Toxicology ResearchPub Date : 2023-07-03eCollection Date: 2023-08-01DOI: 10.1093/toxres/tfad053
Zahraa K Sobh, Maha Ghanem, Marwa Kholief
{"title":"Physicians' perspectives on different therapeutic approaches for aluminum phosphide poisoning and their relevant outcomes.","authors":"Zahraa K Sobh, Maha Ghanem, Marwa Kholief","doi":"10.1093/toxres/tfad053","DOIUrl":"10.1093/toxres/tfad053","url":null,"abstract":"<p><strong>Background: </strong>Aluminum phosphide is a highly toxic pesticide that results in high mortality. To date, there is neither a definitive antidote nor a unified protocol for managing acute aluminum phosphide poisoning.</p><p><strong>Objectives: </strong>This cross-sectional questionnaire-based study aims to explore different management approaches and rely on the expertise of Egyptian medical professionals to enhance the prognosis for acute aluminum phosphide poisoning.</p><p><strong>Subjects and methods: </strong>A self-administered questionnaire was formulated and electronically distributed according to published literature and experience of senior physicians.</p><p><strong>Results and conclusions: </strong>Responses were received from 151 physicians from 10 governorates. Management modalities were variable among respondents. Noradrenaline was used by 90.7% of respondents with no fixed-dose regimen. In all, 84.1% of participants utilized oil in gastrointestinal decontamination; paraffin oil was the most used solution. Overall, 92.1, 61.6, 46.4, and 34.4% of participants used sodium bicarbonate, proton pump inhibitors, IV magnesium sulfate, and antioxidants, respectively. Regarding the frequency of acute aluminum phosphide poisoning, 47% of participants managed these cases daily or a few times a week. Participants' responses denoted a poor prognosis of acute aluminum phosphide poisoning, and high percentages attributed the prognosis to exposure factors rather than treatment modalities. Statistical analysis revealed that using oil in gastrointestinal decontamination improved the outcome by 4.62-fold. Clinical toxicologists were more likely to rescue ≥ 30% of the cases about 3-fold (2.97) than other specialties. Clinical toxicologists used oil in gastrointestinal decontamination, magnesium sulfate, and antioxidant therapy and calculated base deficit before administration of sodium bicarbonate by 7.70-, 5.30-, 3.26-, and 2.08-fold than other specialties.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"615-625"},"PeriodicalIF":2.2,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10151909","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 : 2023-07-03eCollection Date: 2023-08-01DOI: 10.1093/toxres/tfad049
Hasan Saç, Aslı Ç Yeltekin
{"title":"Investigation of oxidative stress status and apoptotic markers of juvenile trout exposed to arsenic toxicity.","authors":"Hasan Saç, Aslı Ç Yeltekin","doi":"10.1093/toxres/tfad049","DOIUrl":"10.1093/toxres/tfad049","url":null,"abstract":"<p><p>Arsenic is one of the most abundant elements on earth. Arsenic, also called metalloid, is used as a raw material in many industries. Arsenic causes the acceleration of free radical production in the body and the resulting oxidative stress. In juvenile trout, the interactions of arsenic with metacomposition, biochemical analysis, and apoptosis stimuli were investigated. Results were demonstrated by several marker applications, including oxidative stress parameters, proinflammatory cytokine expressions, DNA damage, and apoptosis markers. In our study, arsenic was applied to juvenile trout (<i>Oncorhynchus mykiss</i>) at concentrations of 25, 50, and 75 mg/L for 96 h. After exposure, the brain tissues of the fish were collected and homogenized. SOD the GSH-Px, CAT, and MDA levels were determined by spectrophotometric methods in the supernatants from the brain tissues of the juvenile trout. Levels of NF-kB, TNF-α, IL-6, Nrf-2, GSH, caspase-3, AChE, and 8-OHdG were determined with an ELISA kit. When the brain tissues of the fish were examined after the study, it was found that the levels of NF-kB, TNF-α, IL-6, Nrf-2, Caspza-3, MDA, and 8-OHdG increased, and the levels of GSH, CAT, SOD, AChE, and GSH-Px decreased. It was found that oxidative stress occurred as a result of the effect of the heavy metal arsenic in the brain tissues of the fish after application.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"608-614"},"PeriodicalIF":2.2,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10150395","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 : 2023-06-30eCollection Date: 2023-08-01DOI: 10.1093/toxres/tfad051
