JOURNAL OF FOOD SCIENCE
·
2018
·Vol. 83
·期 2
·565-573
·
IF 2.018
Lingying Luo,Yun Bai,Guanghong Zhou
3-Amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) is a group 2B carcinogen characterized by the International Agency for Research on Cancer (IARC) and great efforts have been taken to reduce Trp-P-1 mutagenicity to humans. In this study, the effect of a reduction of Trp-P-1 on intestinal absorption as a promising strategy was investigated. The data showed that when 20 mM Trp-P-1 cotransported with 10 mM of sodium carboxymethyl cellulose (CMC), xanthan gum, or carrageenan, the absorption rate of Trp-P-1 was reduced by 31.5%, 49.5%, or 72.9% in MDCK-MDR1 cell monolayer, respectively; and 64.6%, 83.4%, or 64.1% in rat intestinal tissues, correspondingly. These 3 polysaccharides also reduced pharmacokinetic parameters, that is, C max , AUC 0-t , and AUC 0-∞ , after Trp-P-1 was given to rats intragastrically. However, gum arabic did not exhibit similar effects on Trp-P-1 absorption in vitro or in vivo . The Ames test showed that these 3 polysaccharides reduced Trp-P-1 mutagenicity to Salmonella typhimurium TA98, but gum arabic did not. Isothermal titration calorimetry assay indicated that Trp-P-1 interacted with these 3 polysaccharides. Thermodynamic study showed that the actual value of △ H <0, but its absolute value greater than the corresponding value of T∆S, suggest a specific interaction between Trp-P-1 and these 3 polysaccharides, probably through the hydrogen bond and/or ion interaction. Reduction of Trp-P-1 intestinal absorption using food additives could be one of the strategies to suppress Trp-P-1-induced carcinogenesis in human. Practical Application 1. This study provides insightful information for the food industry how gum arabic, xanthan gum, kappa carrageenan, and sodium carboxymethyl cellulose affect the absorption of Trp-P-1. 2. This study also provides novel information regarding a better formulation for meat products to reduce Trp-P-1 absorption.
研究领域:
营养学
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毒理学
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食品科学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Dong Zhen,Tang Shu-sheng,Ma Xiao-lan,Tan Bin,Tang Zhao-shan,Li Chang-hong,Yang Zi-hui,Zeng Jian-guo
The protopine alkaloids are widely distributed within the opium poppy family and have a wide range of pharmacological effects. MPTA is a product of the protopine total alkaloids extracted from the Macleaya cordata (Willd.) R. Br. Previously, we reported good anti-inflammatory activity of MPTA as well as oral acute and sub-chronic toxicity studies in rats. In order to perform a systematic toxicological safety assessment of MPTA, oral acute toxicity, genotoxicity (bone marrow cell chromosome aberration test, sperm abnormality test, bone marrow cell micronucleus test, and rat teratogenicity test), and chronic toxicity in mice were performed in this study. In the oral acute toxicity test, the LD50 in ICR mice was 481.99 mg/kg, with 95% confidence limits ranging from 404.27 to 574.70 mg/kg. All three mutagenicity tests tested negative in the range of 60.25–241.00 mg/kg. The results of the teratogenicity test in rats showed no reproductive or embryonic developmental toxicity at only 7.53 mg/kg, which can be considered as a no observed effect level (NOEL) for the teratogenicity test. Therefore, MPTA is safe for use at the doses tested, but attention should be paid to the potential risk to pregnant animals and the safety evaluation and toxicity mechanisms in target animals should be further investigated.
