The study examines the health of petroleum industry employees in Basrah City, southern Iraq, with a focus on their exposure to toxic chemicals, specifically the impact of oxidative stress on their hearts. This study included two groups of men: in the first group, ninety employees were exposed to crude oil well sites in Basrah, and ninety individuals were in the control group. This study evaluated two ultra-fine particles in the participants' blood: the polycyclic aromatic hydrocarbon metabolite [Benzopyrene diol epoxide (BPDE)] level and the toxic cadmium. The study also aimed to evaluate the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the serum of the study participants and monitor the lipid profile. The results showed high levels of BPDE, a high concentration of cadmium in the blood, increased lipid peroxidation, and decreased SOD in the exposed group compared to the control group. The results also showed a significant increase in triglycerides. The increase in reactive oxygen species production is a major risk factor for atherosclerosis, and high triglycerides indicate artery wall deposits, leading to cardiovascular disease.
{"title":"Clinical study on the relationship between exposure to ultrafine particles (PM0.1) and cardiovascular diseases in petroleum workers","authors":"Nagham Jawad Kadam AL-Lami , Nadhum A.N. Awad , Saad Shaheen Hamadi Al-Taher","doi":"10.1016/j.toxrep.2025.102119","DOIUrl":"10.1016/j.toxrep.2025.102119","url":null,"abstract":"<div><div>The study examines the health of petroleum industry employees in Basrah City, southern Iraq, with a focus on their exposure to toxic chemicals, specifically the impact of oxidative stress on their hearts. This study included two groups of men: in the first group, ninety employees were exposed to crude oil well sites in Basrah, and ninety individuals were in the control group. This study evaluated two ultra-fine particles in the participants' blood: the polycyclic aromatic hydrocarbon metabolite [Benzopyrene diol epoxide (BPDE)] level and the toxic cadmium. The study also aimed to evaluate the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the serum of the study participants and monitor the lipid profile. The results showed high levels of BPDE, a high concentration of cadmium in the blood, increased lipid peroxidation, and decreased SOD in the exposed group compared to the control group. The results also showed a significant increase in triglycerides. The increase in reactive oxygen species production is a major risk factor for atherosclerosis, and high triglycerides indicate artery wall deposits, leading to cardiovascular disease.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102119"},"PeriodicalIF":0.0,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cholestasis is a reduction or cessation of bile flow in the biliary system, which can be life-threatening. Dimethyl Fumarate could induce anti-inflammatory and antioxidant effects in the body.
Objective
This investigation focused on assessing the impact of Dimethyl Fumarate on liver levels of transforming growth factor beta (TGF-β) to mitigate biochemical, histopathological, and immunohistochemical alterations in cholestasis-induced rat models.
Methods
Forty male adult Wistar rats were divided into eight groups (healthy control treated with distilled water, healthy rats treated with 50, 100, and 200 mg/kg of Dimethyl Fumarate, bile duct ligation (BDL), and experiment BDL groups were treated with 50, 100, and 200 mg/kg of Dimethyl Fumarate). After the gavage treatment period of 45 days, the rats were anesthetized and underwent blood sampling. Liver damage was assessed by measuring hepatic marker enzymes (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin), histopathological (lesion assessment), and immunohistochemical (TGF-β expression level) observation.
Results
The findings demonstrated that administration of varying doses of Dimethyl Fumarate via gavage led to a statistically significant reduction in serum concentrations of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin (P < 0.05). The optimal dosage identified was 200 mg/kg of Dimethyl Fumarate. Furthermore, the data indicated that gavage treatment with Dimethyl Fumarate significantly attenuated TGF-β expression level and mitigated hepatic damage (P < 0.05).
Conclusion
This strategy may reduce inflammation, cholestasis, and fibrosis outcomes, attributed to its anti-inflammatory and antioxidant properties. Nonetheless, further research is necessary to substantiate these findings.