Ghada A Sagah, Manar M Fayed
{"title":"Body mass index as a predictor of the outcomes of acute clozapine toxicity: a cross-sectional study.","authors":"Ghada A Sagah, Manar M Fayed","doi":"10.1093/toxres/tfad051","DOIUrl":"10.1093/toxres/tfad051","url":null,"abstract":"<p><p>Acute antipsychotic overdose is frequently reported nowadays. Clozapine is one of the atypical agents that are highly lipophilic, highly protein-bound, has a large volume of distribution, and accumulates in the brain and other tissues. Obesity is an essential factor controlling patients' treatment and clinical course. The current study aimed to study the prognostic value of body mass index (BMI) in patients with acute clozapine poisoning. All patients were evaluated on admission using the Poison Severity Score (PSS) and Glasgow Coma Score (GCS). The BMI was calculated. Mortality and the need for ICU admission were defined as primary outcomes, whereas secondary outcomes included cardiovascular complications and the need for mechanical ventilation. Thirty-eight patients presented with acute clozapine poisoning. The mean age of included patients was 25.2 ± 6. Patients were categorized regarding BMI into average weight (26.3%), overweight (31.6%), and obese (42.1%). Pearson's correlation indicated a significant positive correlation between BMI and respiratory rate (<i>r</i> = .364, <i>p</i> = .025). A significant negative correlation existed between BMI and GCS (<i>r</i> = .674, <i>p</i> ≤ .001). ROC curve reveals that BMI is an excellent predictor for the requirement of mechanical ventilation area under the curve (AUC > .9), a fair predictor of ICU admission AUC (.747). BMI had a sensitivity of 100% and specificity of 51.7 for the prediction of ICU admission. In conclusion, obesity increased the severity of toxicity and the incidence of poor clinical outcomes in patients with acute clozapine poisoning.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"599-607"},"PeriodicalIF":2.2,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10525132","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":"Phage display technology for fabricating a recombinant monoclonal ScFv antibody against tetanus toxin.","authors":"Hamideh Rouhani Nejad, Jalil Fallah Mehrabadi, Pardis Saeedi, Saeed Zanganeh","doi":"10.1093/toxres/tfad050","DOIUrl":"10.1093/toxres/tfad050","url":null,"abstract":"<p><p>Tetanus is a specific infectious disease, often associated with lower immunization in developing countries and catastrophic events (such as earthquakes). Millions of people, especially children, die every year from tetanus disease. Therefore, it is necessary to devise a rapid and sensitive detection method for tetanus toxin to ensure an early diagnosis and clinical treatment of tetanus. The current study looks at developing a novel, high specific, low-cost, and sensitive ScFv antibody. It is capable of tetanus detection immunoassays in clinical diagnosis, suspicious foods, and water monitoring. For this regard, a high-quality phage display antibody library (8.7 × 10<sup>7</sup> PFU/ml) was constructed. Tetanus-specific antibodies with high affinity retrieved from libraries. After phage rescue and four rounds of biopanning, clone screening was performed by phage ELISA. Recombinant antibodies expressed from the AC8 clone showed the highest affinity for tetanus. SDS-PAGE and western blotting confirmed the presence of a high-quality, pure ScFv band at 32 kDa. ELISA was used to determine the affinity value, estimated to be around 10<sup>-8</sup> M. The results suggest that the proposed detection method by ScFv antibodies is an alternative diagnostic tool enabling rapid and specific detection of the tetanus toxin.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"591-598"},"PeriodicalIF":2.2,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10151908","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 : 2023-06-26eCollection Date: 2023-08-01DOI: 10.1093/toxres/tfad052
Nazmiye Bıtgen, Gozde Ozge Onder, Munevver Baran, Arzu Yay
