Ji-Young Kim, Geun-Seup Shin, Mi-Jin An, Hyun-Min Lee, Ah-Ra Jo, Yuna Park, Jinho Kim, Yujeong Hwangbo, Chul-Hong Kim, Jung-Woong Kim
{"title":"Comparative study of cytotoxic Signaling pathways in H1299 cells exposed to alternative Bisphenols: BPA, BPF, and BPS.","authors":"Ji-Young Kim, Geun-Seup Shin, Mi-Jin An, Hyun-Min Lee, Ah-Ra Jo, Yuna Park, Jinho Kim, Yujeong Hwangbo, Chul-Hong Kim, Jung-Woong Kim","doi":"10.1093/toxres/tfae200","DOIUrl":"10.1093/toxres/tfae200","url":null,"abstract":"<p><strong>Background: </strong>Bisphenols are prevalent in food, plastics, consumer goods, and industrial products. Bisphenol A (BPA) and its substitutes, bisphenol F (BPF) and bisphenol S (BPS), are known to act as estrogen mimics, leading to reproductive disorders, disruptions in fat metabolism, and abnormalities in brain development.</p><p><strong>Objectives: </strong>Despite numerous studies exploring the adverse effects of bisphenols both <i>in vitro</i> and <i>in vivo</i>, the molecular mechanisms by which these compounds affect lung cells remain poorly understood. This study aims to compare the effects of BPA, BPF, and BPS on the physiological behavior of human nonsmall cell lung cancer (NSCLC) cells.</p><p><strong>Materials and methods: </strong>Human non-small cell lung cancer (NSCLC) H1299 cells were treated with various concentration of BPA, BPF and BPS during different exposure time. Cellular physiology for viability and cell cycle was assessed by the staining with apoptotic cell makers such as active Caspase-3 and cyclins antibodies. Toxicological effect was quantitatively counted by using flow-cytometry analysis.</p><p><strong>Results: </strong>Our findings indicate that BPA induces apoptosis by increasing active Caspase-3 levels in H1299 cells, whereas BPF and BPS do not promote late apoptosis. Additionally, BPA was found to upregulate cyclin B1, causing cell cycle arrest at the G0/G1 phase and leading to apoptotic cell death through Caspase-3 activation. Conclusion: These results demonstrate that BPA, BPF, and BPS differentially impact cell viability, cell cycle progression, and cell death in human NSCLC cells.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae200"},"PeriodicalIF":2.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826759","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 : 2024-11-27eCollection Date: 2024-12-01DOI: 10.1093/toxres/tfae203
Heba Mohamed Abdou, Alaa Mohamed Saad, Heba-Tallah Abd Elrahim Abd Elkader, Amina E Essawy
{"title":"Role of vitamin D<sub>3</sub> in mitigating sodium arsenite-induced neurotoxicity in male rats.","authors":"Heba Mohamed Abdou, Alaa Mohamed Saad, Heba-Tallah Abd Elrahim Abd Elkader, Amina E Essawy","doi":"10.1093/toxres/tfae203","DOIUrl":"10.1093/toxres/tfae203","url":null,"abstract":"<p><p>Arsenic is associated with various neurological disorders, notably affecting memory and cognitive functions. The current study examined the protective effects of vitamin D<sub>3</sub> (Vit. D<sub>3</sub>) in countering oxidative stress, neuroinflammation and apoptosis induced by sodium arsenite (SA) in the cerebral cortex of rats. Male Wistar rats were subjected to a daily oral administration of sodium arsenite (NaAsO<sub>2</sub>, SA) at a dosage of 5 mg/kg, along with 500 IU/kg of Vit. D<sub>3</sub>, and a combination of both substances for four weeks. The results indicated that Vit. D<sub>3</sub> effectively mitigated the SA-induced increase in oxidative stress markers, thiobarbituric acid reactive substances (TBARS) and nitric oxide (NO), the decrease in antioxidants (reduced glutathione; GSH, superoxide dismutase; SOD, catalase; CAT, and glutathione peroxidase; GPx), as well as the increase in pro-inflammatory markers including, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and amyloid-beta (Aβ)1-42. Furthermore, Vit. D<sub>3</sub> reversed the alterations in the neurochemicals acetylcholinesterase (AchE), monoamine oxidase (MAO), dopamine (DA), and acetylcholine (Ach) and ameliorated the histopathological changes in the cerebral cortex. Moreover, immunohistochemical analyses revealed that Vit. D<sub>3</sub> reduced the SA-induced overexpression of cerebral cysteine aspartate-specific protease-3 (caspase-3) and glial fibrillary acidic protein (GFAP) in the cerebral cortex of male rats. Consequently, the co-administration of Vit. D<sub>3</sub> can protect the cerebral cortex against SA-induced neurotoxicity, primarily through its antioxidant, anti-inflammatory, anti-apoptotic, and anti-astrogliosis effects.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae203"},"PeriodicalIF":2.2,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11602150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749453","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 : 2024-11-11eCollection Date: 2024-12-01DOI: 10.1093/toxres/tfae182