{"title":"Evaluation of the effects of dimethyl fumarate on transforming growth factor beta levels in the liver of rats with bile duct ligation-induced cholestasis","authors":"Hannaneh Vossoughi , Pejman Mortazavi , Mahsa Ale-Ebrahim , Razieh Hosseini","doi":"10.1016/j.toxrep.2025.102115","DOIUrl":"10.1016/j.toxrep.2025.102115","url":null,"abstract":"<div><h3>Background</h3><div>Cholestasis is a reduction or cessation of bile flow in the biliary system, which can be life-threatening. Dimethyl Fumarate could induce anti-inflammatory and antioxidant effects in the body.</div></div><div><h3>Objective</h3><div>This investigation focused on assessing the impact of Dimethyl Fumarate on liver levels of transforming growth factor beta (TGF-β) to mitigate biochemical, histopathological, and immunohistochemical alterations in cholestasis-induced rat models.</div></div><div><h3>Methods</h3><div>Forty male adult Wistar rats were divided into eight groups (healthy control treated with distilled water, healthy rats treated with 50, 100, and 200 mg/kg of Dimethyl Fumarate, bile duct ligation (BDL), and experiment BDL groups were treated with 50, 100, and 200 mg/kg of Dimethyl Fumarate). After the gavage treatment period of 45 days, the rats were anesthetized and underwent blood sampling. Liver damage was assessed by measuring hepatic marker enzymes (alanine transaminase, aspartate transaminase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin), histopathological (lesion assessment), and immunohistochemical (TGF-β expression level) observation.</div></div><div><h3>Results</h3><div>The findings demonstrated that administration of varying doses of Dimethyl Fumarate via gavage led to a statistically significant reduction in serum concentrations of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transferase, and total bilirubin (<em>P</em> < 0.05). The optimal dosage identified was 200 mg/kg of Dimethyl Fumarate. Furthermore, the data indicated that gavage treatment with Dimethyl Fumarate significantly attenuated TGF-β expression level and mitigated hepatic damage (<em>P</em> < 0.05).</div></div><div><h3>Conclusion</h3><div>This strategy may reduce inflammation, cholestasis, and fibrosis outcomes, attributed to its anti-inflammatory and antioxidant properties. Nonetheless, further research is necessary to substantiate these findings.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102115"},"PeriodicalIF":0.0,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zebrafish embryos are widely used in developmental toxicity testing. However, the extent to which genetic background influences susceptibility to teratogenic compounds remains incompletely understood. We here evaluated inter-strain variability in both phenotypic and transcriptomic responses to six model teratogens using five commonly utilized zebrafish strains, AB, TU, RW, WIK, and PET. All test compounds, valproic acid, hydroxyurea, methotrexate, acitretin, topiramate, and ibuprofen, elicited concentration-dependent developmental toxicity characterized by malformations at moderate doses and lethality at higher concentrations. Despite distinct toxicodynamic profiles, the incidence and severity of phenotypic outcomes were highly consistent across strains. Transcriptomic analysis was performed following exposure to valproic acid, hydroxyurea, and warfarin, revealing strong, dose-dependent gene expression changes that were largely conserved among strains. Principal component analysis demonstrated that chemical concentration, rather than strain, was the dominant driver of transcriptional variation. Minor strain-specific differences were observed at baseline or low-dose levels but did not alter the overall direction or magnitude of response. These findings demonstrate that zebrafish embryos from diverse genetic backgrounds exhibit broadly conserved developmental and molecular responses to teratogens. The minimal inter-strain variability supports the use of any wild-type strain, transgenic line, or even outbred population in developmental toxicity testing without compromising sensitivity or reproducibility. Our study reinforces the suitability of zebrafish as a robust vertebrate model in regulatory toxicology.
