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In silico, in vitro and in vivo toxicity assessment of the antitumoral peptide GK-1
Q1 Environmental Science Pub Date : 2025-02-12 DOI: 10.1016/j.toxrep.2025.101962
Sergio Sifontes-Rodríguez , Juan Alberto Hernández-Aceves , Carlos Gerardo Salas- Garrido , Diego Moctezuma Rocha , Iván Nicolás Pérez-Osorio , Nelly Villalobos , Edda Sciutto , Gladis Fragoso
Peptide drugs have emerged as an attractive alternative for cancer treatment due to their potency, high specificity, general safety and low cost. GK-1 is a linear 18 amino acid peptide with proven immunomodulator, antitumor and antimetastatic capacity in animal models. Preclinical toxicity studies for its use as a vaccine adjuvant demonstrated its safety in various assay systems, but a comprehensive exploration of its toxicity profile is required to be used in cancer immunotherapy. Therefore, in the present work, the potential toxicity of GK-1 was predicted with ToxinPred 3.0 software, and its in vitro cytotoxicity, and single-dose and repeated-dose toxicity by subcutaneous route in mice were experimentally assessed. GK-1 peptide was predicted as a non-toxic and did not exhibit in vitro cytotoxicity for several non-tumor and tumor cell lines and primary cell cultures at concentrations up to 500 µM, reinforcing previous studies pointing that the antitumoral effect of GK-1 was not mediated by tumor cell cytotoxicity. The single-dose toxicity study did not evidence local or systemic toxicity up to the maximum tested dose of 1000 mg/kg. Moreover, no toxic effects were observed in the repeated-dose toxicity study based on four doses administered weekly at up to 300 mg/kg. Considering that GK-1 is effective in triple-negative breast cancer and melanoma models in mice at doses as low as 5 mg/kg, the present results support the safety of GK-1 as an antitumoral peptide candidate.
{"title":"In silico, in vitro and in vivo toxicity assessment of the antitumoral peptide GK-1","authors":"Sergio Sifontes-Rodríguez ,&nbsp;Juan Alberto Hernández-Aceves ,&nbsp;Carlos Gerardo Salas- Garrido ,&nbsp;Diego Moctezuma Rocha ,&nbsp;Iván Nicolás Pérez-Osorio ,&nbsp;Nelly Villalobos ,&nbsp;Edda Sciutto ,&nbsp;Gladis Fragoso","doi":"10.1016/j.toxrep.2025.101962","DOIUrl":"10.1016/j.toxrep.2025.101962","url":null,"abstract":"<div><div>Peptide drugs have emerged as an attractive alternative for cancer treatment due to their potency, high specificity, general safety and low cost. GK-1 is a linear 18 amino acid peptide with proven immunomodulator, antitumor and antimetastatic capacity in animal models. Preclinical toxicity studies for its use as a vaccine adjuvant demonstrated its safety in various assay systems, but a comprehensive exploration of its toxicity profile is required to be used in cancer immunotherapy. Therefore, in the present work, the potential toxicity of GK-1 was predicted with ToxinPred 3.0 software, and its <em>in vitro</em> cytotoxicity, and single-dose and repeated-dose toxicity by subcutaneous route in mice were experimentally assessed. GK-1 peptide was predicted as a non-toxic and did not exhibit <em>in vitro</em> cytotoxicity for several non-tumor and tumor cell lines and primary cell cultures at concentrations up to 500 µM, reinforcing previous studies pointing that the antitumoral effect of GK-1 was not mediated by tumor cell cytotoxicity. The single-dose toxicity study did not evidence local or systemic toxicity up to the maximum tested dose of 1000 mg/kg. Moreover, no toxic effects were observed in the repeated-dose toxicity study based on four doses administered weekly at up to 300 mg/kg. Considering that GK-1 is effective in triple-negative breast cancer and melanoma models in mice at doses as low as 5 mg/kg, the present results support the safety of GK-1 as an antitumoral peptide candidate.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101962"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to: “Co-delivery of methotrexate and berberine based on PAMAM dendrimers for targeting HeLa cancer cells” [Toxicol. Rep. Volume 13, December 2024, 101765]
Q1 Environmental Science Pub Date : 2025-02-12 DOI: 10.1016/j.toxrep.2025.101957
Hossein Majidzadeh , Mostafa Araj-Khodaei , Ayuob Aghanejad , Maryam Ghaffari , Amir Jafari , Forough Jenanifard , Jafar Ezzati Nazhad Dolatabadi , Hashem Andishmand , Michael R. Hamblin
{"title":"Corrigendum to: “Co-delivery of methotrexate and berberine based on PAMAM dendrimers for targeting HeLa cancer cells” [Toxicol. Rep. Volume 13, December 2024, 101765]","authors":"Hossein Majidzadeh ,&nbsp;Mostafa Araj-Khodaei ,&nbsp;Ayuob Aghanejad ,&nbsp;Maryam Ghaffari ,&nbsp;Amir Jafari ,&nbsp;Forough Jenanifard ,&nbsp;Jafar Ezzati Nazhad Dolatabadi ,&nbsp;Hashem Andishmand ,&nbsp;Michael R. Hamblin","doi":"10.1016/j.toxrep.2025.101957","DOIUrl":"10.1016/j.toxrep.2025.101957","url":null,"abstract":"","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101957"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus
Q1 Environmental Science Pub Date : 2025-02-10 DOI: 10.1016/j.toxrep.2025.101958
Fouad Kasim Mohammad , Rawnaq Faris Al-Shalchi
Dyslipidemic statins reduce blood and brain cholinesterase (ChE) activities in mice, with scarce information on other protein/enzyme targets. The study aims at conducting a mini meta-analysis on in vivo and in vitro adverse anti-ChE effects of atorvastatin, simvastatin and rosuvastatin in mice, and using the SwissPrediction to identify in silico body target proteins. The data comprised 72 records of plasma, erythrocytes and brain ChE activities, expressed as percent mean ± SD of respective controls. We conducted a randomized effects size single-arm meta-analysis. The risk of bias scoring was according to those of animal experiments. The effect size (% ChE activity) of statin treatments was significantly decreased by 25.85 % (combined effect size=74.15, p = 0.0001), with significant heterogeneity (Q=1133.19, p < 0.0001, I2=93.73 %). Subgroup analysis was significantly dose and concentration-dependent. The funnel plot showed non-symmetrical data distribution, with no imputed points. The risk of bias was moderate. In silico mouse body protein targets for the statins were mainly classes of Family AG protein- coupled receptor (20.0 %-33.3 %), Oxidoreductase (6.7–13.3 %) and Eraser (13.3 % each), with others at 0–26.7 %. The findings highlight statin effects in mice by reducing blood and brain ChE activities, in a dose/concentration-dependent manner, that would potentially modulate the cholinergic system. This anti-ChE effect together with in silico protein targets recognized could be the basis of further experimental explorations of adverse effects of statins.
{"title":"Mini meta-analysis of anticholinesterase actions of atorvastatin, simvastatin and rosuvastatin, and in silico identification of their protein targets in Mus musculus","authors":"Fouad Kasim Mohammad ,&nbsp;Rawnaq Faris Al-Shalchi","doi":"10.1016/j.toxrep.2025.101958","DOIUrl":"10.1016/j.toxrep.2025.101958","url":null,"abstract":"<div><div>Dyslipidemic statins reduce blood and brain cholinesterase (ChE) activities in mice, with scarce information on other protein/enzyme targets. The study aims at conducting a mini meta-analysis on <em>in vivo</em> and <em>in vitro</em> adverse anti-ChE effects of atorvastatin, simvastatin and rosuvastatin in mice, and using the SwissPrediction to identify <em>in silico</em> body target proteins. The data comprised 72 records of plasma, erythrocytes and brain ChE activities, expressed as percent mean ± SD of respective controls. We conducted a randomized effects size single-arm meta-analysis. The risk of bias scoring was according to those of animal experiments. The effect size (% ChE activity) of statin treatments was significantly decreased by 25.85 % (combined effect size=74.15, p = 0.0001), with significant heterogeneity (<em>Q</em>=1133.19, p &lt; 0.0001, I<sup>2</sup>=93.73 %). Subgroup analysis was significantly dose and concentration-dependent. The funnel plot showed non-symmetrical data distribution, with no imputed points. The risk of bias was moderate. <em>In silico</em> mouse body protein targets for the statins were mainly classes of Family AG protein- coupled receptor (20.0 %-33.3 %), Oxidoreductase (6.7–13.3 %) and Eraser (13.3 % each), with others at 0–26.7 %. The findings highlight statin effects in mice by reducing blood and brain ChE activities, in a dose/concentration-dependent manner, that would potentially modulate the cholinergic system. This anti-ChE effect together with <em>in silico</em> protein targets recognized could be the basis of further experimental explorations of adverse effects of statins.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101958"},"PeriodicalIF":0.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Protective effects of Allium sativum essential oil against lead nitrate-induced cardiotoxicity: Modulation of lipid metabolism, nitric oxide dynamics, inflammatory mediators, and histological profiles in Swiss albino mice
Q1 Environmental Science Pub Date : 2025-02-09 DOI: 10.1016/j.toxrep.2025.101950
Anjali Rajpoot , Veena Sharma

Background

Lead (Pb²⁺) is a toxic metal known to induce oxidative stress and inflammation, contributing to cardiovascular diseases such as hypertension and atherosclerosis. Natural compounds like Allium sativum essential oil (ASEO) offer potential therapeutic benefits against lead-induced damage, but their cardioprotective effects remain underexplored. This study investigates the efficacy of ASEO in mitigating cardiovascular toxicity induced by lead nitrate in male Swiss albino mice.

