Drug and Chemical Toxicology最新文献

The protective effects of neferine against paracetamol-induced liver injury are associated with the activation of SIRT1/Nrf2/HO-1 signaling pathway and inhibition of NF-kappa B/TNF-alpha/iNOS/COX-II cascade. 荷叶碱对扑热息痛肝损伤的保护作用与激活SIRT1/Nrf2/HO-1信号通路和抑制NF-kappa B/ tnf - α /iNOS/COX-II级联有关。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-20 DOI: 10.1080/01480545.2025.2559844

Mohammed A Altowijri, Marwa E Abdelmageed, Randa El-Gamal, Dina S El-Agamy

{"title":"The protective effects of neferine against paracetamol-induced liver injury are associated with the activation of SIRT1/Nrf2/HO-1 signaling pathway and inhibition of NF-kappa B/TNF-alpha/iNOS/COX-II cascade.","authors":"Mohammed A Altowijri, Marwa E Abdelmageed, Randa El-Gamal, Dina S El-Agamy","doi":"10.1080/01480545.2025.2559844","DOIUrl":"https://doi.org/10.1080/01480545.2025.2559844","url":null,"abstract":"Drug-induced hepatotoxicity is a significant public health issue that influences the development of novel pharmaceutical therapies and the retraction of numerous promising medications from the market.Therefore, the current study investigated the potential hepato-protective benefits of NEF against hepatotoxicity caused by paracetamol (APAP) in mice and assessed its underlying mechanisms. Mice were divided randomly into six groups; control (received normal saline), NEF control, APAP, N-acetylcysteine (NAC; served as a standard treatment) + APAP, NEF (10 mg/kg) + APAP, and NEF (20 mg/kg) + APAP. The serum and hepatic tissues were collected for different biochemical, genetic, and histological assessments. APAP induced profound hepatic damage that was evident through all biochemical, histological, and molecular assessments. NEF pretreatment opposed the elevation of liver injury biomarkers and attenuated hepatic histological disruption. At the molecular level, NEF increased the hepatic level and protein expression of SIRT-1. NEF increased the hepatic mRNA and protein expression of Nrf2 and HO-1. NEF also decreased hepatic level of oxidative stress biomarker, MDA and increased the hepatic levels of antioxidants: GSH, GR, GST, TAC, and SOD, NEF also counteracted the activation of NF-κB and inhibited the upregulation of different inflammatory cytokines as TNF-α and interleukins- (IL-1β and IL-6). Furthermore, NEF pretreatment decreased the hepatic level and mRNA expression of COX-II and iNOS. NEF ameliorated APAP-induced liver injury in mice where the higher dose of NEF (20 mg/kg) was more effective than the lower (10 mg/kg) compared to NAC. This effect is association with upregulation of SIRT-1/Nrf2/HO-1 and interruption of NF-κB/cytokines/iNOS/COX-II signaling cascades.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-16"},"PeriodicalIF":1.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145328515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute and subacute dermal toxicity analysis of film forming topical spray of meloxicam: in vitro and in vivo studies. 美洛昔康局部成膜喷雾剂的急性和亚急性皮肤毒性分析：体外和体内研究。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-17 DOI: 10.1080/01480545.2025.2527173

Harithasree Veerabomma, Vaskuri G S Sainaga Jyothi, Divya Atram, Rahul Kumar, Soham Loharkar, Sabiya Samim Khan, Dharmendra Kumar Khatri, Ankush Bansode, Santhosh Kumar Guru, Jitender Madan