Sohel S Shaikh, Snehal Patel, Anis Malik, Aakash Kumar S
{"title":"Efficacy and safety assessment of probiotic <i>Bacillus coagulans (Heyndrickxia coagulans)</i> BCP92 for treatment of diarrhea.","authors":"Sohel S Shaikh, Snehal Patel, Anis Malik, Aakash Kumar S","doi":"10.1093/toxres/tfae182","DOIUrl":"10.1093/toxres/tfae182","url":null,"abstract":"<p><strong>Objective: </strong>Probiotics offer a potentially new therapeutic approach for the treatment of diarrhea. This study aimed to determine the anti-diarrheal activity of <i>Bacillus coagulans</i> BCP92 (MTCC 25460) and its safety assessment (acute and sub-acute toxicity studies) in animal models and cell lines.</p><p><strong>Methods: </strong>The antidiarrheal activity was studied in mice using a castor oil-induced diarrhea model. In the acute toxicity study, the rats were orally fed 2000 mg/kg (4 × 1011 CFU/g) of <i>B. coagulans</i> BCP92 (MTCC 25460) as a single dose, and for sub-acute toxicity study rats received 250, 500, and 1,000 mg/kg/day for 28 days. At the end of the treatment, body weight, organ weight, food intake, biochemical parameters, hematological parameters, and histopathology were studied. <i>B. coagulans</i> BCP92 is effective against diarrhea by reducing the onset of diarrhea (latency), frequency of defecation, total fecal weight, and percentage of defecation. In-vitro MTT assay was performed on Vero cell lines.</p><p><strong>Results: </strong>In-vitro MTT assay showed a cytoprotective effect. In acute toxicity study, 2000 mg/kg dose did not cause any alteration in clinical signs, morbidity, or mortality. The findings of the subacute toxicity study showed no alterations in physical appearance and behavioral patterns. Moreover, no significant variations were found in organ weights and hematological and biochemical parameters of the treated groups in the control group. Furthermore, no visible histological changes were observed in the heart, lung, liver, and kidney of the high-dose treatment groups.</p><p><strong>Conclusion: </strong>Thus, the results of the present study conclude that <i>B. coagulans</i> BCP92 is safe for human use in the treatment of diarrhea.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 6","pages":"tfae182"},"PeriodicalIF":2.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142612887","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":"Potential protective role of chlorogenic acid against cyclophosphamide-induced reproductive damage in male mice.","authors":"Hong-Xing Zheng, You-Mei Xu, Shu-Cong Fan, Shan-Shan Qi, Fan-Fan Jia, Wei Wu, Chen Chen","doi":"10.1093/toxres/tfae176","DOIUrl":"10.1093/toxres/tfae176","url":null,"abstract":"<p><strong>Background: </strong>Cyclophosphamide (CP) is an anticancer drug; however, clinical utilization of CP is limited, resulting from its considerable toxicities. This research was performed to explore the protective effects of Chlorogenic acid (CGA) on reproductive damage induced by CP in mice.</p><p><strong>Methods: </strong>Blood samples were collected for analysis of hormone content subsequently; semen samples were evaluated for quality, and testis samples were used for histopathological evaluation and analysis of oxidative stress biomarkers, protein and gene expression levels of steroid regulatory factors, and steroid synthase.</p><p><strong>Results: </strong>The results noted that CGA increased serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) activity; increased SOD, GPx, and GSH oxidative stress levels in testis tissue; and decreased MDA content in testis tissue. Testicular cells in the CGA treatment group gradually returned to normal morphology, and CYP11A1 and CYP17A1 levels increased after CGA treatment. The mRNA levels of CYP11A1, CYP17A1, StAR, 3β-HSD, and 17β-HSD were significantly raised in the CGA dose group. In the test dose range, CGA can improve sperm quality, quantitative abnormality, and serum T synthesis disorder caused by CP. This mechanism may be correlated with the inhibition of oxidative stress and antioxidation levels.</p><p><strong>Conclusions: </strong>Therefore, CGA has a protective impact on testicular injuries arising from CP in mice.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae176"},"PeriodicalIF":2.2,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519035/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542970","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 : 2024-10-27eCollection Date: 2024-10-01DOI: 10.1093/toxres/tfae178