Methods

Thirty-six male mice were divided into six groups: Control, Lead Nitrate (50 mg/kg), Lead Nitrate + Low-dose ASEO (50 mg/kg), Lead Nitrate + High-dose ASEO (80 mg/kg), Lead Nitrate + Silymarin (25 mg/kg), and Lead Nitrate + Olive Oil. After 12 days of lead exposure, treatments were administered for 30 days. Key cardiovascular parameters such as lipid profiles (total cholesterol, LDL, HDL), nitric oxide (NO), and inflammatory markers (TNF-α, IL-6, IFN-γ, IL-10, NF-κB) were evaluated alongside histological analysis of cardiac tissue.

Results

Lead nitrate exposure significantly increased total cholesterol (88.27 µg/mL) and LDL (93.78 µg/mL) while reducing HDL (17.51 µg/mL) compared to controls (P < 0.001). High-dose ASEO lowered total cholesterol (66.07 µg/mL) and LDL (49.62 µg/mL) while increased HDL (27.2 µg/mL) (P < 0.001). NO levels, reduced by lead exposure, were significantly restored by high-dose ASEO (P < 0.001). Inflammatory markers, including TNF-α, NF-kB, and IL-6, were elevated in the lead group but decreased significantly following ASEO treatment (P < 0.001). Histological analysis showed that ASEO markedly preserved myocardial architecture, reducing degeneration and inflammation.

Conclusion

High-dose ASEO demonstrated significant cardioprotective effects against lead-induced toxicity by improving lipid profiles, enhancing NO levels, and modulating inflammatory markers. Further studies are warranted to validate these results.
{"title":"Protective effects of Allium sativum essential oil against lead nitrate-induced cardiotoxicity: Modulation of lipid metabolism, nitric oxide dynamics, inflammatory mediators, and histological profiles in Swiss albino mice","authors":"Anjali Rajpoot ,&nbsp;Veena Sharma","doi":"10.1016/j.toxrep.2025.101950","DOIUrl":"10.1016/j.toxrep.2025.101950","url":null,"abstract":"<div><h3>Background</h3><div>Lead (Pb²⁺) is a toxic metal known to induce oxidative stress and inflammation, contributing to cardiovascular diseases such as hypertension and atherosclerosis. Natural compounds like Allium sativum essential oil (ASEO) offer potential therapeutic benefits against lead-induced damage, but their cardioprotective effects remain underexplored. This study investigates the efficacy of ASEO in mitigating cardiovascular toxicity induced by lead nitrate in male Swiss albino mice.</div></div><div><h3>Methods</h3><div>Thirty-six male mice were divided into six groups: Control, Lead Nitrate (50 mg/kg), Lead Nitrate + Low-dose ASEO (50 mg/kg), Lead Nitrate + High-dose ASEO (80 mg/kg), Lead Nitrate + Silymarin (25 mg/kg), and Lead Nitrate + Olive Oil. After 12 days of lead exposure, treatments were administered for 30 days. Key cardiovascular parameters such as lipid profiles (total cholesterol, LDL, HDL), nitric oxide (NO), and inflammatory markers (TNF-α, IL-6, IFN-γ, IL-10, NF-κB) were evaluated alongside histological analysis of cardiac tissue.</div></div><div><h3>Results</h3><div>Lead nitrate exposure significantly increased total cholesterol (88.27 µg/mL) and LDL (93.78 µg/mL) while reducing HDL (17.51 µg/mL) compared to controls (<em>P</em> &lt; 0.001). High-dose ASEO lowered total cholesterol (66.07 µg/mL) and LDL (49.62 µg/mL) while increased HDL (27.2 µg/mL) (<em>P</em> &lt; 0.001). NO levels, reduced by lead exposure, were significantly restored by high-dose ASEO (<em>P</em> &lt; 0.001). Inflammatory markers, including TNF-α, NF-kB, and IL-6, were elevated in the lead group but decreased significantly following ASEO treatment (<em>P</em> &lt; 0.001). Histological analysis showed that ASEO markedly preserved myocardial architecture, reducing degeneration and inflammation.</div></div><div><h3>Conclusion</h3><div>High-dose ASEO demonstrated significant cardioprotective effects against lead-induced toxicity by improving lipid profiles, enhancing NO levels, and modulating inflammatory markers. Further studies are warranted to validate these results.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101950"},"PeriodicalIF":0.0,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Environmental health risks and impacts of PM2.5 exposure on human health in residential areas, Bantul, Yogyakarta, Indonesia
Q1 Environmental Science Pub Date : 2025-02-05 DOI: 10.1016/j.toxrep.2025.101949
Azham Umar Abidin , Anisful Lailil Munawaroh , Aulia Rosinta , Arvi Tri Sulistiyani , Iwan Ardianta , Fajri Mulya Iresha