{"title":"Comparative analysis of teratogen-induced malformations and gene expression across zebrafish strains in early development","authors":"Chitose Taya , Kota Ujibe , Shinnosuke Shimodaira , Aoto Sakamoto , Seiji Wada , Makoto Kashima , Hiromi Hirata","doi":"10.1016/j.toxrep.2025.102117","DOIUrl":"10.1016/j.toxrep.2025.102117","url":null,"abstract":"<div><div>Zebrafish embryos are widely used in developmental toxicity testing. However, the extent to which genetic background influences susceptibility to teratogenic compounds remains incompletely understood. We here evaluated inter-strain variability in both phenotypic and transcriptomic responses to six model teratogens using five commonly utilized zebrafish strains, AB, TU, RW, WIK, and PET. All test compounds, valproic acid, hydroxyurea, methotrexate, acitretin, topiramate, and ibuprofen, elicited concentration-dependent developmental toxicity characterized by malformations at moderate doses and lethality at higher concentrations. Despite distinct toxicodynamic profiles, the incidence and severity of phenotypic outcomes were highly consistent across strains. Transcriptomic analysis was performed following exposure to valproic acid, hydroxyurea, and warfarin, revealing strong, dose-dependent gene expression changes that were largely conserved among strains. Principal component analysis demonstrated that chemical concentration, rather than strain, was the dominant driver of transcriptional variation. Minor strain-specific differences were observed at baseline or low-dose levels but did not alter the overall direction or magnitude of response. These findings demonstrate that zebrafish embryos from diverse genetic backgrounds exhibit broadly conserved developmental and molecular responses to teratogens. The minimal inter-strain variability supports the use of any wild-type strain, transgenic line, or even outbred population in developmental toxicity testing without compromising sensitivity or reproducibility. Our study reinforces the suitability of zebrafish as a robust vertebrate model in regulatory toxicology.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102117"},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-21DOI: 10.1016/j.toxrep.2025.102116
Justin Atiang Beshel , Samuel Usoh Ukweni , Idara Asuquo Okon , Daniel Udofia Owu
Naringenin, a major flavonoid in oranges, grapefruit, tomato skin and apocynin a polyphenolic compound isolated from plants, such as Apocynum cannabinum are known to possess anti-oxidant, anti-inflammatory, and anti-cancer properties. Doxorubicin (DOX) is an antibiotic, effective in the treatment of cancer, but notorious for its propensity to cause cardiotoxicity. This study investigated the combined effects of naringenin and apocynin in DOX-induced cardiac toxicity. Thirty rats were randomly divided into five groups (n = 6) as follows: Normal Control (NC), DOX only, DOX+ naringenin, DOX + apocynin and DOX +naringenin + apocynin. DOX (2.5 mg/kg) was administered intraperitoneally, three times per week for two weeks (cumulative dose of 15 mg/kg). Naringenin (50 mg/kg/day) and apocynin (25 mg/kg/day) were administered orally. ECG measurements were carried out and heart homogenates were used to estimate cardiac inflammatory (IL-6, CRP), cardiac toxicity (CTnT, LDH, CKMB) and hypertensive (NO, ACE) markers. Histopathological examination of the heart was performed. Doxorubicin significantly altered the ECG with large T-wave, ST-elevation and wide QRS-complex. Results also showed significant changes in cardiac inflammatory and hypertensive biomarkers. Naringenin and apocynin treatment significantly attenuated the impact of doxorubicin on rats ECG, decreased biomarkers levels of cardiac inflammatory and hypertensive biomarkers. The cytoarchitecture of heart significantly improved in naringenin and apocynin treated groups, when compared to DOX only group. This study indicates that administration of naringenin and apocynin have cardioprotective ability and also ameliorated cardiotoxicity-induced by doxorubicin probably due to its anti-inflammatory and free radical scavenging properties.
{"title":"Is the use of anthracyclines implicated in myocardial injury? Investigating the cardio modulatory effects of naringenin and apocynin in doxorubicin-induced cardiotoxicity in rats","authors":"Justin Atiang Beshel , Samuel Usoh Ukweni , Idara Asuquo Okon , Daniel Udofia Owu","doi":"10.1016/j.toxrep.2025.102116","DOIUrl":"10.1016/j.toxrep.2025.102116","url":null,"abstract":"<div><div>Naringenin, a major flavonoid in oranges, grapefruit, tomato skin and apocynin a polyphenolic compound isolated from plants, such as <em>Apocynum cannabinum</em> are known to possess anti-oxidant, anti-inflammatory, and anti-cancer properties. Doxorubicin (DOX) is an antibiotic, effective in the treatment of cancer, but notorious for its propensity to cause cardiotoxicity. This study investigated the combined effects of naringenin and apocynin in DOX-induced