{"title":"Acute and subacute dermal toxicity analysis of film forming topical spray of meloxicam: in vitro and in vivo studies.","authors":"Harithasree Veerabomma, Vaskuri G S Sainaga Jyothi, Divya Atram, Rahul Kumar, Soham Loharkar, Sabiya Samim Khan, Dharmendra Kumar Khatri, Ankush Bansode, Santhosh Kumar Guru, Jitender Madan","doi":"10.1080/01480545.2025.2527173","DOIUrl":"https://doi.org/10.1080/01480545.2025.2527173","url":null,"abstract":"Meloxicam is used in the treatment of clinical mastitis to promote milk production. Therefore, in the present investigation, acute and sub-acute dermal toxicity of our prototype film-forming topical dermal spray of meloxicam was carried out in addition to the dermal permeation rate. Implementing the OECD test norms, acute and repeated dose analyses were carried out in male and female groups of rats. Film-forming topical dermal spray of meloxicam released 68.62% of the drug over a 24-h period with a permeation rate of 22.58-µg/cm2. The lethal dose 50 (LD50) for film-forming topical dermal spray of meloxicam may be considered to be >2000 mg.kg-1. Various hematological, biochemical and histopathological parameters were examined post-treatment in sub-acute toxicity. Film-forming dermal spray of meloxicam at low and moderate doses did not exhibit any adverse effects on the skin and mammary glands whereas the high dose had shown hyperplasia in the tubuloalveolar area of mammary glands. Hence, the\"no observed adverse effect level (NOAEL) was considered to be 1000-mg.kg-1 in experimental animals. The IC50 value for blank film-forming topical dermal spray and meloxicam film-forming topical dermal spray was found to be 2.655-µg/mL, and 1.871-µg/mL, respectively, as compared to 229.18-µg/mL of meloxicam solution at 72 h against normal breast epithelial, MCF-10A cells. Hence, meloxicam film forming dermal spray retains the normal breast epithelial cell viability at low to moderate doses in both in vitro and in vivo applications. In conclusion, the moderate dose of film-forming dermal spray of meloxicam was found to be safe for topical use.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":1.9,"publicationDate":"2025-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145307195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardioprotective effect of apigenin and carvedilol against isoproterenol-induced myocardial infarction in rats. 芹菜素和卡维地洛对异丙肾上腺素所致大鼠心肌梗死的保护作用。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-16 DOI: 10.1080/01480545.2025.2565350

Rehnuma Siddiquee, Tarique Mahmood, Vaseem Ahamad Ansari, Farogh Ahsan, Shahzadi Bano, Sana Ahmad, Mohd Masih Uzzaman Khan

{"title":"Cardioprotective effect of apigenin and carvedilol against isoproterenol-induced myocardial infarction in rats.","authors":"Rehnuma Siddiquee, Tarique Mahmood, Vaseem Ahamad Ansari, Farogh Ahsan, Shahzadi Bano, Sana Ahmad, Mohd Masih Uzzaman Khan","doi":"10.1080/01480545.2025.2565350","DOIUrl":"https://doi.org/10.1080/01480545.2025.2565350","url":null,"abstract":"Myocardial infarction remains one of the leading causes of mortality and morbidity globally. While apigenin (AP), a trihydroxyflavone, and carvedilol, a beta blocker, have both been utilized in the treatment of cardiovascular diseases. There is a notable lack of comprehensive research or limited data regarding their combined cardioprotective activity. This gap emphasizes the need for further investigation into the potential synergistic effects of AP and carvedilol in the context of myocardial infarction. This study aims to evaluate the cardioprotective effect of AP and carvedilol in isoproterenol-induced myocardial infarction in rats. Male Sprague-Dawley rats were used and divided into five groups (n = 6). Isoproterenol (85 mg/kg/s.c.) was administered to induce myocardial infarction. AP (50 mg/kg/day/p.o) and carvedilol (5 mg/kg/day/p.o) were administered to rats for 14 days, along with Isoproterenol on the 15th and 16th days. Various parameters were estimated, including biochemical markers, cardiac markers, oxidative stress markers, antioxidants, and lipid profiles, to observe the effects of flavonoids and drugs. Administration of Isoproterenol showed changes in physical parameters, significantly elevated levels of serum biochemical markers, cardiac markers, oxidative stress markers, lipid profile, and decreased antioxidant enzymes. Treatment with AP and carvedilol diminished these changes very significantly. Histopathological examination of heart tissue in isoproterenol-induced rats showed necrotic lesions, which were reduced by the treatment with test drugs alone and in combination. Our study demonstrated that AP alone and in combination with carvedilol showed cardioprotective activity over isoproterenol-induced myocardial infarction in rats. Further investigations are needed to explore the underlying mechanism.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-17"},"PeriodicalIF":1.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Acute and sub-acute toxicological evaluation of a bioactive compound mixture in healthy Wistar rats. 一种生物活性化合物混合物对健康Wistar大鼠急性和亚急性毒理学评价。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-16 DOI: 10.1080/01480545.2025.2565712