Air pollution, particularly PM2.5, significantly impacts public health in developing areas. This study evaluates PM2.5 exposure among residents and conducts a health risk assessment within the human community in Bantul Regency, Indonesia, utilizing a high-volume air sampler (HVAS) over 24 h in a residential area and interviewing 36 respondents. The findings of this study show that PM2.5 concentrations varied from 50.7 to 61.9 μg/m³, exceeding the national ambient air quality standards (NAAQS) of 35 μg/m³. The risk hazard quotient (RQ) values of PM2.5 were greater than 1, signifying considerable health risk. Epidemiological statistical analysis indicates a significant correlation (p-value < 0.05) between PM2.5 exposure, health complaints, and respondent characteristics. Residents report health issues including cough, headache, eye irritation, breathlessness, and wheezing. The findings emphasize the imperative for more rigorous air quality standards and regulations, enhanced public awareness and education regarding preventive practices, and urban planning development strategies incorporating green infrastructure. These measures are crucial for alleviating health hazards and enhancing air quality in impacted areas.
{"title":"Environmental health risks and impacts of PM2.5 exposure on human health in residential areas, Bantul, Yogyakarta, Indonesia","authors":"Azham Umar Abidin ,&nbsp;Anisful Lailil Munawaroh ,&nbsp;Aulia Rosinta ,&nbsp;Arvi Tri Sulistiyani ,&nbsp;Iwan Ardianta ,&nbsp;Fajri Mulya Iresha","doi":"10.1016/j.toxrep.2025.101949","DOIUrl":"10.1016/j.toxrep.2025.101949","url":null,"abstract":"<div><div>Air pollution, particularly PM<sub>2.5</sub>, significantly impacts public health in developing areas. This study evaluates PM<sub>2.5</sub> exposure among residents and conducts a health risk assessment within the human community in Bantul Regency, Indonesia, utilizing a high-volume air sampler (HVAS) over 24 h in a residential area and interviewing 36 respondents. The findings of this study show that PM<sub>2.5</sub> concentrations varied from 50.7 to 61.9 μg/m³, exceeding the national ambient air quality standards (NAAQS) of 35 μg/m³. The risk hazard quotient (RQ) values of PM<sub>2.5</sub> were greater than 1, signifying considerable health risk. Epidemiological statistical analysis indicates a significant correlation (p-value &lt; 0.05) between PM<sub>2.5</sub> exposure, health complaints, and respondent characteristics. Residents report health issues including cough, headache, eye irritation, breathlessness, and wheezing. The findings emphasize the imperative for more rigorous air quality standards and regulations, enhanced public awareness and education regarding preventive practices, and urban planning development strategies incorporating green infrastructure. These measures are crucial for alleviating health hazards and enhancing air quality in impacted areas.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101949"},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143379150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fish consumption patterns and health risk assessment of polycyclic aromatic hydrocarbons and polychlorinated biphenyls in fried and grilled fish products and mitigation strategies
Q1 Environmental Science Pub Date : 2025-02-05 DOI: 10.1016/j.toxrep.2025.101953
Abhishek , S. Chakkaravarthi , Tripti Agarwal
In the present study, the concentration of 13PAHs and the six indicator PCBs was determined through GC-MS/MS in 36 grilled and fried fish products. The study is unique in terms of the simultaneous determination of two types of persistent organic pollutants in grilled and fried fish products. The concentration of ∑13PAHs and ∑6PCBs in these samples varied from 20.80 ± 2.06–947.65 ± 40.85 µg kg−1 and 2.86 ± 0.16–46.52 ± 0.46 µg kg−1, respectively. Dietary exposure and human health risks due to the consumption of fried and grilled fish products for flexitarians, fish-eating population and the entire population were assessed. The incremental lifetime cancer risk (ILCR) estimates for the flexitarians, the entire population, and fish-eating population associated with dietary intake of these products ranged from 4.68 × 10−5 to 1.32 × 10−3, 1.06 × 10−3 to 2.97 × 10−2 and 1.46 × 10−3 to 4.12 × 10−2 respectively. Furthermore, the cancer risk of grilled and fried fish products assessed for the fish-eating population was compared with the cancer risk of raw fish calculated based on the peer-reviewed Indian literature. The mitigation strategies for reduction of PAHs and PCBs in defined fish products have been recommended in the study. The study also highlights the need for in-depth research on PAHs and PCBs formation in grilled and fried fish products.
