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Occurrence and dietary risk assessment of chloramphenicol residues in honey products in Saudi Arabia. 沙特阿拉伯蜂蜜制品中氯霉素残留的发生及膳食风险评估。
Toxicology Reports Pub Date : 2025-06-08 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102066
Lulu Almutairi, Abdullah AlSayari, Somaiah Almubayedh, Sarah AlSubaie, Thamer AlMudhehi, Malak Almutairi, Amani S Alqahtani
{"title":"Occurrence and dietary risk assessment of chloramphenicol residues in honey products in Saudi Arabia.","authors":"Lulu Almutairi, Abdullah AlSayari, Somaiah Almubayedh, Sarah AlSubaie, Thamer AlMudhehi, Malak Almutairi, Amani S Alqahtani","doi":"10.1016/j.toxrep.2025.102066","DOIUrl":"10.1016/j.toxrep.2025.102066","url":null,"abstract":"<p><strong>Background: </strong>Chloramphenicol (CAP) is a broad-spectrum antibiotic with potentially fatal side effects, including suspected carcinogenicity and toxicity in sensitive individuals. Due to these risks, CAP has been banned in food-producing animals, including honey, by regulatory authorities worldwide. This study investigates the presence of CAP residues in honey products from the Saudi market and evaluates the associated dietary exposure risk.</p><p><strong>Methods: </strong>A total of 902 honey samples collected during 2018-2019 were retrieved from the Saudi Food and Drug Authority (SFDA) to investigate honey safety and chemical components. CAP was extracted using a validated liquid-liquid extraction method and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Dietary exposure was assessed using the margin of exposure (MOE) approach, with relevant data on honey consumption and body weight sourced from published studies.</p><p><strong>Results: </strong>CAP residues were detected in 54 (6 %) of the tested honey samples, with a mean concentration of 0.16 ± 0.032 µg/kg. The 95th percentile MOE for adults was 31,752 in the lower-bound scenario and 24,290 in the upper-bound scenario, exceeding the critical threshold of 10,000 established by the European Food Safety Authority, which indicates low public health concern and low priority for risk management.</p><p><strong>Conclusion: </strong>Our findings indicate a low health risk associated with honey consumption in Saudi Arabia, as MOE values exceeded the critical safety threshold. However, ongoing monitoring, stricter regulations, and enhanced awareness are recommended to ensure the safety and quality of honey products.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102066"},"PeriodicalIF":0.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209939/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144544974","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
The effects of methamphetamine intoxication on acute kidney injury in Iraqi male addicts. 甲基苯丙胺中毒对伊拉克男性成瘾者急性肾损伤的影响。
Toxicology Reports Pub Date : 2025-06-06 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102065
Sazan A Mirza, Nawar S Mohammed, Zahraa Q Ali, Aseel Sameer Mohamed
{"title":"The effects of methamphetamine intoxication on acute kidney injury in Iraqi male addicts.","authors":"Sazan A Mirza, Nawar S Mohammed, Zahraa Q Ali, Aseel Sameer Mohamed","doi":"10.1016/j.toxrep.2025.102065","DOIUrl":"10.1016/j.toxrep.2025.102065","url":null,"abstract":"<p><p>Methamphetamine (METH), a synthetic derivative of amphetamine, is prescribed for disorders such as narcolepsy but is sometimes illicitly produced from over-the-counter drugs like pseudoephedrine to produce \"crystal meth.\" Consumption of METH can have a severe impact on a number of organ systems, including renal failure, neurotoxicity, pulmonary toxicity, and cardiotoxicity. Increased doses of METH can elevate blood pressure and heart rate, hence enhancing the chance of serious repercussions. Acute renal failure associated with METH is linked to kidney issues such as renal tubular necrosis, caused by reduced blood flow, and acute interstitial nephritis, which damages kidney tubules and impairs waste filtration. Biomarkers such as elevated serum levels of urea, creatinine, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL) indicate acute kidney injury (AKI). METH-induced renal failure often correlates with hyperthermia, hemodynamic instability, rhabdomyolysis, and nephropathies like necrotizing angiitis, tubular necrosis, and interstitial nephritis. This study investigates the association between kidney toxicity and AKI in Iraqi males with METH addiction. The research, carried out at Ibn-Rushed Psychiatric Hospital in Baghdad between January and August 2023, involved 168 males aged 22-43 who had been addicted for over 60 months. Additionally, 154 healthy males with no history of drug use served as controls. Drug test screening cards were utilized to confirm the diagnosis. Kidney function tests (urea, creatinine), total