Thushara Indika Sampath, Susanthi Jayasinghe, Anoja Priyadarshani Attanayake, Veranja Karunaratne

{"title":"Acute and sub-acute toxicological evaluation of a bioactive compound mixture in healthy Wistar rats.","authors":"Thushara Indika Sampath, Susanthi Jayasinghe, Anoja Priyadarshani Attanayake, Veranja Karunaratne","doi":"10.1080/01480545.2025.2565712","DOIUrl":"https://doi.org/10.1080/01480545.2025.2565712","url":null,"abstract":"The increasing interest in bioactive compounds necessitates a thorough understanding of their in vivo safety profiles before they are developed as therapeutic drug leads. The present study aimed to evaluate acute and sub-acute toxicological effects of a compound mixture composed of garcinol, piperine, butyl oleate, pipnoohine, and bismurrayanimbine, combined in a molar mass ratio of 9:33:1:4:1 at the doses of 10 mg kg-1, 25 mg kg-1, and 50 mg kg-1 in healthy Wistar rats, following Organization for Economic Co-operation and Development guidelines. A single oral dose of the compound mixture (10 mg kg-1, 25 mg kg-1, and 50 mg kg-1) was administered, and the rats were closely observed over a subsequent 14-day period. Further, the compound mixture was administered orally at the same three doses to Wistar rats continuously for 28 days. The compound mixture at the three doses did not produce mortality or abnormal behavioral changes throughout the 14 days. No significant alterations in hematological parameters or biochemical markers such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and creatinine (p > 0.05) were observed. Histopathological analysis revealed no treatment-related changes in the hematoxylin and eosin-stained sections of the liver, kidney, heart, spleen, stomach, small intestine, and lung tissues. In conclusion, the oral administration of compound mixture at 10 mg kg-1, 25 mg kg-1, and 50 mg kg-1 for 28 days was found to be safe in healthy Wistar rats via biochemical (liver enzymes, kidney function tests), hematological (full blood count analysis), and histological assessments of hematoxylin and eosin-stained tissue sections.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-12"},"PeriodicalIF":1.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synergistic hepatoprotection by supplementing Saussurea costus (falc.) lipsch and Glycyrrhiza glabra L. in combination against Diethylnitrosamine-induced liver damage in rats. 雪莲、甘草联合对二乙基亚硝胺所致大鼠肝损伤的协同保护作用。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-16 DOI: 10.1080/01480545.2025.2564431

Bisen Harsh, Rakesh Kumar, R K Asrani, Joshi Gaurav Santoshrao, Ekta Bisht, Shreya Katoch, Vinesh Sharma, Vikarm Patial, Adarsh Kumar

{"title":"Synergistic hepatoprotection by supplementing Saussurea costus (falc.) lipsch and Glycyrrhiza glabra L. in combination against Diethylnitrosamine-induced liver damage in rats.","authors":"Bisen Harsh, Rakesh Kumar, R K Asrani, Joshi Gaurav Santoshrao, Ekta Bisht, Shreya Katoch, Vinesh Sharma, Vikarm Patial, Adarsh Kumar","doi":"10.1080/01480545.2025.2564431","DOIUrl":"https://doi.org/10.1080/01480545.2025.2564431","url":null,"abstract":"This study aims to evaluate the hepatoprotective effects of combined Saussurea costus and Glycyrrhiza glabra extracts against diethylnitrosamine (DEN)-induced hepatic damage in rats. In the present investigation, the in vivo experimental study involved forty-two male Albino Wistar rats allocated into seven groups of six rats in each. Group I served as the vehicle control (10% DMSO) and Group II was administered DEN at a concentration of 0.01% in drinking water. Group III received both DEN and silymarin at 25 mg/kg bw. Groups IV and V were treated with individual extracts of S. costus and G. glabra at 250 mg/kg bw, respectively. Groups VI and VII received combined lower (LDC) and higher doses (HDC) of both plant extracts i.e., 125 mg/kg bw and 250 mg/kg bw, respectively. The ultrasonographic evaluation revealed a significant increase in hepatic echotexture in the positive control group compared to ameliorative groups provided with various plant extract combinations depicting minimal changes comparable to the standard control i.e., rats provided with silymarin. Serum levels of ALT, AST, ALB, creatinine, and LPO indicating liver damage were diminished in the various treatment groups compared to group II receiving DEN only.Therefore, the current study concluded that the higher combined dosage of the root extracts of S. costus and G. glabra i.e., 250 mg/kg bw each, demonstrated the hepatoprotective effect against DEN-induced liver damage in the rat model.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-13"},"PeriodicalIF":1.9,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparative histological, immunohistochemical, and biochemical effects of three orally administered fluoroquinolones in rats. 三种口服氟喹诺酮类药物对大鼠的组织学、免疫组织化学和生化作用的比较。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-14 DOI: 10.1080/01480545.2025.2565710