{"title":"Fish consumption patterns and health risk assessment of polycyclic aromatic hydrocarbons and polychlorinated biphenyls in fried and grilled fish products and mitigation strategies","authors":"Abhishek ,&nbsp;S. Chakkaravarthi ,&nbsp;Tripti Agarwal","doi":"10.1016/j.toxrep.2025.101953","DOIUrl":"10.1016/j.toxrep.2025.101953","url":null,"abstract":"<div><div>In the present study, the concentration of 13PAHs and the six indicator PCBs was determined through GC-MS/MS in 36 grilled and fried fish products. The study is unique in terms of the simultaneous determination of two types of persistent organic pollutants in grilled and fried fish products. The concentration of ∑13PAHs and ∑6PCBs in these samples varied from 20.80 ± 2.06–947.65 ± 40.85 µg kg<sup>−1</sup> and 2.86 ± 0.16–46.52 ± 0.46 µg kg<sup>−1</sup>, respectively. Dietary exposure and human health risks due to the consumption of fried and grilled fish products for flexitarians, fish-eating population and the entire population were assessed. The incremental lifetime cancer risk (ILCR) estimates for the flexitarians, the entire population, and fish-eating population associated with dietary intake of these products ranged from 4.68 × 10<sup>−5</sup> to 1.32 × 10<sup>−3</sup>, 1.06 × 10<sup>−3</sup> to 2.97 × 10<sup>−2</sup> and 1.46 × 10<sup>−3</sup> to 4.12 × 10<sup>−2</sup> respectively. Furthermore, the cancer risk of grilled and fried fish products assessed for the fish-eating population was compared with the cancer risk of raw fish calculated based on the peer-reviewed Indian literature. The mitigation strategies for reduction of PAHs and PCBs in defined fish products have been recommended in the study. The study also highlights the need for in-depth research on PAHs and PCBs formation in grilled and fried fish products.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101953"},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143351135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development of therapeutic supplement using roasted-cashew-nut to protect cerebral vasoconstriction injury triggered by mixture of petroleum hydrocarbons in the hypothalamus and hippocampus of rat model
Q1 Environmental Science Pub Date : 2025-02-05 DOI: 10.1016/j.toxrep.2025.101943
J.K. Akintunde , V.O. Akomolafe , R.N. Ugbaja , A.M. Olude , A.D. Folayan
Petroleum-related activities have been a health global risk concern, particularly in the limbic disorders. The study aims to investigate the neuroprotection of roasted cashew nuts (RCN) on brain vasoconstriction injury induced by a mixture of petroleum hydrocarbons (MFPP). Seventy Male Wistar rats ranging 160 ± 10 g were randomized into seven groups. Group I was given distilled water. Group II was exposed to 0.2 ml MFPP. Group III, IV and V were exposed to 0.2 ml MFPP followed by treatment with 50 mg/kg atenolol, 10 % RCN and 20 % RCN, respectively. Group VI and VII were treated with 10 % RCN and 20 % RCN, respectively. The regimen period was 28 days. Cell pathological evaluation was done using hematoxylin and eosin staining and visualized under the microscope. Biochemical and molecular markers of brain vasoconstriction injury (BVI) were evaluated using spectrophotometer and RT-PCR analyzer, respectively. Student-T-test and one-way analysis of variance (ANOVA) were used to analyze the results. Sub-chronic exposure to MFPP induced BVI as evident in neuroinflammation and derangements in the histology of the hippocampus and hypothalamus coupled with momentous alterations in the neurons. Post treatment with RCN supplement remarkably modulated the effects by depleting the inflammatory mediators including HIF-1, p53 and MCP-1. Also, adenosinergic, purigenic and cholinergic of the hypothalamus and hippocampus were normalized by the supplement. It is pertinent to conclude that treatment with RCN inhibited BVI in rats via the NO-cAMP-PKA signaling pathway by reversing neuroinflammation, normalizing the purinergic and cholinergic neurotransmission in the hypothalamus and hippocampus, and stabilizing NO level coupled with brain histology improvement.
