hour after LPS administration, neurons in the dorsomedial hypothalamic nucleus (DM), lateral septal nucleus (LS), and solitary tract nucleus (SOL) were significantly activated. However, the sensory circumventricular organs (CVOs) were activated three hours after LPS treatment. It was also demonstrated that dorsal raphe serotonergic neurons play a vital role in the body's reaction to acute inflammation. This study confirmed the involvement of dorsal raphe serotonergic neurons in response to acute inflammation and toxicity induced by LPS.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf131"},"PeriodicalIF":2.1,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicology ResearchPub Date : 2025-08-22eCollection Date: 2025-08-01DOI: 10.1093/toxres/tfaf118
Aline Mocellin Conte, Fernanda Mocellin Conte, Larissa V Cestonaro, Maria Fernanda Nunes Ribeiro, Rodrigo F da Silva, Renata De Faveri, Larissa Benvenutti, Solange C Garcia, José Roberto Santin, Rodrigo Ligabue-Braun, Bruno Dutra Arbo, Marcelo Dutra Arbo
{"title":"Flumetralin based plant growth regulator used in tobacco cultivation induces immune and cytotoxicity in vitro.","authors":"Aline Mocellin Conte, Fernanda Mocellin Conte, Larissa V Cestonaro, Maria Fernanda Nunes Ribeiro, Rodrigo F da Silva, Renata De Faveri, Larissa Benvenutti, Solange C Garcia, José Roberto Santin, Rodrigo Ligabue-Braun, Bruno Dutra Arbo, Marcelo Dutra Arbo","doi":"10.1093/toxres/tfaf118","DOIUrl":"https://doi.org/10.1093/toxres/tfaf118","url":null,"abstract":"<p><p>Tobacco production lasts about 10 months and various pesticides are used, including growth inhibitors, which flumetralin is the most used. This is an herbicide that acts as a synthetic and plant growth regulator. Therefore, this work aimed to evaluate the toxicity of the growth regulator flumetralin in RAW 264.7 and 3T3 cell lines. Cytotoxicity was assessed by MTT reduction and neutral red uptake assays after 24 h of incubation with flumetralin. Mitochondrial integrity, production of reactive species and cytokine profile were evaluated in both cell lines. Furthermore, NO production was evaluated in RAW 264.7 cells, while comet assay was evaluated in 3T3 cells. An increase in reactive species production was observed in both cell lines. In RAW 264.7 cells were observed an increase in mitochondrial membrane potential, while 3T3 cells presented a mitochondrial depolarization. At all tested concentrations, flumetralin increased TNF-α levels and decreased IL-10 levels in RAW 264.7, and increased TNF and IL-1ß in 3T3 cells. In addition, at all tested concentrations, flumetralin induced DNA damage in 3T3 cells. It was possible to observe the cytotoxic effect of flumetralin on the tested cell lines, as well as a possible generation of an inflammatory response and immune deregulation.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf118"},"PeriodicalIF":2.1,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicology ResearchPub Date : 2025-08-20eCollection Date: 2025-08-01DOI: 10.1093/toxres/tfaf127
Aditya Shukla, Srimonti Sarkar, Alok Kumar Sil
{"title":"Cigarette smoke impairs the endocytotic process in <i>Saccharomyces cerevisiae</i>.","authors":"Aditya Shukla, Srimonti Sarkar, Alok Kumar Sil","doi":"10.1093/toxres/tfaf127","DOIUrl":"10.1093/toxres/tfaf127","url":null,"abstract":"<p><p>The accumulation of misfolded proteins inside the cells has been considered to be an important contributor to the development of cigarette smoke-mediated diseases. Since endocytosis plays a crucial role in protein trafficking and clearance, impaired endocytosis may contribute to cigarette smoke-mediated protein accumulation. Therefore, the current study investigated the effects of cigarette smoke extract (CSE) on the endocytosis process in the yeast <i>Saccharomyces cerevisiae</i>. The current study demonstrated that treatment of cells with CSE resulted in reduced uptake of the FM4-64 stain, indicating impaired endocytosis. Further analysis revealed that CSE treatment resulted in a defect in the recruitment of proteins involved in endocytosis. Also, aberrant actin filament morphology was found upon CSE treatment, which might interfere with vesicle budding from the membrane. Moreover, the current study showed that the PI(4,5)P2 level in the plasma membrane in CSE-treated cells is reduced due to the failed translocation of MSS4 kinase to the membrane. This reduced PI(4,5)P2 results in aberrant actin filament morphology. Thus, the current study demonstrates that CSE treatment causes endocytosis defects and provides insight into this defective process.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf127"},"PeriodicalIF":2.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicology ResearchPub Date : 2025-08-18eCollection Date: 2025-08-01DOI: 10.1093/toxres/tfaf120
Soontag Jung, Yixian Quah, Onju Ham, Sangyun Kim, Ji-Seong Jeong, Woojin Kim, Seung-Jin Lee, Wook-Joon Yu