{"title":"Cytotoxicity screening of <i>Thymus vulgaris</i> L. in breast cancer: in vitro study.","authors":"Nazmiye Bıtgen, Gozde Ozge Onder, Munevver Baran, Arzu Yay","doi":"10.1093/toxres/tfad052","DOIUrl":"10.1093/toxres/tfad052","url":null,"abstract":"<p><p>Breast cancer is one of the leading causes of cancer-related deaths due to its aggressive course. There is an increasing need for alternative therapy strategies, including herbal medications, to treat the disease because of its high incidence. Medicinal plants, such as <i>Thymus vulgaris</i> L. (<i>T. vulgaris</i>), have recently attracted great interest due to the antitumor properties of their extracts. The purpose of this investigation was to ascertain whether <i>T. vulgaris</i> had any cytotoxic effects on two different breast cancer cell lines. MTT test was applied to evaluate the effect of <i>T. vulgaris</i> on cell viability. TUNEL method was used to determine its apoptotic effect. LC3 and Beclin-1 expression levels were determined by immunofluorescence staining method and its autophagic effect was evaluated. Our findings demonstrate that <i>T. vulgaris</i> greately lowers proliferation, both in terms of concentration and duration. Consistent with decreased proliferation, an increase in apoptotic and autophagic cell death were also observed. The migration capacity of MCF-7 and MDA-MB-231 breast cancer cells was greatly suppressed by <i>T. vulgaris</i>, while significantly reducing colony formation. This study is the first to look into how <i>T. vulgaris</i> methanol extract affects breast cancer cells. All of these findings demonstrate that <i>T. vulgaris</i> prevents breast cancer cells from developing a malignant phenotype. It is possible to say that the methanol extract of <i>T. vulgaris</i> is suitable for the treatment of breast cancer, including aggressive types. However, in vivo research should support these results.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"584-590"},"PeriodicalIF":2.2,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10143891","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 : 2023-06-24eCollection Date: 2023-08-01DOI: 10.1093/toxres/tfad047
Hasan Huseyin Demirel, Fahriye Zemheri-Navruz, İsmail Kucukkurt, Damla Arslan-Acaroz, Ali Tureyen, Sinan Ince
{"title":"Synergistic toxicity of 2,4-dichlorophenoxyacetic acid and arsenic alters biomarkers in rats.","authors":"Hasan Huseyin Demirel, Fahriye Zemheri-Navruz, İsmail Kucukkurt, Damla Arslan-Acaroz, Ali Tureyen, Sinan Ince","doi":"10.1093/toxres/tfad047","DOIUrl":"10.1093/toxres/tfad047","url":null,"abstract":"<p><p>2,4-dichlorophenoxyacetic acid (2,4-D) and arsenic cause severe and extensive biological toxicity in organisms. However, their interactions and toxic mechanisms in co-exposure remain to be fully elucidated. In this study, 28 four-week-old female rats were divided into four groups and exposed to 100 mg/L arsenic or/and 600 mg/L 2,4-D through drinking water for a period of 28 days. As a result, it was revealed that biochemical indicators (ALT, AST, ALP, blood urea nitrogen, and creatinine) were increased and decreased hormonal parameters (FSH, LH, PG, and E2) in arsenic and 2,4-D and arsenic combination-treated groups. Moreover, increased lipid peroxidation (malondialdehyde level) and decreased antioxidant status (superoxide dismutase and catalase activities) were found in the co-exposure groups compared with the individual-exposure groups. Meanwhile, severe DNA damage was observed in co-exposure groups. Additionally, the levels of apoptotic <i>(Bax, Caspase-3, Caspase-8, Caspase-9, p53,</i> and <i>PARP</i>) and inflammation (<i>NFκB, Cox-2, TNF-</i>α<i>,</i> and <i>TGFβI</i>) indexes in the co-exposure groups were markedly increased, whereas the levels of anti-apoptosis index (<i>Bcl-2</i>) were decreased. It was also observed that co-exposure with 2,4-D and arsenic caused more histopathological changes in tissues. Generally, these results show that co-exposure to 2,4-D and arsenic can seriously cause oxidative stress, DNA damage, apoptosis and inflammation while having toxicological risk for organisms.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"574-583"},"PeriodicalIF":2.2,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470338/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10151907","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 : 2023-06-21eCollection Date: 2023-08-01DOI: 10.1093/toxres/tfad046
Lingmei Ma, Chunyan Ling, Shuning Hu, Sudan Ye, Chun Chen