Christopher J Waine, Peter Watts, James Hopkins
{"title":"The cliff-edge of toxicological concern: highlighting the potential issues of an over-reliance on \"less-than-lifetime\" thresholds.","authors":"Christopher J Waine, Peter Watts, James Hopkins","doi":"10.1093/toxres/tfae178","DOIUrl":"https://doi.org/10.1093/toxres/tfae178","url":null,"abstract":"<p><p>The Threshold of Toxicological Concern (TTC) is a very well-established concept in applied toxicology, and has become a key tool for the pragmatic human health risk assessment of data-poor chemicals. Within the pharmaceutical sector, regulatory guidance on genotoxins defaults to a TTC of 1.5 μg/day equating to a maximum lifetime cancer risk of 1 in 100,000. Higher doses for drug products where exposures are intermittent or otherwise \"less-than-lifetime\" (LTL) are also considered tolerable. This also allows substance-specific lifetime Acceptable Intakes (AIs) for known genotoxic carcinogens to be scaled up for shorter durations. The default TTCs for assessing LTL exposures build in conservatism such that there is deviation from strict linearity. However, close to the boundaries between LTL categories there can be such a difference in the default tolerable intakes that a health risk assessment can yield conflicting results. We have presented a theoretical case study based on our recent work that illustrates this apparent \"cliff-edge.\" The total acceptable cumulative dose over a 56-day treatment is - in absolute terms - one third of that allowed over 28 days, despite the maximum cancer risk of the longer exposure being an order of magnitude higher. Our analysis suggests the need for careful consideration of what might represent tolerable exposures in the region of the category limits, rather than simply adopting the hardline default. Where a potential patient exposure is found to be above a default value, there is real value in refining the cancer risk estimates using the Lifetime Cumulative Dose approach.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae178"},"PeriodicalIF":2.2,"publicationDate":"2024-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542971","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":"Effects of Immunotoxicity biomarkers, essential elements and vitamin D levels on the severity levels of COVID-19 disease in Turkey.","authors":"Jülide Secerlı, Serdar Çetinkaya, İlknur Sıla Leblebici, Latif Alperen Özdemir, Çiğdem Yücel, Eda Karaismailoğlu, Umut Kara, Aydan Özcan, Nesrin Öcal, Yakup Arslan, Serkan Şenkal, Onur Erdem, Merve Güdül Bacanlı","doi":"10.1093/toxres/tfae177","DOIUrl":"https://doi.org/10.1093/toxres/tfae177","url":null,"abstract":"<p><p>Many mechanisms are thought to play a role in the pathogenesis of the COVID-19 pandemic, which started in 2019 and affected the whole world. It has been claimed that a deficiency in the immune system can significantly affect the severity of COVID-19 disease. It is important that the levels of essential elements and vitamin D are at certain levels for the healthy functioning of the immune system. Therefore, in this study, it was aimed to evaluate immunotoxicity biomarkers (tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10, interferon (IFN)-γ, monocyte chemotactic protein-1 (MCP-1)), vitamin D, and essential element levels in COVID-19 patients in Turkey. According to the results of the study, it was found that the magnesium (Mg), zinc (Zn), and selenium (Se) levels decreased as the severity of the disease worsened, while the iron (Fe), and copper (Cu) levels were similar to the mild group and the control group, and the levels decreased as the disease worsened. It has also been found that vitamin D levels decrease as the severity of the disease worsens. Compared to the control group, TNF-α, MCP-1, and IFN-γ levels were found to decrease as the severity of the disease worsened. Also, it was observed that there was a significant relationship between essential metal levels and disease progression in most of the patient groups.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae177"},"PeriodicalIF":2.2,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11491277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142491347","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 : 2024-10-19eCollection Date: 2024-10-01DOI: 10.1093/toxres/tfae170
