Food and Chemical Toxicology最新文献_第6页

Deoxynivalenol induces spleen damage, apoptosis, and inflammation in mice by increasing mitochondrial reactive oxygen species: Protective effects of curcumin.

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-12 DOI: 10.1016/j.fct.2024.115200

Yuming Kuang, Zuoyao Wu, Yuqin Liu

{"title":"Deoxynivalenol induces spleen damage, apoptosis, and inflammation in mice by increasing mitochondrial reactive oxygen species: Protective effects of curcumin.","authors":"Yuming Kuang, Zuoyao Wu, Yuqin Liu","doi":"10.1016/j.fct.2024.115200","DOIUrl":"10.1016/j.fct.2024.115200","url":null,"abstract":"Deoxynivalenol (DON), a Fusarium mycotoxin, causes spleen apoptosis and inflammation, which damage the organ. Curcumin (Cur) is a member of the ginger family. It has anti-apoptotic and anti-inflammatory effects that maintain the health of the organism's immune system. Here, the protective effects of Cur against DON-induced spleen damage were explored. First, we found DON (2.4 mg/kg body weight) decreased the expression of manganese superoxide dismutase, mitochondrial membrane potential, adenosine triphosphate, and disturbed hematoxylin and eosin staining in mice spleen. The results confirmed that DON causes mitochondrial reactive oxygen species (mtROS) overproduction leading to spleen damage. Second, we found DON decreased the expression of mitochondrial apoptosis-inducing factor (AIF) and B-cell lymphoma-2 (Bcl-2), and increased the expression of nuclear AIF, Bcl2-associated X (Bax), cysteine-aspartate protease-3 (caspase-3), caspase-9. Mitoquinone is a mitochondria-targeted antioxidant that can prevent of mitochondrial oxidative damage. These expression increases were not observed in the mitoquinone-treated group, confirming that mtROS was an upstream regulatory target of apoptosis and inflammation in DON-exposed mice spleens. Finally, we confirmed that Cur (50 or 100 mg/kg body weight) attenuated DON-induced apoptosis and inflammation by inactivating mtROS. Collectively, these results confirm that DON causes spleen damage by increasing mtROS, and the protective effects of curcumin.","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115200"},"PeriodicalIF":3.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

RIFM fragrance ingredient safety assessment, 4-(4-methoxyphenyl)-3-methylbutan-2-one, CAS Registry Number 67828-19-7.

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-12 DOI: 10.1016/j.fct.2024.115197

A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar, Y Tokura

引用次数: 0

Triptolide exposure triggers ovarian inflammation by activating cGAS-STING pathway and decrease oocyte quality in mouse.

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-12 DOI: 10.1016/j.fct.2024.115201

Si-Yao Cheng, Yi-Fan Yang, Ya-Long Wang, Zhao-Ping Yue, Yan-Zhu Chen, Wen-Ke Wang, Zhi-Ran Xu, Lin-Feng Li, Hao Shen, Zhi-Min Qi, Chang-Long Xu, Yu Liu

{"title":"Triptolide exposure triggers ovarian inflammation by activating cGAS-STING pathway and decrease oocyte quality in mouse.","authors":"Si-Yao Cheng, Yi-Fan Yang, Ya-Long Wang, Zhao-Ping Yue, Yan-Zhu Chen, Wen-Ke Wang, Zhi-Ran Xu, Lin-Feng Li, Hao Shen, Zhi-Min Qi, Chang-Long Xu, Yu Liu","doi":"10.1016/j.fct.2024.115201","DOIUrl":"10.1016/j.fct.2024.115201","url":null,"abstract":"Triptolide (TPL), a prominent bioactive constituent derived from the Chinese herb Tripterygium wilfordii, exhibits diverse pharmacological effects such as anti-tumor and anti-immune properties. Despite its extensive clinical application for the treatment of arthritis and immune disorders, TPL has been associated with multiorgan toxicity, including adverse effects on the female reproductive system. However, the precise mechanisms underlying TPL-induced ovarian damage remain poorly understood. In this study, employing a mouse toxicological model, exposure to TPL was observed to result in decreased ovarian coefficient and fertility. Subsequent research demonstrated TPL exposure affected mitochondrial function, increased mitochondrial outer membrane permeability, resulted in mtDNA releasing into the cytoplasm. These events subsequently activated cGAS-STING pathway, leading to ovarian inflammation. Furthermore, TPL exposure has been found to disrupt the meiotic maturation of oocytes, which is mechanistically associated with suboptimal morphology of spindle and microtubule organizing centers (MTOCs). This association has been further confirmed through the use of reduced representation bisulfite sequencing (RRBS). In conclusion, our study demonstrates that TPL exposure can hinder follicular development, resulting in ovarian inflammation and reduced oocyte quality.","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115201"},"PeriodicalIF":3.9,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