{"title":"Development of therapeutic supplement using roasted-cashew-nut to protect cerebral vasoconstriction injury triggered by mixture of petroleum hydrocarbons in the hypothalamus and hippocampus of rat model","authors":"J.K. Akintunde ,&nbsp;V.O. Akomolafe ,&nbsp;R.N. Ugbaja ,&nbsp;A.M. Olude ,&nbsp;A.D. Folayan","doi":"10.1016/j.toxrep.2025.101943","DOIUrl":"10.1016/j.toxrep.2025.101943","url":null,"abstract":"<div><div>Petroleum-related activities have been a health global risk concern, particularly in the limbic disorders. The study aims to investigate the neuroprotection of roasted cashew nuts (RCN) on brain vasoconstriction injury induced by a mixture of petroleum hydrocarbons (MFPP). Seventy Male Wistar rats ranging 160 ± 10 g were randomized into seven groups. Group I was given distilled water. Group II was exposed to 0.2 ml MFPP. Group III, IV and V were exposed to 0.2 ml MFPP followed by treatment with 50 mg/kg atenolol, 10 % RCN and 20 % RCN, respectively. Group VI and VII were treated with 10 % RCN and 20 % RCN, respectively. The regimen period was 28 days. Cell pathological evaluation was done using hematoxylin and eosin staining and visualized under the microscope. Biochemical and molecular markers of brain vasoconstriction injury (BVI) were evaluated using spectrophotometer and RT-PCR analyzer, respectively. Student-T-test and one-way analysis of variance (ANOVA) were used to analyze the results. Sub-chronic exposure to MFPP induced BVI as evident in neuroinflammation and derangements in the histology of the hippocampus and hypothalamus coupled with momentous alterations in the neurons. Post <sup>treatment with RCN supplement remarkably modulated the effects by depleting the</sup> inflammatory mediators including HIF-1, p53 and MCP-1. Also, adenosinergic, purigenic and cholinergic of the hypothalamus and hippocampus were normalized by the supplement. It is pertinent to conclude that treatment with RCN inhibited BVI in rats via the NO-cAMP-PKA signaling pathway by reversing neuroinflammation, normalizing the purinergic and cholinergic neurotransmission in the hypothalamus and hippocampus, and stabilizing NO level coupled with brain histology improvement.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101943"},"PeriodicalIF":0.0,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Equations for estimating binary mixture toxicity: Methyl-2-chloroacetoacetate-containing combinations
Q1 Environmental Science Pub Date : 2025-02-05 DOI: 10.1016/j.toxrep.2025.101939
Douglas A. Dawson , T. Wayne Schultz
Mixture toxicity was determined for 30 A+B combinations. Chemical A was the reactive soft electrophile methyl-2-chloroacetoacetate (M2CA), and chemical B was one of 30 reactive or non-reactive agents. Bioluminescence inhibition in Allovibrio fischeri was measured after 15-, 30-, and 45-minutes of exposure for A, B, and the mixture (MX) with ECx (i.e., EC25, EC50, and EC75) values being calculated. Concentration-response curves (CRCs) were developed for A and B at each exposure duration and used to create predicted CRCs for the concentration addition (CA) and independent action (IA) mixture toxicity models. Likewise, MX CRCs were generated and compared with model predictions, along with the calculation of additivity quotient (AQ) and independence quotient (IQ) values. Mixture toxicity vs. the models showed various combined effects, including toxicity that was slightly greater than IA and/or CA, consistency with CA, IA or both models, effects that were less toxic than expected for either model and antagonism. Simple linear regression analyses of time-dependent toxicity (TDT) data showed very strong correlations (r2 ≥ 0.997) for B-TDT vs. the average TDT for A and B. Likewise, for both CA and IA, multiple linear regression analyses showed strong correlations (r2 > 0.960) between MX ECx and either CA ECx and AQx or IA ECx and IQx values at each exposure duration. The results show that analyses of binary mixture toxicity data produced linear relationships resulting in equations that can effectively predict such toxicity.