Turan Yaman, Fatih Donmez, Abdulahad Dogan, Abdulhamit Battal

{"title":"Comparative histological, immunohistochemical, and biochemical effects of three orally administered fluoroquinolones in rats.","authors":"Turan Yaman, Fatih Donmez, Abdulahad Dogan, Abdulhamit Battal","doi":"10.1080/01480545.2025.2565710","DOIUrl":"https://doi.org/10.1080/01480545.2025.2565710","url":null,"abstract":"Fluoroquinolones (FQs) are potent, broad-spectrum bactericidal antibiotics commonly used to treat infections in both humans and animals. Despite their therapeutic efficacy, their potential reproductive toxicity remains a concern. This study aimed to evaluate the histological, immunohistochemical, and biochemical effects of three FQ derivatives-ciprofloxacin (CIP), levofloxacin (LVX), and moxifloxacin (MXF)-on the testicular tissue of rats over different time intervals. Seventy-two male Wistar albino rats were randomly divided into four groups (n = 18): Control, CIP (80 mg/kg), LVX (40 mg/kg), and MXF (40 mg/kg). Treatments were administered orally, and testicular samples were collected at three time points (Day 1, 7, and 14). Histopathological evaluation was performed using hematoxylin and eosin staining. Cyclooxygenase-2 (COX-2) expression was assessed immunohistochemically. Biochemical analyses included measurements of malondyaldehyde (MDA), adenosine deaminase (ADA), and acetylcholine esterase (AChE) levels. FQ exposure led to variable degrees of testicular degeneration and significantly increased COX-2 expression in the testis. MXF administration caused a time-dependent reduction in MDA levels. ADA activity was significantly elevated in the CIP group on Day 1 and in the LVX group on Day 14. AChE levels were notably increased in both the LVX and MXF groups on Day 1 compared to controls. These findings suggest that FQ derivatives may exert time-dependent degenerative and inflammatory effects on testicular tissue, highlighting their potential risk for male reproductive toxicity.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-10"},"PeriodicalIF":1.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Physcion alleviates cisplatin-induced apo in HK-2 cells by activating the apo signaling for treating acute kidney injury: Integrating network pharmacology and informatics. physion通过激活载脂蛋白信号缓解顺铂诱导的HK-2细胞载脂蛋白，治疗急性肾损伤：整合网络药理学和信息学。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-14 DOI: 10.1080/01480545.2025.2559822