cardiac toxicity. Thirty rats were randomly divided into five groups (n = 6) as follows: Normal Control (NC), DOX only, DOX+ naringenin, DOX + apocynin and DOX +naringenin + apocynin. DOX (2.5 mg/kg) was administered intraperitoneally, three times per week for two weeks (cumulative dose of 15 mg/kg). Naringenin (50 mg/kg/day) and apocynin (25 mg/kg/day) were administered orally. ECG measurements were carried out and heart homogenates were used to estimate cardiac inflammatory (IL-6, CRP), cardiac toxicity (CTnT, LDH, CKMB) and hypertensive (NO, ACE) markers. Histopathological examination of the heart was performed. Doxorubicin significantly altered the ECG with large T-wave, ST-elevation and wide QRS-complex. Results also showed significant changes in cardiac inflammatory and hypertensive biomarkers. Naringenin and apocynin treatment significantly attenuated the impact of doxorubicin on rats ECG, decreased biomarkers levels of cardiac inflammatory and hypertensive biomarkers. The cytoarchitecture of heart significantly improved in naringenin and apocynin treated groups, when compared to DOX only group. This study indicates that administration of naringenin and apocynin have cardioprotective ability and also ameliorated cardiotoxicity-induced by doxorubicin probably due to its anti-inflammatory and free radical scavenging properties.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102116"},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Traditional Tobacco smoking (TTS) is globally known as the single largest avoidable risk factor for a broad range of diseases. Over a century ago, there has been a wide spread of tobacco cigarettes, originating particularly from the Americas; and most recently alternative tobacco products, such as e-cigarettes aerosol (ECA) and smokeless tobacco. This is due to the perceived safety of the latter. There are several indications that frequent e-cigarette use causes possible direct and indirect health threats, requiring urgent regulatory provisions particularly in resource constrain setting. Data for this review were gotten through a rigorous search of scientific literatures on PubMed, Elsevier, Google scholar and Scopus. The deleterious health effects of ECA have been linked largely to the e-juice or e-liquid which majorly contains nicotine, flavorings, propylene glycol and other unregulated additives. In the respiratory system, TTS and ECA cause increase in pulmonary macrophage count and higher cell influx. However, TTS caused a higher lipid peroxidation, while ECA caused a negative shift in the histology of the lungs, featuring an increase in volume density of the alveolar space. Studies involving the cardiovascular system explored the constituents such as nicotine, linked to atherosclerosis; cardiac tissue remodeling and cardiotoxic thermal metabolites of propylene glycol. On cardiac tissue remodeling, ECA caused significant increase in angiogenesis in mouse heart tissues, coupled with increase collagen production but not tissue fibrosis. This suggests that acute exposure to ECA did not adversely affect contractile functions or fibrosis. However, this was contrary with TTS, which showed inhibition of angiogenesis and induction of cardiac fibrosis. The increasing use of ECA amongst young adults showed more tendency for neurological defects when compared with TTS, this is mainly due to combinatory neurotoxic effects of nicotine, flavorings, formaldehyde, etc., causing a negative effect on cognition and attention span.
Putting these together, Uncontrolled spreading of these unregulated and addictive products is creating inconsistent quality assurance in resource constrain countries resulting in public health risk. There is therefore an urgent need for the regulation of these products and further research carried out on long-term safety of e-cigarettes, while national health regulators and policy makers should provide informed policies on the use of e-cigarettes and other alternative tobacco products.
{"title":"COMPARATIVE EFFECTS OF ALTERNATE TOBACCO PRODUCT (ELECTRONIC CIGARETTE) AND TRADITIONAL TOBACCO SMOKING ON VARIOUS ORGAN/SYSTEMS: A GUIDE TO REGULATORS AND HEALTH POLICY MAKERS.","authors":"Saheed Olanrewaju Afolabi , Solomon Olagoke Olaoye , Nyamgee Amase , Anoka Ayembe Njan","doi":"10.1016/j.toxrep.2025.102100","DOIUrl":"10.1016/j.toxrep.2025.102100","url":null,"abstract":"<div><div>Traditional Tobacco smoking (TTS) is globally known as the single largest avoidable risk factor for a broad range of diseases. Over a century ago, there has been a wide spread of tobacco cigarettes, originating particularly from the Americas; and most recently alternative tobacco products, such as e-cigarettes aerosol (ECA) and smokeless tobacco. This is due to the perceived safety of the latter. There are several indications that frequent e-cigarette use causes possible direct and indirect health threats, requiring urgent regulatory provisions particularly in resource constrain