研究领域:
毒理学
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药理学
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遗传学
✓ 已验证
DOI
PubMed
高影响因子
Foods
·
2024
·Vol. 13
·期 9
·1404
·
IF 4.7
Yuyang Yao,Juer Liu,Qiming Miao,Xinyue Zhu,Wei Hua,Na Zhang,Guangwei Huang,Xiangyang Lin,Shengquan Mi,Yanling Cheng,Roger Ruan
Almond hull, a substantial byproduct comprising more than half of almond fresh weight, has recently gained attention due to its functionality and sustainability benefits. Despite heightened interest, information regarding its toxicity remains limited. In order to assess its genotoxic potential, we conducted Good Laboratory Practice-compliant in vitro and in vivo studies following Organization for Economic Co-operation and Development (OECD) guidelines. No evidence of toxicity or mutagenicity was observed in a bacterial reverse mutation assay using five tester strains, evaluating almond hull at concentrations up to 5 mg/plate, with or without metabolic activation. Almond hull did not induce chromosome structural damage in a chromosome aberration assay using Chinese hamster ovary cells, nor did it cause any spermatogonial chromosomal aberration in tested male BALB/c mice. To evaluate its ability to induce DNA damage in rodents, a combined micronucleus assay was conducted in KM mice of both sexes. Almond hull was administered at doses of 1250, 2500, and 5000 mg/kg/day via gavage once daily for 2 days. No adverse effects of almond hull were observed in the micronucleus assay. Our results indicate no evidence of the genotoxic potential of almond hull administered up to the maximum concentrations of 5 g/kg, as recommended by OECD guidelines.
研究领域:
食品科学
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毒理学
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遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
·
2023
·
IF 3.5
Jingjing Qu,Yinjing Zhang,Chunxia Liu,Qianqian Xie,Tong Ou,Bolin Fan,Yan Song
Anthraquinone is a recently identified contaminant present in teas globally, and its potential teratogenic and genotoxic impacts have yet to be fully comprehended. Hence, this study's objective was to determine anthraquinone's genotoxicity using various studies such as the Ames test , Mammalian erythrocyte micronucleus test, and in-vitro mammalian chromosome aberration study. Additionally, the study assessed its effects on maternal gestational toxicity and the fetus's teratogenicity through prenatal developmental toxicity research in rats. Results indicated that anthraquinone did not manifest mutagenic effects on Salmonella typhimurium histidine-deficient, did not cause chromosomal aberrations in Chinese hamster ovary cell subclone CHO-K1, and did not exhibit a genotoxic effect on mouse bone marrow erythrocytes. However, in the prenatal developmental toxicity study, administering anthraquinone orally to pregnant rats from day 5 to day 19 of gestation resulted in decreased body weight and food consumption of pregnant rats, along with a higher number of visceral malformations in the fetuses in the highest dose group (217.6 mg/kg BW). Additionally, two pregnant rats died in this group. The study has established the no observed adverse effect level (NOAEL) as 21.76 mg/kg BW, while the lowest observed adverse effect level (LOAEL) was 217.6 mg/kg BW.
研究领域:
毒理学
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遗传学
·
生殖医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2015
·Vol. 35
·期 11
·1415-1426
·
IF 2.982
Xu Wang,Ziqiang Tan,Yuanhu Pan,Awais Ihsan,Qianying Liu,Lingli Huang,Guyue Cheng,Dongmei Chen,Yanfei Tao,Zhenli Liu,Zonghui Yuan
Aditoprim (ADP), a new developed dihydrofolate reductase (DHFR) inhibitor, has great potential in clinical veterinary medicine because of its greater pharmacokinetic properties than structural analogs. Preclinical toxicology studies were performed to assess the safety of ADP including an acute oral toxicity test, a subchronic toxicity test and five mutagenicity tests. In the acute oral toxicity test, ADP was administered singly by oral gavage to Wistar rats and Kunming mice. The LD 50 calculated was 1400 mg kg –1 body weight (BW) day –1 in rats and 1130 mg kg –1 BW day –1 in mice. In a subchronic study, Wistar rats were administered ADP at dose levels of 0, 20, 100 and 1000 mg kg –1 diet for 90 days. Significant decreases were observed on body weight and food efficiency in the high-dose group. Treatment-related changes in clinical serum biochemistry were found in the medium- and high-dose groups. Significant increases in the relative weights of livers and kidneys in females and testis in males in the 1000 mg kg –1 diet, and significant decrease in relative weights of livers in males in the 100 mg kg –1 diet were noted. Histopathological observations revealed that the 1000 mg kg –1 ADP diet could induce lymphocytic infiltration and hepatocytic necrosis near the hepatic portal area. The genotoxicity of ADP was negative in tests, such as the bacterial reverse mutation assay, mice bone marrow erythrocyte micronucleus assay, in vitro chromosomal aberration test, in vitro cho/hgprt mammalian cell mutagenesis assay and mice testicle cells chromosome aberration. Based on the subchronic study, the no-observed-adverse-effect level for ADP was a 20 mg kg –1 diet, which is about 1.44-1.53 mg kg –1 BW day –1 in rats. Copyright © 2015 John Wiley & Sons, Ltd.