protein, serum albumin, sodium ions, cystatin C, creatine kinase, and NGAL levels were assessed. Results revealed significant differences between addicts and controls, particularly elevated cystatin C, creatine kinase, and NGAL levels in addicts. A ROC curve analysis demonstrated heightened sensitivity of kidney function tests to METH-induced renal damage. Histopathological examination of a deceased male, aged 41-year-old, with a seven-year history of METH abuse revealed evidence of acute kidney injury, accompanied by significantly elevated levels of renal function biomarkers. The findings suggest that prolonged methamphetamine use may have contributed to severe renal impairment, manifesting in both structural damage to the kidneys and a marked disruption in renal function. This study highlights the severe impact of METH on kidney function and underscores the importance of preventive measures and effective treatment strategies for managing METH addiction and mitigating its harmful effects.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102065"},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476798","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
Ferroptotic- and non-ferroptotic mechanisms associated with doxorubicin-induced male reproductive dysfunction. 与阿霉素诱导男性生殖功能障碍相关的嗜铁性和非嗜铁性机制。
Toxicology Reports Pub Date : 2025-06-04 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102064
E O Ajani, T M Akhigbe, P A Oyedokun, C A Adegbola, D H Adeyemi, R E Akhigbe
{"title":"Ferroptotic- and non-ferroptotic mechanisms associated with doxorubicin-induced male reproductive dysfunction.","authors":"E O Ajani, T M Akhigbe, P A Oyedokun, C A Adegbola, D H Adeyemi, R E Akhigbe","doi":"10.1016/j.toxrep.2025.102064","DOIUrl":"10.1016/j.toxrep.2025.102064","url":null,"abstract":"<p><p>Despite the effectiveness of doxorubicin as a chemotherapeutic agent, it exerts toxicity on non-target organs, including the male reproductive organs. This review synthesizes current evidence on both ferroptotic and non-ferroptotic mechanisms underlying doxorubicin (DOX)-induced male reproductive dysfunction. DOX disrupts testicular function by inducing oxidative stress, lipid peroxidation, mitochondrial dysfunction, and apoptosis, particularly in Leydig, Sertoli, and spermatogenic cells. These effects result in reduced testosterone production, impaired spermatogenesis, and poor semen quality. Additionally, DOX alters the hypothalamic-pituitary-gonadal (HPG) axis and downregulates key enzymes involved in steroidogenesis, exacerbating hormonal imbalances and infertility risks. Emerging research highlights ferroptosis, iron-dependent cell death, as a major contributor to DOX-induced testicular damage, with evidence showing that antioxidant agents like melatonin and zinc oxide nanoparticles may offer protective effects. In addition, the results of this review reveal the necessity of investigating the potential of interventional strategies. This research highlights the need for integrative care approaches prioritizing cancer management and fertility preservation. This review aims to inform healthcare providers, patients, and policymakers about the significant consequences of doxorubicin therapy and open new therapeutic horizons for adjuvant therapies.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102064"},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12179665/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476796","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
Genotoxic activity of glyphosate and co-formulants in glyphosate-based herbicides assessed by the micronucleus test in human mononuclear white blood cells. 用人单核白细胞微核试验评估草甘膦除草剂中草甘膦及其共制剂的基因毒性活性。
Toxicology Reports Pub Date : 2025-06-03 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102063
Khadija Ramadhan Makame, Yazen Aljaber, Moustafa Sherif, Balázs Ádám, Károly Nagy
{"title":"Genotoxic activity of glyphosate and co-formulants in glyphosate-based herbicides assessed by the micronucleus test in human mononuclear white blood cells.","authors":"Khadija Ramadhan Makame, Yazen Aljaber, Moustafa Sherif, Balázs Ádám, Károly Nagy","doi":"10.1016/j.toxrep.2025.102063","DOIUrl":"10.1016/j.toxrep.2025.102063","url":null,"abstract":"<p><p>Glyphosate-based herbicides (GBHs) are widely used and contribute to soil, water, and air contamination. Despite differing assessments of its carcinogenic potential, glyphosate toxicity may be enhanced by the co-formulants (adjuvants) used to improve its effectiveness. In this study, we investigated the genotoxic effects of glyphosate, alkyl dimethyl betaine (adjuvant A), and polyethoxylated tallow amine (adjuvant B) on human peripheral white blood cells using a cytokinesis block micronucleus (CBMN) assay. The experiments tested Glyphosate (0.1, 1, 10, and 