setting. Data for this review were gotten through a rigorous search of scientific literatures on PubMed, Elsevier, Google scholar and Scopus. The deleterious health effects of ECA have been linked largely to the e-juice or e-liquid which majorly contains nicotine, flavorings, propylene glycol and other unregulated additives. In the respiratory system, TTS and ECA cause increase in pulmonary macrophage count and higher cell influx. However, TTS caused a higher lipid peroxidation, while ECA caused a negative shift in the histology of the lungs, featuring an increase in volume density of the alveolar space. Studies involving the cardiovascular system explored the constituents such as nicotine, linked to atherosclerosis; cardiac tissue remodeling and cardiotoxic thermal metabolites of propylene glycol. On cardiac tissue remodeling, ECA caused significant increase in angiogenesis in mouse heart tissues, coupled with increase collagen production but not tissue fibrosis. This suggests that acute exposure to ECA did not adversely affect contractile functions or fibrosis. However, this was contrary with TTS, which showed inhibition of angiogenesis and induction of cardiac fibrosis. The increasing use of ECA amongst young adults showed more tendency for neurological defects when compared with TTS, this is mainly due to combinatory neurotoxic effects of nicotine, flavorings, formaldehyde, etc., causing a negative effect on cognition and attention span.</div><div>Putting these together, Uncontrolled spreading of these unregulated and addictive products is creating inconsistent quality assurance in resource constrain countries resulting in public health risk. There is therefore an urgent need for the regulation of these products and further research carried out on long-term safety of e-cigarettes, while national health regulators and policy makers should provide informed policies on the use of e-cigarettes and other alternative tobacco products.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102100"},"PeriodicalIF":0.0,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-16DOI: 10.1016/j.toxrep.2025.102114
Elsa Sandeno , Sergey Karachenets , Kourtney Zehlke , Raza Khan , Michael Kalinoski , Pravin Meshram , James V. Harmon Jr.
A 40-year-old man presented to the emergency department within 6 h of a massive overdose of 500 units of long-acting feline glargine insulin intravenously and an estimated 50 mg of clozapine. Upon initial assessment, his Glasgow Coma Scale (GCS) was 15 and his blood sugar level was 45 mg/dL. The patient was successfully managed with dextrose infusions and close monitoring of blood sugar and electrolytes. To date, no cases have been documented in the literature describing an overdose of insulin formulation intended for veterinary use. Cases of overdose with animal-prescribed human insulin analogs can be managed similarly to previously reported cases of human insulin overdose.
{"title":"Survival following intentional overdose of veterinary insulin: A case report","authors":"Elsa Sandeno , Sergey Karachenets , Kourtney Zehlke , Raza Khan , Michael Kalinoski , Pravin Meshram , James V. Harmon Jr.","doi":"10.1016/j.toxrep.2025.102114","DOIUrl":"10.1016/j.toxrep.2025.102114","url":null,"abstract":"<div><div>A 40-year-old man presented to the emergency department within 6 h of a massive overdose of 500 units of long-acting feline glargine insulin intravenously and an estimated 50 mg of clozapine. Upon initial assessment, his Glasgow Coma Scale (GCS) was 15 and his blood sugar level was 45 mg/dL. The patient was successfully managed with dextrose infusions and close monitoring of blood sugar and electrolytes. To date, no cases have been documented in the literature describing an overdose of insulin formulation intended for veterinary use. Cases of overdose with animal-prescribed human insulin analogs can be managed similarly to previously reported cases of human insulin overdose.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102114"},"PeriodicalIF":0.0,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144889039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-15DOI: 10.1016/j.toxrep.2025.102113
Daniel Itiza Akaahan , Augustine Uche Agu , Nkemjika Chinyere Anyanwu , Vivian Onyinye Orjiako , Godson Emeka Anyanwu
Background
Methylparaben is a commonly used preservative in the cosmetics, pharmaceutical, and food industries, valued for its antibacterial and antifungal effects. Numerous in vitro and in vivo studies have investigated its adverse effects on sperm count, testosterone levels, and reproductive organ weight. Baicalin, which comes from the dried roots of the plant Scutellaria baicalensis Georgi, is a natural compound that may have various health benefits, such as reducing fibrosis, itching, bacteria, oxidative stress, inflammation, and cancer. This study investigated the effect of baicalin on the changes in male reproductive hormones and enzyme activity brought about by methylparaben.