{"title":"Integrated transcriptome analysis of rats exposed to bisphenol mixtures from the fetal to developmental stage.","authors":"Soontag Jung, Yixian Quah, Onju Ham, Sangyun Kim, Ji-Seong Jeong, Woojin Kim, Seung-Jin Lee, Wook-Joon Yu","doi":"10.1093/toxres/tfaf120","DOIUrl":"10.1093/toxres/tfaf120","url":null,"abstract":"<p><p>Bisphenol A (BPA), widely used in plastics and resins, has raised health concerns for its endocrine-disrupting effects. BPA analogues such as bisphenol S (BPS) and bisphenol F (BPF) emerged as alternatives but exhibit similar risks. Despite regulations on BPA in many countries, alternatives remain insufficiently controlled. Although the safety of BPS and BPF has not been sufficiently verified, these compounds have already been detected in various environmental sources and human urine, raising serious concerns. While bisphenols are expected to have various adverse effects, research remains limited. This study investigates the adverse effects of bisphenols mixture on rats from fetal stage to young adulthood by analyzing transcriptomes in multiple tissues-liver, kidney, thyroid gland, and reproductive organs-and by gender, to identify key genes affected by bisphenol exposure. Dams were orally administered test substances from gestational day 6 to lactation day 6, and F1 pups received the same substances at half the concentration from postnatal day 7 to day 63. Transcriptome analysis of the collected tissues identified core genes related to high-density lipoprotein metabolism and hormone secretion, providing insights into mechanisms through which BPA may disrupt hormonal balance. Furthermore, the study suggests that combined exposure to BPA, BPS, and BPF produces distinct effects compared to BPA alone, with pronounced impacts on the thyroid and reproductive organs, despite individual concentrations being below the no-observed-adverse-effect-level. These findings highlight the potential cumulative impact of endocrine disrupting chemicals in the body.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf120"},"PeriodicalIF":2.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12360700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The association of organophosphate flame retardants (OPFRs) exposure on omega-3 fatty acids metabolism: evidence derived from the United States general population.","authors":"Ting-Hsuan Hsu, Hsiu-Yung Pan, Kai-Fan Tsai, Chia-Te Kung, Wan-Ting Huang, Huey-Ling You, Shau-Hsuan Li, Chin-Chou Wang, Wen-Chin Lee, Fu-Jen Cheng","doi":"10.1093/toxres/tfaf119","DOIUrl":"10.1093/toxres/tfaf119","url":null,"abstract":"<p><p>This study investigated the association between exposure to organophosphate flame retardants (OPFRs) and serum omega-3 fatty acid levels in the general U.S. population, using data from 1,350 adults in the 2011-2014 National Health and Nutrition Examination Survey (NHANES). OPFRs are widely used in consumer and industrial products, and emerging evidence has linked them to disruptions in lipid metabolism. In this study, urinary concentrations of five OPFR metabolites were analyzed in relation to serum levels of key omega-3 fatty acids, including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and docosapentaenoic acid (DPA), with adjustment for potential confounders. We observed significant negative associations between higher levels of diphenyl phosphate (DPhP) and the concentrations of EPA, DHA, and DPA. Similarly, bis(1,3-dichloro-2-propyl) phosphate (BDCPP) was negatively associated with EPA, bis(1-chloro-2-propyl) phosphate (BCEP) with DHA, and dibutyl phosphate (DBUP) with alpha-linolenic acid and DPA. Participants in the highest quartiles of DPhP and BDCPP exposure showed 18.2 and 18.4% lower EPA levels compared to the lowest quartiles, respectively. DHA levels declined by 17.5% with increasing DPhP and by 9.4% with sum of OPFRs (ΣOPFRs). These findings suggest that environmental OPFR exposure may interfere with omega-3 fatty acid metabolism and highlight potential metabolic and cardiovascular risks associated with these widely used flame retardants. These results underscore the importance of continued environmental monitoring and research into the health effects of OPFRs, particularly as their global use and human exposure continue to rise.