100 μM) and adjuvants (at concentrations matching their levels in respective GBHs) in whole blood samples. The samples were exposed for 4 and 20 h with and without S9 metabolic treatment. The results showed that glyphosate and adjuvant A caused a statistically significant increase in the frequency of binucleated cells with micronuclei (BNMN%) only at 100 μM after 4-hour exposure without S9 treatment. Adjuvant B, however, induced a statistically significant increase in BNMN% starting at 1 μM after 4-hour exposure without S9 treatment. No significant effects were observed after 4 h of exposure with S9 or 20 h of exposure, with or without S9. The proliferation index (PI) showed no significant changes. This study concluded that the co-formulants in GBHs can induce genotoxic effects at low concentrations and short exposure times. This indicated that some surfactants in GBHs may be more toxic than glyphosate.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102063"},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12192614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498087","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
Naringin ameliorates high-fat diet-induced hepatotoxicity and dyslipidemia in experimental rat model via modulation of anti-oxidant enzymes, AMPK and SERBP-1c signaling pathways. 柚皮苷通过调节抗氧化酶、AMPK和SERBP-1c信号通路,改善实验大鼠高脂饮食诱导的肝毒性和血脂异常。
Toxicology Reports Pub Date : 2025-05-30 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102062
Sweata Sarkar, Sanjib Ghosh, Maharaj Biswas
{"title":"Naringin ameliorates high-fat diet-induced hepatotoxicity and dyslipidemia in experimental rat model via modulation of anti-oxidant enzymes, AMPK and SERBP-1c signaling pathways.","authors":"Sweata Sarkar, Sanjib Ghosh, Maharaj Biswas","doi":"10.1016/j.toxrep.2025.102062","DOIUrl":"10.1016/j.toxrep.2025.102062","url":null,"abstract":"<p><p>High-fat diet causes elevation of steatosis, dyslipidemia and oxidative stress which eventually leads to hepatic injury in the form of non-alcoholic fatty liver disease (NAFLD). Naringin, a natural flavonoid, having tremendous potentiality including antioxidant, anti-inflammatory, hypolipidemic role. Based on this proposition, we investigated the role of naringin in hepatotoxicity and its possible underlying mechanism caused by high-fat diet for prolonged time. Fifteen Wistar rats were divided into three groups: Group A (CON) received normal diet; Group B (HFD) was administered with high-fat diet for 16 weeks; and Group C (THN) was treated with naringin (100 mg/kg B.W.) for last 6 weeks after induction of obesity. After autopsy, various parameters were studied like gravimetry, serum biochemistry, ROS activity, anti-oxidant enzymes, genes expression (AMPK and SREBP-1C), histochemistry, histopathology and ultrastructure of hepatic tissue. In HFD group, Masson's trichome stain intensity increased 6.8-folds, indicating the onset of liver fibrosis; ROS generation and lipid peroxidation (TBARS) were significantly (p < 0.01) increased, whereas SOD and CAT were decreased by 36.7 % and 49.7 %, respectively. Furthermore, these parameters were remained normal in THN group. Besides, HFD group displayed extreme elevation in hepatic SREBP-1C expression (147 %) and downregulation of AMPK gene (77 %) compared to control. The ultrastructural study revealed most important and new insight of this study where HFD induced extreme reticule stress in hepatic tissue which was significantly improved by the treatment of naringin. These findings demonstrate that the naringin may be used as a potential therapeutic agent to combat obesity related hyperlipidemia and NAFLD.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102062"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302897","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
Assembled human microbiome and metabolome in chronic kidney disease: Dysbiosis a double-edged sword interlinking Circ-YAP1, Circ-APOE & Circ-SLC8A1. 慢性肾脏疾病中组装的人类微生物组和代谢组:Circ-YAP1, Circ-APOE和Circ-SLC8A1相互连接的生态失调双刃剑。
Toxicology Reports Pub Date : 2025-05-29 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102058
Eman A Zaki, Sherif M Afifi, Naglaa M Ammar, Mai O Kadry