RIFM fragrance ingredient safety assessment, trans-2-hexenyl acetate, CAS Registry Number 2497-18-9. RIFM 香料成分安全评估，反式-2-己烯乙酸酯，化学文摘社登记号 2497-18-9。

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-10 DOI: 10.1016/j.fct.2024.115188

A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar

引用次数: 0

Role of CYP2D6 polymorphisms in tramadol metabolism in a context of co-medications and overweight. CYP2D6 多态性在曲马多代谢中的作用与联合用药和超重有关。

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-10 DOI: 10.1016/j.fct.2024.115192

Pierre-Jean Ferron, Romain Pelletier, Julie Massart, Celine Narjoz, Vinh-Hoang-Lan Julie Tran, Marie-Anne Loriot, Angéline Kernalleguen, Marie Zins, Sofiane Kab, Isabelle Morel, Bruno Clément, Thomas Gicquel, Brendan Le Daré

{"title":"Role of CYP2D6 polymorphisms in tramadol metabolism in a context of co-medications and overweight.","authors":"Pierre-Jean Ferron, Romain Pelletier, Julie Massart, Celine Narjoz, Vinh-Hoang-Lan Julie Tran, Marie-Anne Loriot, Angéline Kernalleguen, Marie Zins, Sofiane Kab, Isabelle Morel, Bruno Clément, Thomas Gicquel, Brendan Le Daré","doi":"10.1016/j.fct.2024.115192","DOIUrl":"10.1016/j.fct.2024.115192","url":null,"abstract":"Very few quantitative data exist on tramadol metabolites, which hampers our understanding of their role in efficacy and safety of tramadol. We aimed to provide quantitative data on tramadol and its 5 main metabolites in a patient cohort and to determine whether metabolite ratios can be predictive of a CYP2D6 metabolism phenotype. We also aimed to investigate the influence of co-medications and patient profile (BMI, glycemia, lipid levels) on tramadol metabolite ratios. Overall, 37 patient samples from the CONSTANCES cohort contained tramadol and its 5 metabolites. Mean concentrations found tramadol at 343.2 ± 223.2 μg/L, M1 at 62.4 ± 41.4 μg/L, M2 at 210.0 ± 272.3, M3 at 1.76 ± 3.0 μg/L, M4 at 1.8 ± 2.8 μg/L and M5 at 31.8 ± 28.4 μg/L. The most frequent CYP2D6 phenotype was extensive metabolizers (51.3%), followed by intermediate metabolizers (24.3%) and poor metabolizers (10.8%). CYP2D6-inhibiting co-medications impacted tramadol metabolism independently of CYP2D6 metabolism phenotype. Lipid parameters and glycemia were significantly associated with changes in tramadol metabolic ratios. Metabolic ratios are not sufficient to determine the CYP2D6 metabolic phenotype in patients. CYP2D6 inhibitors and obesity/NAFLD/diabetes impact tramadol metabolism. These factors are likely to impact the analgesic efficacy and safety profile of tramadol, justifying the need for further studies in this area.","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115192"},"PeriodicalIF":3.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Editorial from the departing Editor-in-Chief.

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-10 DOI: 10.1016/j.fct.2024.115199

Bryan Delaney

引用次数: 0

Preclinical toxicity evaluation of the novel anti-hypertensive compound KSD179019. 新型抗高血压化合物 KSD179019 的临床前毒性评估

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-10 DOI: 10.1016/j.fct.2024.115195

Shaik Abdullah Nawabjan, Kailash Singh, Muthu Iswarya G S, Rex K H Au-Yeung, Fengwei Zhang, Li Zhang, Hani El-Nezami, Billy K C Chow