{"title":"High-throughput transcriptome sequencing reveals the protective role of adenosine receptor-related genes in paraquat-exposed <i>Caenorhabditis elegans</i>.","authors":"Lingmei Ma, Chunyan Ling, Shuning Hu, Sudan Ye, Chun Chen","doi":"10.1093/toxres/tfad046","DOIUrl":"10.1093/toxres/tfad046","url":null,"abstract":"<p><p>This study sought to identify the genes associated with adenosine's protective action against paraquat (PQ)-induced oxidative stress via the adenosine receptor (ADOR-1) in <i>Caenorhabditis elegans</i> (<i>C. elegans</i>). The <i>C. elegans</i> was divided into 3 groups-2 groups exposed to PQ, one in presence, and one in absence of adenosine-and a control group that was not treated. Each group's total RNA was extracted and sequenced. When the transcriptomes of these groups were analyzed, several genes were found to be differently expressed. These differentially expressed genes were significantly enriched in adenosine-response biological processes and pathways, including gene ontology terms related to neuropeptide and kyoto encyclopedia of genes and genomes pathways associated to cAMP pathway regulator activity. Quantitative reverse-transcription PCR confirmed that G-protein-coupled receptors signaling pathway involving <i>dop-1</i>, <i>egl-30</i>, <i>unc-13</i>, <i>kin-1</i>, and <i>goa-1</i> genes may play crucial roles in modulating adenosine's protective action. Interestingly, there are no significant variations in the expression of the <i>ador-1</i> gene across the 3 treatments, thereby indicating that adenosine receptor exerts a consistent and stable influence on its related pathways irrespective of the presence or absence of PQ. Furthermore, the wild-type group with <i>ador-1</i> gene has higher survival rate than that of the <i>ador-1</i><sup>-</sup>/RNA interference group while treated with PQ in the presence of adenosine. Conclusively, our study uncovered a number of novel PQ-response genes and adenosine receptor-related genes in <i>C. elegans</i>, which may function as major regulators of PQ-induced oxidative stress and indicate the possible protective effects of adenosine.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"564-573"},"PeriodicalIF":2.2,"publicationDate":"2023-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10525137","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 : 2023-06-14eCollection Date: 2023-08-01DOI: 10.1093/toxres/tfad042
Graham J Urquhart, Matthew Symington, Kerry Foxall, Henrietta Harrison, Ovnair Sepai
{"title":"Using science to respond to public exposures from chemical hazards during emergencies in England.","authors":"Graham J Urquhart, Matthew Symington, Kerry Foxall, Henrietta Harrison, Ovnair Sepai","doi":"10.1093/toxres/tfad042","DOIUrl":"10.1093/toxres/tfad042","url":null,"abstract":"<p><p>This paper describes how toxicological considerations are an essential component of acute chemical incident response, and how the UK Health Security Agency (UKHSA), as Category 1 responders under the Civil Contingencies Act (2004), provide that expert, authoritative, and timely advice to protect people from exposure to harmful substances. Background information about the general response to emergencies is provided, which gives context to how scientific advice has a positive impact. The importance of chemical identification and speciation, local, and systemic effects, and exposure characteristics are described. The public health risk assessment is considered in conjunction with mixtures, mass casualties, recovery, and psychological impacts. A brief summary of the type of incidents that the UKHSA are notified about is also provided.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"539-543"},"PeriodicalIF":2.1,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10143888","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":"Casein and pea enriched high-protein diet attenuates arsenic provoked apoptosis in testicles of adult rats.","authors":"Sagnik Biswas, Priyankar Pal, Rubia Mondal, Prabir Kumar Mukhopadhyay","doi":"10.1093/toxres/tfad043","DOIUrl":"10.1093/toxres/tfad043","url":null,"abstract":"<p><p>Arsenic toxicity is a major health issue that also threats male reproductive system leading to impairment of fertility. The antioxidant capacity of casein and pea enriched formulated high-protein diet (FHPD) is found to be effective in different toxicity management. The present study was endeavored to investigate the