研究领域:
药理学
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毒理学
·
兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2021
·Vol. 16
·期 9
·e0255504
·
IF 3.24
Jing Zhang,Zhou-Tao Pei,Ya-Ni Zhao,Meng Zhang,Li-Ling Zhang,Wen-Qiang Wang,Jing-Ya Wu,Ran Yu,Li-Wei Sun
Benzophenone (BPs) and 4-Methylbenzylidene Camphor are used as ultraviolet (UV) filters to protect the skin and hair in personal care products. The discharging of the three chemicals may endanger the receiving water ecosystem. In the present study, the mutagenicity of BP-6, BP-8, and 4-Methylbenzylidene Camphor was tested using the Salmonella typhimurium reverse mutation test (Ames test) in the system with and without rat liver microsomal preparations (S9). Four S . typhimurium strains, TA97, TA98, TA100, and TA102 were employed in the Ames tests. The mutagenicity was detected from all three chemicals. The addition of S9 increased the mutation ratios of three chemicals to four strains, except BP-6 to TA100 strain and 4-MBC to TA97 and TA98 strain. In the mixed experiment, all positive effects were detected in the absence of S9. However, the results all became negative in the presence of S9. For the mixture of BP-6 and 4-MBC, positive results were detected on four tester strains except for the TA100 strain. For the mixture of BP-6, BP-8, and 4-MBC, positive results were detected on four strains. The mixture test results showed antagonism in mutagenicity for the mixture of BP-6 and 4-MBC to TA98 and TA100 strains and the mixture of BP-6, BP-8, and 4-MBC to TA100 and TA102 strains.
研究领域:
环境科学
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毒理学
·
生物学
✓ 已验证
DOI
高影响因子
REGULATORY TOXICOLOGY AND PHARMACOLOGY
·
2015
·
IF 2.031
Xin Wu,Dan Wan,Chunyan Xie,Tiejun Li,Ruilin Huang,Xugang Shu,Zheng Ruan,Zeyuan Deng,Yulong Yin
N -carbamylglutamate (NCG) is a metabolically stable analog of N -acetylglutamate that activates carbamyl phosphate synthase-1, a key arginine synthesis enzyme in enterocytes. It is a promising feed additive in swine in China. In this study, we assessed the acute and sub-acute toxicity of NCG in Sprague–Dawley (SD) rats. All rats survived until they were killed at a scheduled time point. No adverse effects or mortality was observed following acute oral administration of 5000 mg/kg NCG to SD rats. No biologically significant or test substance-related differences were observed in body weights, feed consumption, clinical signs, a functional observational battery, organ weights, histopathology , ophthalmology, hematology, coagulation, and clinical chemistry parameters in any of the treatment groups in sub-acute doses of NCG at target concentrations corresponding to 500, 2000, and 3000 mg/kg/day for 28 days neither. In addition, no evidence of mutagenicity or genotoxicity was found, either in vitro in bacterial reverse mutation assay or in vivo in mice bone marrow micronucleus assay and sperm shape abnormality assay. On the basis of our findings, we conclude that NCG is a non-toxic substance with no genotoxicity.