Khalida Naseem, Sana Asghar, Kiky Corneliasari Sembiring, Mohammad Ehtisham Khan, Asima Hameed, Shazma Massey, Warda Hassan, Aneela Anwar, Haneef Khan, Faluk Shair
{"title":"Fabrication of bio-inorganic metal nanoparticles by low-cost lychee extract for wastewater remediation: a mini-review.","authors":"Khalida Naseem, Sana Asghar, Kiky Corneliasari Sembiring, Mohammad Ehtisham Khan, Asima Hameed, Shazma Massey, Warda Hassan, Aneela Anwar, Haneef Khan, Faluk Shair","doi":"10.1093/toxres/tfae170","DOIUrl":"10.1093/toxres/tfae170","url":null,"abstract":"<p><strong>Introduction: </strong>This review article gives an overview of the biogenic synthesis of metal nanoparticles (mNPs) while using <i>Litchi chinensis</i> extract as a reducing and stabilizing agent. The subtropical fruit tree i.e lychee contains phytochemicals such as flavonoids, terpenoids, and polyphenolic compounds which act as reducing agents and convert the metal ions into metal atoms that coagulate to form mNPs.</p><p><strong>Methodology: </strong>Different methodologies adopted for the synthesis of lychee extract and its use in the fabrication of mNPs under different reaction conditions such as solvent, extract amount, temperature, and pH of the medium have also been discussed critically in detail.</p><p><strong>Techniques: </strong>Different techniques such as FTIR, UV-visible, XRD, SEM, EDX, and TEM adopted for the analysis of biogenic synthesis of mNPs have also been discussed in detail. Applications of mNPs: Applications of these prepared mNPs in various fields due to their antimicrobial, antiinflammatory, anticancer, and catalytic activities have also been described in detail.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae170"},"PeriodicalIF":2.2,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490315/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453739","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":"Liquid chromatography-high-resolution mass spectrometry-based metabolomics revealing the effects of zearalenone and alpha-zearalenol on human endometrial cancer cells.","authors":"Marhaba Marhaba, Narendra Kumar Nagendla, Saria Anjum, Sireesha Ganneru, Varsha Singh, Saurabh Pal, Mohana Krishna Reddy Mudiam, Kausar Mahmood Ansari","doi":"10.1093/toxres/tfae169","DOIUrl":"https://doi.org/10.1093/toxres/tfae169","url":null,"abstract":"<p><p>Human exposure to mycotoxins through food involve a mixture of compounds, which can be harmful to human health. The Fusarium fungal species are known to produce zearalenone (ZEN), a non-steroidal estrogenic mycotoxin, and its metabolite alpha-zearalenol (α-ZEL), both of which possess endocrine-disruptive properties. Given their potential harm to human health through food exposure, investigating the combined effects of ZEN and α-ZEL becomes crucial. Hence, the combined impact of ZEN and α-ZEL study hold significant importance. This in vitro study delves into the critical area, examining their combined impact on the proliferation and metabolic profile of endometrial cancer Ishikawa cells via sulforhodamine, clonogenic, proliferating cell nuclear antigen (PCNA) and liquid chromatography-high resolution mass spectrometry (LC-HRMS) based untargeted metabolomics. Low concentrations of ZEN (25 nm), α-ZEL (10 nm), or a combination of both were observed to significantly enhance cell proliferation of Ishikawa cells, as evidenced by PCNA immunostaining, immunoblotting as well and clonogenic assays. The metabolomics revealed the perturbations in glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and phenylalanine, tyrosine, tryptophan biosynthesis provides valuable insights into potential mechanism by which these mycotoxins may facilitate cell proliferation. However, further investigations are warranted to comprehensively understand the implications of these findings and their possible implications for human health.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae169"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453741","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 : 2024-10-15eCollection Date: 2024-10-01DOI: 10.1093/toxres/tfae175