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引用次数: 0
Understanding the impact of triazoles on female fertility and embryo development: Mechanisms and implications
Q1 Environmental Science Pub Date : 2025-02-04 DOI: 10.1016/j.toxrep.2025.101948
Sonal Sharma, Geeta Pandey
Triazoles are among the most widely used fungicides that were launched in 1980s and are one of the most important pesticide groups used in agriculture as plant growth regulators and stress protectors. Triazoles are also frequently used in the pharmaceutical industry to treat fungal and bacterial infections as well as to treat and prevent some forms of pneumonia. Humans are normally exposed to triazoles through food, water, and medications, which raises concerns about their potential adverse effects on health. Therefore, this review was planned to examine the impact of triazole fungicides on female fertility, as well as their teratogenic and embryotoxic effects. Various search engines such as PubMed, Google Scholar, Elsevier, IEEE were used to search the relevant articles published between 2006 and 2024 using the following keywords: "azoles," "female infertility," "reproductive toxicity," "teratogenicity," "triazoles," and "embryo toxicity." The findings suggest that triazoles might negatively affect female fertility and embryonic development through multiple mechanisms including inhibition or interference with key enzymes such as CYP17A1 and CYP19A1 (aromatase) involved in steroid hormone synthesis, endocrine disruption, oxidative stress, disruption of signaling pathways, and apoptosis. This review consolidates current knowledge on the teratogenic and embryotoxic properties of triazole fungicides, providing a comprehensive understanding of their health implications and addressing critical research gaps.
{"title":"Understanding the impact of triazoles on female fertility and embryo development: Mechanisms and implications","authors":"Sonal Sharma,&nbsp;Geeta Pandey","doi":"10.1016/j.toxrep.2025.101948","DOIUrl":"10.1016/j.toxrep.2025.101948","url":null,"abstract":"<div><div>Triazoles are among the most widely used fungicides that were launched in 1980s and are one of the most important pesticide groups used in agriculture as plant growth regulators and stress protectors. Triazoles are also frequently used in the pharmaceutical industry to treat fungal and bacterial infections as well as to treat and prevent some forms of pneumonia. Humans are normally exposed to triazoles through food, water, and medications, which raises concerns about their potential adverse effects on health. Therefore, this review was planned to examine the impact of triazole fungicides on female fertility, as well as their teratogenic and embryotoxic effects. Various search engines such as PubMed, Google Scholar, Elsevier, IEEE were used to search the relevant articles published between 2006 and 2024 using the following keywords: \"azoles,\" \"female infertility,\" \"reproductive toxicity,\" \"teratogenicity,\" \"triazoles,\" and \"embryo toxicity.\" The findings suggest that triazoles might negatively affect female fertility and embryonic development through multiple mechanisms including inhibition or interference with key enzymes such as CYP17A1 and CYP19A1 (aromatase) involved in steroid hormone synthesis, endocrine disruption, oxidative stress, disruption of signaling pathways, and apoptosis. This review consolidates current knowledge on the teratogenic and embryotoxic properties of triazole fungicides, providing a comprehensive understanding of their health implications and addressing critical research gaps.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101948"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
UHPLC-QTOF-MS/MS profiling, molecular networking, and molecular docking analysis of Gliricidia sepium (Jacq.) Kunth. ex. Walp. stem ethanolic extract and its gastroprotective effect on gastritis in rats
Q1 Environmental Science Pub Date : 2025-02-04 DOI: 10.1016/j.toxrep.2025.101944
Aya A. Wafaey , Seham S. El-Hawary , Osama G. Mohamed , Sahar S. Abdelrahman , Alaa M. Ali , Ahmed A. El-Rashedy , Mohamed F. Abdelhameed , Farid N. Kirollos