mitigatory aspect of FHPD on arsenic stimulated testicular apoptosis. Adult male rats were maintained on either normal diet as control (Gr I, <i>n</i> = 8) and arsenic (As<sub>2</sub>O<sub>3</sub>) treated at a dose of 3 mg/kg/rat/day (Gr II, <i>n</i> = 8) or on isocaloric FHPD as supplemented (Gr III, <i>n</i> = 8) with same dose of arsenic for 30 consecutive days. Testicular histomorphometry, spermatokinetics, testicular functional marker enzymes, serum gonadotrophins, oxidative stress markers, testicular deoxyribonucleic acid (DNA) damage, and apoptosis markers were evaluated to assess the reprotoxicity of arsenic and subsequent protection by FHPD. FHPD protected the histopathological alterations and also restored normal spermatogenesis. Altered enzymatic activities of testicular functional markers like lactate dehydrogenase, γ-glutamyl transferase, acid phosphatase, and alkaline phosphatase were also regularized. FHPD also reinstated the normal level of follicle stimulating hormone (FSH), luteinising hormone (LH), and also normalized the enzymatic activities of testicular glutathione peroxidase and glutathione reductase. Testicular DNA damage was also prevented by FHPD supplementation. Testicular apoptosis marked by the altered messenger ribonucleic acid and protein expression of apoptotic markers like Bax, Bcl-2, caspase 9, and caspase 3 were also attenuated upon FHPD supplementation along with diminution of arsenic accumulation in testicular tissues. FHPD not only mitigated the adverse effects of arsenic induced gonadotoxicity but also helped in sustaining the normal reproductive functions.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"551-563"},"PeriodicalIF":2.1,"publicationDate":"2023-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10143886","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 : 2023-06-06eCollection Date: 2023-08-01DOI: 10.1093/toxres/tfad041
S Shruthi, Kamalesh D Mumbrekar, B S Satish Rao, Bhasker K Shenoy
{"title":"Gallic acid: a polyphenolic compound potentiates the therapeutic efficacy of cisplatin in human breast cancer cells.","authors":"S Shruthi, Kamalesh D Mumbrekar, B S Satish Rao, Bhasker K Shenoy","doi":"10.1093/toxres/tfad041","DOIUrl":"10.1093/toxres/tfad041","url":null,"abstract":"<p><p>Gallic acid (GA) is a natural polyhydroxyphenolic compound with antioxidant, antimutagenic, anti-inflammatory, and antineoplastic activities. Cisplatin (CPT) is a platinum-based chemotherapeutic drug, and it is the treatment of choice for breast, ovarian, testicular, head, and neck cancers. However, the use of anticancer drugs has undesirable effects on patients due to associated toxicities. Thus, it is necessary to search for alternatives that reduce unintended side effects and enhance anticancer potential. The use of natural compounds with the conventional chemotherapeutic drug is a new aspect of cancer therapy. In the present study, we evaluated the ability of GA in the modulation of anticancer effects of CPT in human breast adenocarcinoma cells (MCF-7) by performing MTT, apoptosis, clonogenic cell survival, and micronucleus assays. GA and CPT showed significant cytotoxic activities in MCF-7 cells in a dose-dependent manner. In combination therapy (GA 2.5, 5.0, and 10 μg/mL + CPT10 μg/mL), GA synergistically reduced the MCF-7 cell viability in contrast to the individual therapies. Cancer cells death by GA is through the induction of apoptosis as observed in the acridine orange and ethidium bromide dual staining method. The frequency of micronuclei (MN) was decreased significantly (<i>P</i> < 0.001) in combinational therapy, possibly reducing the risk of chemotherapy-induced MN. Moreover, GA in mono or combinational therapy did not induce any cytotoxic effects in normal breast epithelial cells (MCF-10A). GA did not show any significant difference in colony inhibition compared to CPT. This outcome shows its differential effects in normal and cancerous cells. Hence, the combination GA with chemotherapeutic drugs could represent a promising alternative therapy in cancer treatment with minimal side effects.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"12 4","pages":"544-550"},"PeriodicalIF":2.1,"publicationDate":"2023-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10470337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10143890","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}