研究领域:
毒理学
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动物营养学
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分子生物学
✓ 已验证
DOI
高影响因子
Foods
·
2023
·Vol. 12
·期 2
·293
·
IF 5.2
Pengbo Wang,Dongman Wan,Ting Peng,Yujing Yang,Xuefang Wen,Xianghui Yan,Jiaheng Xia,Qingwen Zhu,Ping Yu,Deming Gong,Zheling Zeng
Cinnamomum camphoraseed kernel oil (CCSKO) is one of the important natural medium chain triglycerides (MCT) resources, with more than 95.00% of medium chain fatty acids found in the world, and has various physiological effects. However, CCSKO has not been generally recognized as a safe oil or new food resource yet. The acute oral toxicity test and a standard battery of genotoxicity tests (mammalian erythrocyte micronucleus test, Ames test, and in vitro mammalian cell TK gene mutation test) of CCSKO as a new edible plant oil were used in the study. The results of the acute oral toxicity test showed that CCSKO was preliminary non-toxic, with an LD50value higher than 21.5 g/kg body weight. In the mammalian erythrocyte micronucleus test, there was no concentration-response relationship between the dose of CCSKO and micronucleus value in polychromatic erythrocytes compared to the negative control group. No genotoxicity was observed in the Ames test in the presence or absence of S9 at 5000 μg/mL. In vitro mammalian cell TK gene mutation test showed that CCSKO did not induce in vitro mammalian cell TK gene mutation in the presence or absence of S9 at 5000 μg/mL. These results indicated that CCSKO is a non-toxic natural medium-chain oil.Keywords:Cinnamomum camphoraseed kernel oil;acute oral toxicity;genotoxicity assessment;medium chain oil;safety assessment
研究领域:
毒理学
·
食品科学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2013
·
IF 3.01
Jianyong Li,Xiaojun Kong,Xiwang Li,Yajun Yang,Jiyu Zhang
Aspirin eugenol ester (AEE) is a promising drug candidate for treatment of inflammation, pain and fever and prevention of cardiovascular diseases with less side effects and it is important to characterize its genotoxicity. In this study, the genotoxicity of AEE was assessed with two standard genotoxicity assays of the Salmonella typhimurium mutagenicity assay (Ames test) and the mouse bone marrow micronucleus assay. In the Ames test , Salmonella strains TA97, TA98, TA100, TA102 and TA1535 were treated with or without the metabolic activation with a S9 fraction from Acroclor-induced rat liver. The doses of AEE were 5 mg/plate, 2.5 mg/plate, 1.25 mg/plate, 0.625 mg/plate and 0.3125 mg/plate, respectively. In the above tested strains, mutagenicity with or without the S-9 mixture was not detected. In the mammalian erythrocyte micronucleus assay, fifty mice were divided into five groups evenly and the AEE dose at 5000 mg/kg, 2500 mg/kg and 1250 mg/kg and the cyclophosphamide dose at 40 mg/kg as a positive control, the 0.5% of CMC-Na as negative control were administered. The results showed that AEE did not induce any significant increase in micronucleated erythrocytes after 24 h ( p < 0.01). Our results suggested that AEE was non-genotoxic in vivo or in vitro .