Metabolic profiling of the crude ethanolic extract of Gliricidia sepium (Jacq.) Kunth. ex. Walp. stem ethanolic extract (GSS) was conducted using ultra-high performance quadrupole time of flight mass spectrometry/mass spectrometry (UHPLC-QTOF-MS/MS) in negative mode, resulting in the identification of 23 compounds belonging to various classes such as flavonoids, fatty acids, triterpenoid saponins, and phenolic acids. Notably, eight flavonoids including kaempferol-3-O-robinoside-7-O-rhamnoside, isoquercitrin, kaempferol-3-O-rutinoside, apigenin-7-glucoside, kaempeferol-7-O-rhamnoside, luteolin, apigenin, and liquiritigenin, along with two phenolic acids (4-hydroxycinnamic acid and 2-hydroxyhydrocinnamic acid) and four triterpenoid saponins (soyasaponin I, soyasaponin II, soyasaponin III, and kaikasaponin III) were dereplicated. Additionally, nine fatty acid derivatives were identified, including azelaic acid and 2-isopropyl malic acid. Molecular networking analysis revealed the formation of clusters among compounds while others do not form clusters. Further analysis indicated that the GSS ethanolic extract exhibited a total phenolic content of 38.78 ± 1.609 µg of gallic acid equivalent/mg and a total flavonoid content of 5.62 ± 0.50 µg of rutin equivalent/mg. Biological evaluations showed that GSS ethanolic extract mitigated gastric tissue injury induced by pyloric ligation, with a notable reduction in oxidative stress marker reactive oxygen species levels and inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha levels. Additionally, it enhanced superoxide dismutase and inhibitor of nuclear factor kappa B alpha levels, while lowering the expression of inducible nitric oxide synthase. Histopathological examination revealed significant improvements in gastric tissue morphology in GSS-treated groups compared to the control group. Molecular docking studies indicated potential interactions between GSS ethanolic extract compounds and various target proteins involved in oxidative stress, inflammation, and gastric protection in gastritis. This study aims to investigate the potential gastroprotective activity of GSS ethanolic extract against gastritis induced via pyloric ligation.
{"title":"UHPLC-QTOF-MS/MS profiling, molecular networking, and molecular docking analysis of Gliricidia sepium (Jacq.) Kunth. ex. Walp. stem ethanolic extract and its gastroprotective effect on gastritis in rats","authors":"Aya A. Wafaey ,&nbsp;Seham S. El-Hawary ,&nbsp;Osama G. Mohamed ,&nbsp;Sahar S. Abdelrahman ,&nbsp;Alaa M. Ali ,&nbsp;Ahmed A. El-Rashedy ,&nbsp;Mohamed F. Abdelhameed ,&nbsp;Farid N. Kirollos","doi":"10.1016/j.toxrep.2025.101944","DOIUrl":"10.1016/j.toxrep.2025.101944","url":null,"abstract":"<div><div>Metabolic profiling of the crude ethanolic extract of <em>Gliricidia sepium</em> (Jacq.) Kunth. ex. Walp. stem ethanolic extract (GSS) was conducted using ultra-high performance quadrupole time of flight mass spectrometry/mass spectrometry (UHPLC-QTOF-MS/MS) in negative mode, resulting in the identification of 23 compounds belonging to various classes such as flavonoids, fatty acids, triterpenoid saponins, and phenolic acids. Notably, eight flavonoids including kaempferol-3-<em>O</em>-robinoside-7-<em>O</em>-rhamnoside, isoquercitrin, kaempferol-3-<em>O</em>-rutinoside, apigenin-7-glucoside, kaempeferol-7-<em>O</em>-rhamnoside, luteolin, apigenin, and liquiritigenin, along with two phenolic acids (4-hydroxycinnamic acid and 2-hydroxyhydrocinnamic acid) and four triterpenoid saponins (soyasaponin I, soyasaponin II, soyasaponin III, and kaikasaponin III) were dereplicated. Additionally, nine fatty acid derivatives were identified, including azelaic acid and 2-isopropyl malic acid. Molecular networking analysis revealed the formation of clusters among compounds while others do not form clusters. Further analysis indicated that the GSS ethanolic extract exhibited a total phenolic content of 38.78 ± 1.609 µg of gallic acid equivalent/mg and a total flavonoid content of 5.62 ± 0.50 µg of rutin equivalent/mg. Biological evaluations showed that GSS ethanolic extract mitigated gastric tissue injury induced by pyloric ligation, with a notable reduction in oxidative stress marker reactive oxygen species levels and inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha levels. Additionally, it enhanced superoxide dismutase and inhibitor of nuclear factor kappa B alpha levels, while lowering the expression of inducible nitric oxide synthase. Histopathological examination revealed significant improvements in gastric tissue morphology in GSS-treated groups compared to the control group. Molecular docking studies indicated potential interactions between GSS ethanolic extract compounds and various target proteins involved in oxidative stress, inflammation, and gastric protection in gastritis. This study aims to investigate the potential gastroprotective activity of GSS ethanolic extract against gastritis induced via pyloric ligation.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"Article 101944"},"PeriodicalIF":0.0,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Toxicology Reports
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