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf119"},"PeriodicalIF":2.1,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unveiling the protective efficacy of rutin against High-Sucrose Diet-induced oxidative stress, biochemical alterations, and organismal hazards in <i>Drosophila melanogaster</i>.","authors":"Abhratanu Ganguly, Kanchana Das, Sayantani Nanda, Moutushi Mandi, Gopal Biswas, Siddhartha Ghanty, Prem Rajak","doi":"10.1093/toxres/tfaf121","DOIUrl":"10.1093/toxres/tfaf121","url":null,"abstract":"<p><p>Sucrose is a common ingredient in many foods. However, intake of High-Sucrose Diet (HSD) for a longer duration can fuel metabolic and physiological issues. Hence, continuous efforts implying animal models are essential to mitigate the adverse impacts of HSD on health. Rutin is a bioactive compound with greater biocompatibility and health-promoting effects. Nonetheless, studies investigating the protective efficacy of rutin against HSD-induced health hazards are scarce. Hence, the present work aims to explore the ameliorative potential of rutin against the HSD-mediated hazards in <i>Drosophila melanogaster</i>. First instar larvae of <i>D. melanogaster</i> were orally exposed to control, HSD (30%-sucrose), and rutin-supplemented foods. <i>D. melanogaster</i> exposed to HSD for prolonged periods exhibited reduced survivability, physical fitness, and growth, while rutin co-supplementation significantly mitigated these effects. Rutin co-treatment also normalized HSD-induced eye morphology defects and light insensitivity, alleviated oxidative stress, and normalized sub-cellular endogenous antioxidants. Moreover, rutin supplementation improved cell survivability in visceral organs, reduced protein and lipid oxidation as evidenced by down-regulated protein carbonyl and MDA contents, and boosted CYP4501A1 and GST functions. Thus, co-administration of rutin, mainly at 150, 200, and 250 μM concentrations, effectively mitigated HSD-induced oxidative stress and associated organismal and sub-organismal level adverse outcomes in <i>D. melanogaster</i>, suggesting a protective dietary intervention of rutin against HSD-induced organismal and sub-organismal-level health hazards. Moreover, rutin can be considered as a promising bioactive compound in diets for artificial insect rearing in a controlled environment.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf121"},"PeriodicalIF":2.1,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicology ResearchPub Date : 2025-08-16eCollection Date: 2025-08-01DOI: 10.1093/toxres/tfaf124
Taiqiang Jiao, Ling Yuan, Jiaqing Li, Bo Zhou, Xiangyang Li, Yifan Yang, Wenjie Jiang, Yang Niu, Yi Nan
{"title":"Subacute oral toxicity study of maxing Kugan decoction on rats.","authors":"Taiqiang Jiao, Ling Yuan, Jiaqing Li, Bo Zhou, Xiangyang Li, Yifan Yang, Wenjie Jiang, Yang Niu, Yi Nan","doi":"10.1093/toxres/tfaf124","DOIUrl":"10.1093/toxres/tfaf124","url":null,"abstract":"<p><p>The Maxing Kugan Decoction (MKD) is a traditional Chinese medicine prescription specifically designed for respiratory infectious diseases in the northwest region, particularly targeting influenza during the winter and spring seasons. While its clinical efficacy has been established, there is a significant gap in its toxicological safety. This study aims to evaluate the subacute oral toxicity of MKD in rats, focusing on its effects on food consumption, weight, vital signs, haematological parameters, and organ histology. To determine subacute oral toxicity, MKD was administered by gavage at 12.6, 25.2, or 50.4 g/kg/day to male and female rats for 90 days. Meanwhile, the general behavior, body weight, food intake, urine routine parameters, blood biochemical, hematological parameters, coagulation parameters, organ coefficients and organ histopathology were recorded and analyzed. The results showed that experimental rats were healthy and displayed no evidence of toxicity. Furthermore, no mortality or abnormalities in general conditions, including diet and weight, were noted. While the levels of a few indicators changed during administration, their levels remained within the normal range and were not correlated with dose or gender. Overall, no toxicological significance was recorded. Meanwhile, histopathological analysis did not identify abnormal pathological changes in tissue structure and cell morphology across organs, and no significant delayed toxic reactions were detected during the remission period. Overall, our results indicated that oral administration of 50.4 g/kg (60 times the clinical dose in humans) of MKD for three months is safe for SD rats and is not associated with toxic side effects.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf124"},"PeriodicalIF":2.1,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357491/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Toxicology ResearchPub Date : 2025-08-16eCollection Date: 2025-08-01DOI: 10.1093/toxres/tfaf125
Sharang Gupta
{"title":"Response to \"Comparative in vitro and in silico evaluation of the toxic effects of metformin and/or ascorbic acid, new treatment options in the treatment of Melasma\".","authors":"Sharang Gupta","doi":"10.1093/toxres/tfaf125","DOIUrl":"10.1093/toxres/tfaf125","url":null,"abstract":"","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf125"},"PeriodicalIF":2.1,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}