Wanyao Yan, Fang Zhou, Gailing Li, Yunjiao Wei, Li Tao, Li Liu

{"title":"Physcion alleviates cisplatin-induced apo in HK-2 cells by activating the apo signaling for treating acute kidney injury: Integrating network pharmacology and informatics.","authors":"Wanyao Yan, Fang Zhou, Gailing Li, Yunjiao Wei, Li Tao, Li Liu","doi":"10.1080/01480545.2025.2559822","DOIUrl":"https://doi.org/10.1080/01480545.2025.2559822","url":null,"abstract":"This research leverages the traditional Chinese medicine systems pharmacology (TCMSP) and Encyclopedia of traditional Chinese medicine (ETCM) to identify Chinese herbal remedies for (AKI) treatment. Lycii Fructus was found to be a potential candidate, and its pharmacological effects and molecular mechanisms were explored. Key targets of Lycii Fructus for AKI were identified and integrated into a \"Herb-Ingredient-Target-Disease\" (HITD) network. Through network pharmacology (NP) and literature review, physcion (PHY), a compound found in Lycii Fructus, was identified as a potential active ingredient targeting the Bcl2 gene, with apoptosis (Apo) proposed as the mechanism for its effects on AKI. To investigate this, a cisplatin-induced Apo model in human renal tubular epithelial cells (HK-2) was established. The study revealed that dose-dependent PHY administration substantially reduced cisplatin-induced Apo in HK-2 cells, as shown by CCK-8 assays and flow cytometry. We treated HK-2 with cisplatin at 5 mg L-1, treatment is carried out with different concentrations of PHY, to investigate the effect of PHY on the survival rates, the apoptosis rates and expressions of Bcl2/Bax protein of cells. CCK-8 assays showed, the survival rates of the cells in the groups with PHY therapeutic concentrations of 20 μmol L-1,40 μmol L-1 and 60 μmol L-1, the increase value compared with the cisplatin group were 8.40%, 31.67% and 37.19% respectively (P < 0.01) as well as apoptosis rates of the cells in the groups with PHY therapeutic concentrations of 40 μmol L-1 and 60 μmol L-1, the decrease in compared with the cisplatin group were 14.20% and 26.28% respectively (P < 0.01). Overall, PHY alleviated cisplatin-induced Apo in HK-2 cells by activating the Apo signaling.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-9"},"PeriodicalIF":1.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145285719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Potassium bromate-induced oxidative damage and nephrotoxicity in rats is ameliorated by vitamin C. 维生素C可改善溴酸钾引起的大鼠氧化损伤和肾毒性。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-14 DOI: 10.1080/01480545.2025.2573095

Saima Nazir, Mir Kaisar Ahmad, Zubair- Ul-Nazir

{"title":"Potassium bromate-induced oxidative damage and nephrotoxicity in rats is ameliorated by vitamin C.","authors":"Saima Nazir, Mir Kaisar Ahmad, Zubair- Ul-Nazir","doi":"10.1080/01480545.2025.2573095","DOIUrl":"https://doi.org/10.1080/01480545.2025.2573095","url":null,"abstract":"Potassium bromate (KBrO3), a widely used food-additive and a major water disinfection by-product, causes severe toxicity in humans and experimental animals. Bromate is considered a probable human carcinogen and a complete carcinogen in animals. We have investigated the potential role of vitamin C in mitigating KBrO3-induced nephrotoxcity. Animals were given KBrO3 alone or after pretreatment with vitamin C and then sacrificed. Blood and kidneys were collected and were used for the analysis of several biochemical parameters. Administration of single oral dose of KBrO3 alone caused nephrotoxicity as evident by elevated serum creatinine (+3-fold) and urea levels (+2.5-fold). Renal lipid peroxidation (+1.5-fold) and protein carbonyls (+2.5 fold) were increased while total sulfhydryl groups (-2.3-fold) and reduced glutathione levels (-1-fold) were decreased suggesting the induction of oxidative stress. The enzymes of renal brush border membrane were inhibited and those of carbohydrate metabolism were altered. There was increase in DNA damage and DNA-protein cross-linking. Treatment with vitamin C, prior to administration of KBrO3, resulted in significant attenuation in all these parameters but the administration of vitamin C alone had no effect. Histological studies supported these biochemical results showing extensive renal damage in KBrO3 alone treated animals and greatly reduced tissue injury in the vitamin C + KBrO3 group. These results show that vitamin C is an effective chemoprotectant against bromate-induced renal damage and could prove to be useful in attenuating the toxicity of this and other related compounds.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-11"},"PeriodicalIF":1.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Butylated hydroxytoluene protects against sodium arsenite-induced hepatorenal toxicities: in vivo and in silico studies. 丁基羟基甲苯防止亚砷酸钠引起的肝肾毒性：体内和硅研究。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-14 DOI: 10.1080/01480545.2025.2566438