Method
A total of forty-five adult male Wistar rats were randomly allocated into nine distinct groups, each comprising five rats. Over a period of 28 days, these subjects were administered treatments via gastric gavage, which included distilled water, peanut oil, methylparaben, or differing doses of baicalin, either in isolation or in conjunction with methylparaben. Post-treatment, blood samples were obtained under terminal anesthesia for the purpose of serum analysis. Assays for hormonal levels (FSH, LH, testosterone) and enzymatic activity (17β-HSD3) were performed utilising ELISA and spectrophotometric techniques in accordance with established protocols.
Results
Rats treated with methylparaben (Group 3) had much lower levels of FSH, LH, testosterone, and 17β-HSD compared to the other groups, and baicalin was able to reduce these effects in a dose-dependent manner. Higher baicalin doses restored hormone and enzyme levels to near-control values levels indicating its protective benefits.
Conclusion
The results indicate that baicalin could mitigate the reproductive toxicity induced by methylparaben, owing to its antioxidant and regulatory characteristics, highlighting its potential as a protective agent against endocrine-disrupting chemicals
{"title":"Protective role of baicalin against methylparaben-induced reproductive toxicity: Insights into hormonal and enzymatic regulation","authors":"Daniel Itiza Akaahan , Augustine Uche Agu , Nkemjika Chinyere Anyanwu , Vivian Onyinye Orjiako , Godson Emeka Anyanwu","doi":"10.1016/j.toxrep.2025.102113","DOIUrl":"10.1016/j.toxrep.2025.102113","url":null,"abstract":"<div><h3>Background</h3><div>Methylparaben is a commonly used preservative in the cosmetics, pharmaceutical, and food industries, valued for its antibacterial and antifungal effects. Numerous in vitro and in vivo studies have investigated its adverse effects on sperm count, testosterone levels, and reproductive organ weight. Baicalin, which comes from the dried roots of the plant Scutellaria baicalensis Georgi, is a natural compound that may have various health benefits, such as reducing fibrosis, itching, bacteria, oxidative stress, inflammation, and cancer. This study investigated the effect of baicalin on the changes in male reproductive hormones and enzyme activity brought about by methylparaben.</div></div><div><h3>Method</h3><div>A total of forty-five adult male Wistar rats were randomly allocated into nine distinct groups, each comprising five rats. Over a period of 28 days, these subjects were administered treatments via gastric gavage, which included distilled water, peanut oil, methylparaben, or differing doses of baicalin, either in isolation or in conjunction with methylparaben. Post-treatment, blood samples were obtained under terminal anesthesia for the purpose of serum analysis. Assays for hormonal levels (FSH, LH, testosterone) and enzymatic activity (17β-HSD3) were performed utilising ELISA and spectrophotometric techniques in accordance with established protocols.</div></div><div><h3>Results</h3><div>Rats treated with methylparaben (Group 3) had much lower levels of FSH, LH, testosterone, and 17β-HSD compared to the other groups, and baicalin was able to reduce these effects in a dose-dependent manner. Higher baicalin doses restored hormone and enzyme levels to near-control values levels indicating its protective benefits.</div></div><div><h3>Conclusion</h3><div>The results indicate that baicalin could mitigate the reproductive toxicity induced by methylparaben, owing to its antioxidant and regulatory characteristics, highlighting its potential as a protective agent against endocrine-disrupting chemicals</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102113"},"PeriodicalIF":0.0,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-13DOI: 10.1016/j.toxrep.2025.102112
Anna S. van Wyk , Olusesan Ojo, Olusola Bodede, Gerhard Prinsloo
Herbal products are widely used in healthcare due to their therapeutic potential. However, concerns persist among medicinal chemists and regulatory toxicologists regarding their safety and potential toxicity. Botanical products used in herbal formulations requires rigorous risk assessments. In this study, we applied in silico toxicity testing using natural flavouring complexes (NFCs) approach and Toxtree® v3.1.0 software to assess toxicological risk associated with Curtisia dentata, a widely used medicinal plant for treating diseases. We first conducted experimental analysis of the hexane crude extract of C. dentata using gas chromatography–mass spectrometry (GC-MS) to identify its chemical constituents. A total of 124 compounds were identified from GC-MS analysis and verified using reputable databases, including PubChem, Human Metabolome Database (HMDB), National Institute of Standards and Technology (NIST) database, and scientific literature. The Cramer’s toxicity class of the identified components was determined based on their congeneric groups. The identified constituents were then subjected to in silico toxicity evaluation using Toxtree® v3.1.0. Certain constituents, including aniline, 2,6-dimethoxybenzoquinone, and 1-iodododecane triggered structural alerts for genotoxic carcinogenicity and mutagenicity, while phthalic acid, 4-chloro-3-methylphenyl undecyl ester exhibited alerts for non-genotoxic carcinogenicity. While C. dentata has undoubted proven pharmacological effects, further studies should focus on confirming the in silico predictions through targeted in vitro and in vivo studies, particularly for constituents that fired multiple structural alerts.