研究领域:
药理学
·
毒理学
·
遗传学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Wenwen Luo,Keqi Hu,Yijing Chen,Lin Wang,Yungang Liu
Tris(2-butoxyethyl) phosphate (TBOEP) is an organophosphorus flame retardant ubiquitously present in the environment and even the human body. TBOEP is toxic in multiple tissues, which forms dealkylated and hydroxylated metabolites under incubation with human hepatic microsomes; however, the impact of TBOEP metabolism on its toxicity, particularly mutagenicity (typically requiring metabolic activation), is left unidentified. In this study, the mutagenicity of TBOEP in human hepatoma cell lines (HepG2 and C3A) and the role of specific CYPs were studied. Through molecular docking, TBOEP bound to human CYP1A1, 1B1, 2B6 and 3A4 with energies and conformations favorable for catalyzing reactions, while the conformations of its binding with human CYP1A2 and 2E1 appeared unfavorable. In C3A cells (endogenous CYPs being substantial), TBOEP exposing for 72 h (2-cell cycle) at low micromolar levels induced micronucleus, which was abolished by 1-aminobenzotriazole (inhibitor of CYPs); in HepG2 cells (CYPs being insufficient) TBOEP did not induce micronucleus, whose effect was however potentiated by pretreating the cells with PCB126 (CYP1A1 inducer) or rifampicin (CYP3A4 inducer). TBOEP induced micronucleus in Chinese hamster V79-derived cell lines genetically engineered for stably expressing human CYP1A1 and 3A4, but not in cells expressing the other CYPs. In C3A cells, TBOEP selectively induced centromere protein B-free micronucleus (visualized by immunofluorescence) and PIG-A gene mutations, and elevated γ-H2AX rather than p-H3 (by Western blot) which indicated specific double-strand DNA breaks. Therefore, this study suggests that TBOEP may induce DNA/chromosome breaks and gene mutations in human cells, which requires metabolic activation by CYPs, primarily CYP1A1 and 3A4.
研究领域:
毒理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Jingke Xu,Leina Dou,Sijie Liu,Lihong Su,Xuechi Yin,Jing Ren,Huilan Hu,Daohong Zhang,Jing Sun,Zhanhui Wang,Jianlong Wang
Furazolidone (FZD) and its metabolite called 3-amino-2-oxazolidinone (AOZ) would induce carcinogenic and mutagenic effects to human. In this work, to develop a novel, stable, and simple point of care testing (POCT) with a potential to social applied for FZD detection, we utilized the aspect of protein staining of coomassie brilliant blue (CBB) to exploit a new CBB-LFIA strategy free of NPs. Only one mixing step is needed during the probe manufacturing process, which requires just 2 h and is a great time saving strategy compared with other methods (requiring 4–33 h for probe preparation). Besides, the cost of CBB-LFIA is 300 times lesser than other LFIA with respect to obtaining the label. The developed CBB-LFIA was successfully applied to detect AOZ with a detection limit of 2 ng mL −1 , without any influence from other potential interfering compounds. The proposed CBB-LFIA exhibited prominent practical application, and possesses considerable utilization potential in the related field.
研究领域:
分析化学
·
即时检测
·
食品安全
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cleaner Production
·
2021
·
IF 9.297
Xiaoying Chen,Jianlong Wang
Penicillin G (PG), a frequently detected β-lactam antibiotic in aquatic environment, has attracted extensive concerns because of its extensive application and potential to develop antimicrobial resistance. In this study, gamma radiation was used to degrade PG in water. The main influencing factors, such as initial PG concentration, pH value, absorbed dose, as well as water matrix (inorganic anions and organic matters) were investigated. Results showed that lower initial concentration, acidic condition (pH = 5.57), and higher absorbed dose was conducive to PG degradation. Besides, NO 3 − , HCO 3 2− , SO 4 2− and HPO 4 2− had negative influence on PG degradation, while Cl − had positive influence. Organic matters had negative influence. Twelve transformation intermediate products (TPs) were identified during PG degradation. Together with the density functional theory (DFT) calculation, four possible pathways of PG degradation were proposed. The results of antibacterial activity test demonstrated that the transformation of PG to TPs eliminated the antibacterial activity. Notably, except some para-modified products of PG, the toxicity of other TPs was reduced PG degradation. Moreover, no potential risk of bacterial mutagenicity during PG degradation was observed. In summary, ionizing radiation has good performance in PG degradation in the real wastewater .
研究领域:
环境科学
·
辐射化学
·
药学
·
毒理学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）