Azhar M Elwan, Ibrahim M Farag, Mohamed M M Elnasharty
{"title":"Liver toxicity and repair evaluated by histopathology and electric modulus.","authors":"Azhar M Elwan, Ibrahim M Farag, Mohamed M M Elnasharty","doi":"10.1093/toxres/tfae175","DOIUrl":"https://doi.org/10.1093/toxres/tfae175","url":null,"abstract":"<p><p>Detoxification is one of the most important liver functions. Therefore, liver is the front line of defense when the biosystem faces drug overdose, toxins, and anything that may cause harm. Some famous antibiotics are known for their side effects on liver; one of them is amoxicillin, AM. This work has investigated the toxic effect of amoxicillin on rat's liver with overdose (90 mg/kg) and has studied the ameliorative role of protective and therapeutic Ashwagandha seeds extract (ASE) at doses (100, 200, and 300 mg/kg) against this toxicity. To achieve this work, the authors used two modalities; the first is liver histopathology to figure out the amoxicillin and ASE effects and to detect the sensitivity of another modality; the electric modulus, and its related thermodynamic parameters of liver tissue. Histopathological examination showed that the role of therapeutic ASE in reducing amoxicillin (AM) toxicity was more effective than the protective one. Also, most dielectric and thermodynamic results achieved the same result. Histopathology confirmed the liver injury by amoxicillin and the partial repair by the biosystem using ASE. Moreover, electric modulus, related dielectric parameters, and their thermodynamic state functions showed different changes in their values under the effect of amoxicillin. Using ASE helped the biosystem to restore these changes near their control values.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae175"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474245/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453742","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":"4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) exposure induces hepatotoxicity and nephrotoxicity - role of oxidative stress, mitochondrial dysfunction and pathways of cytotoxicity.","authors":"Gobichettipalayam Balasubramaniam Maadurshni, Manikandan Nagarajan, Balamurali Mahalakshmi, Jeganathan Sivasubramanian, Vedagiri Hemamalini, Jeganathan Manivannan","doi":"10.1093/toxres/tfae173","DOIUrl":"https://doi.org/10.1093/toxres/tfae173","url":null,"abstract":"<p><strong>Objective: </strong>Bisphenol A (BPA) is a ubiquitous pollutant worldwide and 4-Methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP) is considered a major active metabolite of BPA with a wide range of potent toxicological properties. However, its adverse outcome pathway (AOP) on the hepatic and renal system has not yet been explored.</p><p><strong>Methods: </strong>Hence, the current study evaluated its effect on cell survival, oxidative stress, and apoptosis. In addition, the influence of signalling pathways on cytotoxicity and ROS generating enzymes (NOX2 and XO) on oxidative stress was explored by siRNA knockdown experiments. Further, its molecular interaction with SOD, CAT, and HSA (molecular docking and dynamics) was evaluated and validated with spectroscopy (fluorescence and FTIR) based methods.</p><p><strong>Results: </strong>The outcome indicates that MBP exposure dose dependently increased the cytotoxic response, oxidative stress, and apoptosis in both hepatocytes and kidney cells. Further, MAPK signalling pathways and oxidative stress influenced the overall cytotoxic response in both cells. In addition, the stimulatory (NOX2 and XO) and inhibitory (SOD and CAT) effects of MBP were observed, along with a robust interaction with HSA.</p><p><strong>Conclusions: </strong>The overall observation illustrates that MBP exposure adversely impacts hepatic and renal cells through oxidative stress and relevant molecular pathways which may connect the missing links during risk assessment of BPA.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"13 5","pages":"tfae173"},"PeriodicalIF":2.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11474237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453735","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}