{"title":"In silico toxicological risk assessment of chemical constituents from Curtisia dentata stem-bark extract","authors":"Anna S. van Wyk , Olusesan Ojo, Olusola Bodede, Gerhard Prinsloo","doi":"10.1016/j.toxrep.2025.102112","DOIUrl":"10.1016/j.toxrep.2025.102112","url":null,"abstract":"<div><div>Herbal products are widely used in healthcare due to their therapeutic potential. However, concerns persist among medicinal chemists and regulatory toxicologists regarding their safety and potential toxicity. Botanical products used in herbal formulations requires rigorous risk assessments. In this study, we applied <em>in silico</em> toxicity testing using natural flavouring complexes (NFCs) approach and Toxtree® v3.1.0 software to assess toxicological risk associated with <em>Curtisia dentata</em>, a widely used medicinal plant for treating diseases. We first conducted experimental analysis of the hexane crude extract of <em>C. dentata</em> using gas chromatography–mass spectrometry (GC-MS) to identify its chemical constituents. A total of 124 compounds were identified from GC-MS analysis and verified using reputable databases, including PubChem, Human Metabolome Database (HMDB), National Institute of Standards and Technology (NIST) database, and scientific literature. The Cramer’s toxicity class of the identified components was determined based on their congeneric groups. The identified constituents were then subjected to in silico toxicity evaluation using Toxtree® v3.1.0. Certain constituents, including aniline, 2,6-dimethoxybenzoquinone, and 1-iodododecane triggered structural alerts for genotoxic carcinogenicity and mutagenicity, while phthalic acid, 4-chloro-3-methylphenyl undecyl ester exhibited alerts for non-genotoxic carcinogenicity. While <em>C. dentata</em> has undoubted proven pharmacological effects, further studies should focus on confirming the <em>in silico</em> predictions through targeted <em>in vitro</em> and <em>in vivo</em> studies, particularly for constituents that fired multiple structural alerts.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102112"},"PeriodicalIF":0.0,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144840833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-11DOI: 10.1016/j.toxrep.2025.102111
Wonkyun Jung , Mi-Jin Yang , Min-Sung Kang , Jin-Bae Kim , Kyung-Sik Yoon , Taekyung Yu , Cheolho Yoon , Hae Won Yang , Seong-Jin Choi , Eun-Jung Park
Given the expected increase in exposure to airborne microplastics, we here aimed to assess the acute and subchronic toxicity of inhaled polyethylene microplastics (PE-MPs). At 24 h post-exposure (0, 125, 250, and 500 μg/lung), PE-MPs were found within alveolar macrophages in the lungs of PE-MP-treated mice, along with an increase in the total number of pulmonary cells and higher pulmonary levels of LDH, CXCL-1, and CCL-2. Similarly, when exposed twice for 14 days (weekly, 0, 125, 250, and 500 μg/lung), the total number of pulmonary cells and the levels of pulmonary chemokines and blood IgE were elevated, whereas the expression of surface proteins related to cell-to-cell interactions was inhibited on the pulmonary cells of mice exposed to PE-MPs. After 90 days of repeated intratracheal instillation (0, 5, 25, and 50 μg/lung), PE-MPs deposited in the lung tissues and increased dose-dependently both the total number of pulmonary cells and inflammatory cytokine levels. Furthermore, infiltration of inflammatory cells, formation of multinucleated giant cells, and thickening of the alveolar wall were noted in the lung tissues of PE-MP-treated male and female mice. While the production of IgA and IgG was inhibited in male and female mice following exposure to PE-MPs, the levels of IgE and IgM tended to increase. In addition, the expression of fibrillar collagens was enhanced in the lung tissues of PE-MP-treated mice. Taken together, we suggest that chronic pulmonary exposure to PE-MPs may cause immune dysregulation by impairing the antigen-presenting function of alveolar macrophages and that PE-MP-induced chronic inflammation may be linked to fibrotic lesions. In addition, we believe that these hypotheses will be clarified by further study of the effects of chronic exposure to PE-MPs on lung function.