A M Adegoke, S A Gazali, O O Latinwo, O A Akinbode, O M Ogunyemi, J K Akintunde

{"title":"Butylated hydroxytoluene protects against sodium arsenite-induced hepatorenal toxicities: in vivo and in silico studies.","authors":"A M Adegoke, S A Gazali, O O Latinwo, O A Akinbode, O M Ogunyemi, J K Akintunde","doi":"10.1080/01480545.2025.2566438","DOIUrl":"https://doi.org/10.1080/01480545.2025.2566438","url":null,"abstract":"Arsenic is a global environmental contaminant. Sodium arsenite (NaAsO2), one of the arsenic compounds, is toxic. Prolonged exposure to NaAsO2 causes various detrimental effects on body organs. Butylated hydroxytoluene (BHT), a synthetic antioxidant may retard the deleterious effects of free-radical-induced damage. We hereby investigated the chemo-protective role of BHT on sodium arsenite-induced hepatorenal toxicity in rats. Rats (n = 49, 110 ± 10 g) were grouped into seven with 7 animals each: groups 1 and 2 served as the negative controls and were administered corn oil and distilled water respectively, group 3 NaAsO2 (2.5 mg/kg); Group 4 BHT (25 mg/kg); Group 5 BHT (50 mg/kg); Group 6 BHT (25 mg/kg) + NaAsO2, and Group 7 BHT (50 mg/kg) + NaAsO2, for 14 days. Liver and kidney functions were assessed based on their specific markers, and inflammation, oxidative stress, and antioxidant profiles were evaluated spectrophotometrically. Molecular docking simulation was employed for in silico studies. Results revealed that NaAsO2 caused a notable increase in the serum activities of AST, ALT, ALP, urea and creatinine levels. Furthermore, there was a significantly increased oxidative stress and inflammatory markers with a concomitant decrease in antioxidant markers in the group exposed to NaAsO2 alone. Conversely, there were reversals of these effects in the groups co-exposed to NaAsO2 and BHT. Molecular docking revealed that BHT exhibited a high binding affinity for cyclooxygenase (COX) and interacted with critical amino acids in the active site of the enzymes.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-15"},"PeriodicalIF":1.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A new perspective on the neurotoxic mechanisms of six typical per- and polyfluoroalkyl substances (PFAS): insights from integrating network toxicology and random forest algorithm. 六种典型的全氟烷基和多氟烷基物质（PFAS）神经毒性机制的新视角：整合网络毒理学和随机森林算法的见解。

IF 1.9 4区医学

Drug and Chemical Toxicology Pub Date : 2025-10-14 DOI: 10.1080/01480545.2025.2572631

Wei Cheng, Peng Lin, Zhina Yang, Yulu Xie, Di Gao, Min Chen

{"title":"A new perspective on the neurotoxic mechanisms of six typical per- and polyfluoroalkyl substances (PFAS): insights from integrating network toxicology and random forest algorithm.","authors":"Wei Cheng, Peng Lin, Zhina Yang, Yulu Xie, Di Gao, Min Chen","doi":"10.1080/01480545.2025.2572631","DOIUrl":"https://doi.org/10.1080/01480545.2025.2572631","url":null,"abstract":"Per- and polyfluoroalkyl substances (PFAS) are widely used in various industries but pose significant ecological and human health risks, particularly to the nervous system. However, the underlying neurotoxic mechanisms remain poorly understood. This study combines network toxicology and machine learning to explore these mechanisms. Using ADMETLAB 3.0, we assessed the environmental toxicity of six common PFAS and identified their potential targets using online tools. A compound-target interaction network was built, followed by protein-protein interaction (PPI) and KEGG pathway analyses to investigate toxicological pathways. Core targets were selected through machine learning, and differential gene expression was analyzed using transcriptomic data. Molecular docking simulations predicted binding affinities between PFAS and their core targets, while molecular dynamics simulations on key complexes were performed using Gromacs 2023.2 and the Charmm36 force field. PFDS showed the highest bioconcentration factors (BCF), while PFOA demonstrated the greatest toxicity. We identified 62 intersecting targets, with PTGS2, MMP9, and ESR1 being central in the PPI network. Transcriptomic analysis revealed 1,077 differentially expressed genes (DEGs), highlighting associated biological processes and pathways. The random forest model identified 20 core genes, with 9 significantly differentially expressed in the PFAS-treated group. Molecular docking suggested potential interactions between the compounds and core targets, and molecular dynamics simulations further supported the stability of the complexes under physiological conditions. This study provides valuable insights into the neurotoxic mechanisms of PFAS, enhancing our understanding of their impact on the nervous system.","PeriodicalId":11333,"journal":{"name":"Drug and Chemical Toxicology","volume":" ","pages":"1-19"},"PeriodicalIF":1.9,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145291439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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