{"title":"Preclinical toxicity evaluation of the novel anti-hypertensive compound KSD179019.","authors":"Shaik Abdullah Nawabjan, Kailash Singh, Muthu Iswarya G S, Rex K H Au-Yeung, Fengwei Zhang, Li Zhang, Hani El-Nezami, Billy K C Chow","doi":"10.1016/j.fct.2024.115195","DOIUrl":"10.1016/j.fct.2024.115195","url":null,"abstract":"The Secretin receptor (SCTR) presents a promising path for hypertension management, with KSD179019 as identified as a Positive Allosteric Modulator (PAM) of SCTR, demonstrating anti-hypertensive effects in animal models. Our objective was to comprehensively evaluate the potential toxicity of KSD179019 through in vitro and in vivo investigations. Initial in vitro studies showed minimal toxicity in liver and kidney cells and non-mutagenicity in bacterial assays. A 14-day acute toxicity test indicated an LD50 over 5000 mg/kg body weight, suggesting a safe profile, yet necessitating further in vivo analysis before progressing to human trials. Following OECD protocols, we conducted sub-chronic (90 days) and chronic (180 days) toxicity studies in male and female C57 mice at various dosages. These included comprehensive hematological, biochemical, macroscopic, urinalysis, and histopathological examinations. The sub-chronic study reported minimal toxicity except at the highest doses (700 and 1000 mg/kg), while the chronic study suggested a no-observed-adverse-effect-level (NOAEL) at 250 mg/kg with limitations. QSAR analysis supported the non-mutagenic nature of KSD179019. KSD179019 demonstrated a favorable general toxicity profile at a dose of 250 mg/kg in a 180-day chronic testing study. However, further preclinical investigations, including assessments of in vivo mutagenicity, reproductive and developmental toxicity, and carcinogenicity, are required to comprehensively establish its safety profile.","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115195"},"PeriodicalIF":3.9,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

RIFM fragrance ingredient safety assessment, isolongifolene oxide, CAS Registry Number 26619-69-2.

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-10 DOI: 10.1016/j.fct.2024.115181

A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar, Y Tokura

引用次数: 0

Single and combined effect of chrysin and N-acetylcysteine against deltamethrin exposure in rats.

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-09 DOI: 10.1016/j.fct.2024.115191

Ahmet Eker, Gökhan Eraslan

{"title":"Single and combined effect of chrysin and N-acetylcysteine against deltamethrin exposure in rats.","authors":"Ahmet Eker, Gökhan Eraslan","doi":"10.1016/j.fct.2024.115191","DOIUrl":"10.1016/j.fct.2024.115191","url":null,"abstract":"Effects of chrysin and N-acetylcysteine on deltamethrin exposure in rats were investigated. Eighty male Wistar Albino rats, weighing between 150 and 200 g and aged 2-3 months, were used and evenly allocated into eight groups. The control group of rats received a corn oil vehicle. Chrysin (50 mg/kg.bw), N-acetylcysteine (50 mg/kg.bw), a combination of chrysin and N-acetylcysteine, deltamethrin (10 mg/kg.bw), deltamethrin combined with chrysin, deltamethrin combined with N-acetylcysteine, and a combination of deltamethrin, chrysin, and N-acetylcysteine were administered via oral gavage for a duration of 21 days. Tissue (liver, kidney, brain, testis, heart, lung) and blood of oxidative stress markers (MDA, NO, GSH, SOD, CAT, GSH-Px, GR, GST, G6PD), hepatic caspase 3, 9 and p53 protein levels, biochemical parameters (glucose, triglyceride, cholesterol, BUN, creatinine, uric acid, total protein, albumin, LDH, AST, ALT, ALP, PChE activities/levels), as well as rat body/organ weights and plasma/liver deltamethrin concentrations. The administration of chrysin and N-acetylcysteine independently did not alter the assessed parameters. Significant differences were observed in most parameters assessed in the deltamethrin-alone group compared to the control group, whereas the parameter values in the groups treated with chrysin, NAC, or their combination with deltamethrin were similar to those of the control.","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":" ","pages":"115191"},"PeriodicalIF":3.9,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142811529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Update to RIFM fragrance ingredient safety assessment, butyl alcohol, CAS registry number 71-36-3.

IF 3.9 3区医学

Food and Chemical Toxicology Pub Date : 2024-12-09 DOI: 10.1016/j.fct.2024.115185

A M Api, A Bartlett, D Belsito, D Botelho, M Bruze, A Bryant-Friedrich, G A Burton, M A Cancellieri, H Chon, M Cronin, S Crotty, M L Dagli, W Dekant, C Deodhar, K Farrell, A D Fryer, L Jones, K Joshi, A Lapczynski, D L Laskin, M Lavelle, I Lee, H Moustakas, J Muldoon, T M Penning, A H Piersma, G Ritacco, N Sadekar, I Schember, T W Schultz, F Siddiqi, I G Sipes, G Sullivan, Y Thakkar

引用次数: 0