{"title":"Chronic lung tissue deposition of inhaled polyethylene microplastics may lead to fibrotic lesions","authors":"Wonkyun Jung , Mi-Jin Yang , Min-Sung Kang , Jin-Bae Kim , Kyung-Sik Yoon , Taekyung Yu , Cheolho Yoon , Hae Won Yang , Seong-Jin Choi , Eun-Jung Park","doi":"10.1016/j.toxrep.2025.102111","DOIUrl":"10.1016/j.toxrep.2025.102111","url":null,"abstract":"<div><div>Given the expected increase in exposure to airborne microplastics, we here aimed to assess the acute and subchronic toxicity of inhaled polyethylene microplastics (PE-MPs). At 24 h post-exposure (0, 125, 250, and 500 μg/lung), PE-MPs were found within alveolar macrophages in the lungs of PE-MP-treated mice, along with an increase in the total number of pulmonary cells and higher pulmonary levels of LDH, CXCL-1, and CCL-2. Similarly, when exposed twice for 14 days (weekly, 0, 125, 250, and 500 μg/lung), the total number of pulmonary cells and the levels of pulmonary chemokines and blood IgE were elevated, whereas the expression of surface proteins related to cell-to-cell interactions was inhibited on the pulmonary cells of mice exposed to PE-MPs. After 90 days of repeated intratracheal instillation (0, 5, 25, and 50 μg/lung), PE-MPs deposited in the lung tissues and increased dose-dependently both the total number of pulmonary cells and inflammatory cytokine levels. Furthermore, infiltration of inflammatory cells, formation of multinucleated giant cells, and thickening of the alveolar wall were noted in the lung tissues of PE-MP-treated male and female mice. While the production of IgA and IgG was inhibited in male and female mice following exposure to PE-MPs, the levels of IgE and IgM tended to increase. In addition, the expression of fibrillar collagens was enhanced in the lung tissues of PE-MP-treated mice. Taken together, we suggest that chronic pulmonary exposure to PE-MPs may cause immune dysregulation by impairing the antigen-presenting function of alveolar macrophages and that PE-MP-induced chronic inflammation may be linked to fibrotic lesions. In addition, we believe that these hypotheses will be clarified by further study of the effects of chronic exposure to PE-MPs on lung function.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102111"},"PeriodicalIF":0.0,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Methotrexate (MTX) is a commonly used antimetabolite for managing various autoimmune disorders and cancers. While it is generally well-tolerated at low doses, certain factors may predispose patients to significant toxicity. Here we present a case of 49-year-old male with advanced buccal mucosa squamous cell carcinoma who developed acute severe cutaneous toxicity following low dose of intravenous MTX therapy. After receiving two weekly doses, the patient experienced grade 4 oral mucositis and multiple erythematous plaques. This case highlights the importance of early recognition and prompt management of MTX toxicity, even at low doses, particularly in patients with risk factors such as prior antibiotic use and low serum albumin levels.
{"title":"Acute cutaneous adverse effects of methotrexate: A case report highlighting therapeutic challenges","authors":"Saarthak Miglani, Tanshi Daljit, Anurita Srivastava, Arun Kumar Rathi","doi":"10.1016/j.toxrep.2025.102108","DOIUrl":"10.1016/j.toxrep.2025.102108","url":null,"abstract":"<div><div>Methotrexate (MTX) is a commonly used antimetabolite for managing various autoimmune disorders and cancers. While it is generally well-tolerated at low doses, certain factors may predispose patients to significant toxicity. Here we present a case of 49-year-old male with advanced buccal mucosa squamous cell carcinoma who developed acute severe cutaneous toxicity following low dose of intravenous MTX therapy. After receiving two weekly doses, the patient experienced grade 4 oral mucositis and multiple erythematous plaques. This case highlights the importance of early recognition and prompt management of MTX toxicity, even at low doses, particularly in patients with risk factors such as prior antibiotic use and low serum albumin levels.</div></div>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"15 ","pages":"Article 102108"},"PeriodicalIF":0.0,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144829718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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