{"title":"Assembled human microbiome and metabolome in chronic kidney disease: Dysbiosis a double-edged sword interlinking Circ-YAP1, Circ-APOE & Circ-SLC8A1.","authors":"Eman A Zaki, Sherif M Afifi, Naglaa M Ammar, Mai O Kadry","doi":"10.1016/j.toxrep.2025.102058","DOIUrl":"10.1016/j.toxrep.2025.102058","url":null,"abstract":"<p><p>Dysbiosis is an alteration in microbiota diversity previously elucidated in patients with chronic kidney disease (CKD). Relationship between dysbiosis and CKD is bidirectional; Uremic milieu disturbs the human microbiota on the other hand, gut metabolites influence CKD development. As a result, we outline the possible contribution of microbiota in the pathophysiology, diagnosis and monitoring of CKD. A growing body of research indicates that changes in circular RNAs (circ-RNAs) were observed in CKD with pathogenic implications, including modifying intracellular signaling, exaggerating oxidative stress, cellular apoptosis and inflammation. Additionally, Circ-RNAs exhibit promising role in clinical settings for monitoring, diagnosis, prognostication, and treatment of CKD. Herein blood samples were collected from 60 Egyptian patients with CKD as well as 60 healthy volunteers who served as controls. Following clinical evaluations, OPLS-DA and PCA GC-MS analysis were performed to detect metabolite perturbations. The levels of toxic uremic metabolites, such as urea, hexanedioic acid, ribonic acid, dodecanoic acid, pyrimidine, 1H-indole, 1H-indole-3-acetic acid, butanoic acid, L-cystine, and benzaldehyde linked to renal fibrosis were found to be elevated. Conversely, Reno-protective metabolites, such as short-chain fatty acids; 1H-indole were found to be negatively correlated with indole propionic acid, acetic acid, 2-propenoic acid, tryptophan, tyrosine, and glucitol (AUC 0.65) derived from the gut flora. CKD patients clarified an alteration both gene and protein expression of circRNAs (Circ-YAP1, circ-APOE, and circ-SLC8A1)/mTOR. Moreover, these biomarkers had a significant correlation with clinical investigations such as Creatinine, Glomerular filtration rate (GFR) and albumin/Creatinine (A/C) ratio. These results shed some light on the metabolic biomarkers that are associated with CKD and novel insights into metabolomics/microbiota/Circ-YAP1/circ-APOE/circ-SLC8A1/mTOR interlinked with disease prognosis/diagnosis that could be translated into clinically relevance.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102058"},"PeriodicalIF":0.0,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302894","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
Human health risks of heavy metals contamination of a water-soil-vegetables farmland system in Toke Kutaye of West Shewa, Ethiopia. 埃塞俄比亚西谢瓦Toke Kutaye水-土壤-蔬菜农田系统重金属污染的人类健康风险。
Toxicology Reports Pub Date : 2025-05-28 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102061
Getacho Feyisa, Birhanu Mekassa, Lemessa B Merga
{"title":"Human health risks of heavy metals contamination of a water-soil-vegetables farmland system in Toke Kutaye of West Shewa, Ethiopia.","authors":"Getacho Feyisa, Birhanu Mekassa, Lemessa B Merga","doi":"10.1016/j.toxrep.2025.102061","DOIUrl":"10.1016/j.toxrep.2025.102061","url":null,"abstract":"<p><p>Contamination of foods with heavy metals poses significant threats to human health. In this study, human health risks of heavy metals contaminated vegetables (cabbage, onion and green pepper) from irrigation farmlands in Toke Kutaye, Ethiopia were evaluated. Wet acid digestion of vegetables, supporting soil and irrigation water samples were employed prior to FAAS determination of heavy metals (Fe, Zn, Cu, Mn, Co, Cr, Ni, Cd and Pb). The measured average values of the studied heavy metals ranged from < 0.01-2.52 ± 0.06 mg/L, 2.25 ± 0.19-131.31 ± 0.13 mg/kg, and < 0.01-18.21 ± 0.17 mg/kg for water, soil and vegetable samples, respectively. The average concentration of the studied heavy metals in the vegetable samples were arranged in the order of Zn>Cu>Fe>Mn>Co>Ni>Pb>Cr>Cd. The heavy metals accumulation in the vegetables followed the order of cabbage > onion > green pepper. The mean values of Pb in the vegetables exceeded the WHO/FAO guideline value. The possible sources of the heavy metals were agrochemicals, domestic sewage wastes, manures and geogenic processes. The hazard quotient (HQ) and hazard index (HI) based human health risk assessment results indicated that the individual metals and their mixture could pose insignificant non-carcinogenic risk (HQ and HI < 1) to consumers. However, cancer risk assessment values for the individual Ni metal, and the mixture of Ni, Cr and Pb exceeded the threshold limit for both children and adults. These results highlight possible chronic carcinogenic risks due to exposure to heavy metals via consumption of contaminated vegetables from the study area, which requires the concern of the consumers and regulatory bodies.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102061"},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302896","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
The rs140668532 SNP in GSK-3β gene as a potential biomarker for Alzheimer's disease: Insights from computational modeling. GSK-3β基因rs140668532 SNP作为阿尔茨海默病的潜在生物标志物:来自计算模型的见解
Toxicology Reports Pub Date : 2025-05-28 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102060
İrem Gülfem Albayrak, Belkıs Atasever Arslan
{"title":"The rs140668532 SNP in GSK-3β gene as a potential biomarker for Alzheimer's disease: Insights from computational modeling.","authors":"İrem Gülfem Albayrak, Belkıs Atasever Arslan","doi":"10.1016/j.toxrep.2025.102060","DOIUrl":"10.1016/j.toxrep.2025.102060","url":null,"abstract":"<p><p>Glycogen synthase kinase-3 beta (GSK-3β) is well recognized for its role in diverse physiological processes, including apoptosis, mitochondrial function, and gene transcription regulation. The precise regulation of GSK-3β activity is critical for maintaining neuronal health, and dysregulation may result in disturbances in neurological functions. Polymorphisms in the GSK-3β gene may increase susceptibility to neurodegenerative disorders. To assess the structural and functional consequences of deleterious SNPs in GSK-3β, various in silico approaches was utilized. Analysis identified 27 deleterious SNPs in the GSK-3β gene, among which 10 were classified as damaging by SIFT, PolyPhen-2, and MutPred2. The Project Hope software simulated ten harmful mutations in the GSK-3β gene. The pathways associated with neurodegeneration involving the GSK-3β gene and its interacting genes were identified through the KEGG and GeneMANIA databases, respectively. The V317F mutation was shown to reduce GSK-3β inhibition by highly selective inhibitory ligand PF04802367 (PF-367) and impair the GSK-3β-Tau interaction. The influence of GSK3β on Aβ formation suggests that the V317F mutation has a tau-independent neurodegenerative impact. The experimental investigation of the V317F mutant GSK-3β's effect on neurodegeneration may enhance the understanding of the biomarker potential of rs140668532 in Alzheimer's disease.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102060"},"PeriodicalIF":0.0,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302898","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
Drugs or dissection? Unraveling a diagnostic puzzle in the ED: A case report on Tizanidine-Nifedipine interaction. 药物还是解剖?在急诊科解开一个诊断难题:蒂扎尼与硝苯地平相互作用的病例报告。
Toxicology Reports Pub Date : 2025-05-27 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102055
Muhammad Abd Ur Rehman, Maaz Uddin Mohammed, Muhammad Abdul Mannan, Waleed Salem
{"title":"Drugs or dissection? Unraveling a diagnostic puzzle in the ED: A case report on Tizanidine-Nifedipine interaction.","authors":"Muhammad Abd Ur Rehman, Maaz Uddin Mohammed, Muhammad Abdul Mannan, Waleed Salem","doi":"10.1016/j.toxrep.2025.102055","DOIUrl":"10.1016/j.toxrep.2025.102055","url":null,"abstract":"<p><p>Lower back pain is among the top ten reasons patients visit the emergency department (ED). Tizanidine, a centrally acting alpha-2 adrenergic receptor agonist, is commonly prescribed for managing spasticity in patients with cerebral or spinal injuries. It is also used as an effective treatment for nonspecific lower back pain. One of the most critical and life-threatening causes of lower back pain is abdominal aortic dissection, particularly in patients with hypertension. Nifedipine, a 1,4-dihydropyridine calcium channel blocker (CCB), is a widely used oral antihypertensive and antianginal agent. It lowers systemic vascular resistance and dilates coronary arteries by inhibiting calcium ion (Ca²⁺) entry into the smooth muscle cells of small arteries (arterioles), thereby reducing systemic blood pressure and improving myocardial oxygen delivery. We report a compelling case of a male patient presenting to the ED with high blood pressure and lower back pain. Shortly after the administration of tizanidine and nifedipine, his blood pressure dropped significantly within an hour. Initially suspected to be a ruptured abdominal aortic dissection, the cause was later identified as a drug-drug interaction. The synergistic effects of tizanidine and nifedipine resulted in a rapid and critical drop in blood pressure. The Drug Interaction Probability Scale (DIPS) score of 4 suggests the hypotensive episode was possibly caused by a drug interaction. This case also highlights the importance of point of care ultrasound (POCUS) and repeated examinations in excluding life-threatening conditions like aortic rupture.</p>","PeriodicalId":23129,"journal":{"name":"Toxicology Reports","volume":"14 ","pages":"102055"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12163400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302895","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
Analysis of pesticide residues in tomatoes from the tomato field and markets of KPK, Pakistan and their potential risk to human health. 巴基斯坦KPK番茄田和市场番茄中农药残留分析及其对人体健康的潜在风险。
Toxicology Reports Pub Date : 2025-05-26 eCollection Date: 2025-06-01 DOI: 10.1016/j.toxrep.2025.102059
Syeda Nazish-Ali, Nazia Rafique, Touqeer Taj, Saif Ullah, Farrakh Mehboob
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