JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Ruyi Feng,Yanlu Li,Junxia Ma,Yanchao Xing,Yingshan Jiang,Zhongmei He,Ying Zong,Rui Du
Ethnopharmacological relevance Spermatogenic Pill (SP) is a commonly used clinical preparation in the Third Clinical Hospital of Changchun University of Traditional Chinese Medicine. Has accumulated a good reputation for more than a decade. However, because SP is a hospital clinical agent, it has received little extensive attention from researchers, which has led to a systematic lack of basic research on it. Therefore, it is impossible to determine whether there are safety hazards that may limit its widespread clinical application, and an in-depth toxicological evaluation of SP is essential and urgent. Aim of the study The aim of this study was to assess the safety of SP by conducting acute and subacute toxicity examinations. Materials and methods Identify active compounds contained in SP by LC-MS, and determination of inorganic elements in SP using ICP-MS. The in vivo acute toxicity of SP was assessed over a duration of 14 days following administration at doses of 7.5, 15, or 30 g/kg. To evaluate subacute toxicity, mice were administered daily doses of SP (7.5, 15, or 30 g/kg) for a period of 28 days. After the treatment period, the animals were euthanized, and standard blood tests, liver and kidney function tests, as well as tests related to glycolipid metabolism, were performed. The principal organs of the mice were collected to calculate organ coefficients and undergo hematoxylin-eosin (HE) staining. Results LC-MS analysis showed that the active components of SP include Quercetin, Kaempferol, Beta-sitosterol, Stigmasterol, Diosbulbin B, Schizandrin, Naringenin, 2,3-hydroxycinnamic acid, L-proline, Histidine and Pluviatolide. The total amount of detected inorganic elements accounted for 3.0919% of SP. During the SP acute toxicity experiment, the groups that received the drug exhibited no signs of adverse reactions or poisoning symptoms. In subacute toxicity experiments, drug-treated mice showed overall favorable status, but the effects of continuous administration of the 30 g/kg group on body weight and food intake were reduced. An increase in the white marrow of spleen tissue after long-term administration of the drug treatment was also observed, suggesting that the drug can increase the maturation process and the number of mature lymphocytes in the spleen, and improve the lymphocyte immunity and humoral immunity function of the organism. Suggests that possibly this should be taken into account in clinical application. The routine blood examinations, as well as the assessments of liver and kidney functions, and the tests for glucose and lipid metabolism, did not reveal any notable toxic effects. Conclusion SP contains more flavonoids, and terpenoid active ingredients, and is non-toxic in the body. This discovery not only strengthens the safety foundation of its clinical application, provides a solid scientific basis for the establishment of reasonable clinical dosage and the implementation of effective clinical toxicity monitoring, but also further lays a solid theoretical cornerstone for the subsequent clinical drug trials.
研究领域:
药理学
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毒理学
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中医药学
✓ 已验证
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2017
·
IF 1.74
Feng Li,Yijia Li,Qingxian Li,Xianai Shi,Yanghao Guo
The interest focusing on Eriobotrya japonica leaf triterpene acid (ELTA) has increased recently because of its beneficial effects on health. However, there has been a lack of experimental data on its toxicity. The present study therefore was conducted to evaluate its toxicity in ICR mice. The results showed that ELTA produced neither mortality nor toxicity of the main organs in ICR male and female mice in both acute (0.30, 0.65, 1.39, and 3.00 g·kg−1 body weight) and subacute (150, 300, and 600 mg·kg−1 BW) 28-day toxicity studies. Because of lacking apparently adverse effects found in the hematology, clinical biochemistry, and histopathology evaluation, results of the present study together with the beneficial effects make ELTA as a promising dietary supplement and indicated that ELTA administered orally might have a large safety margin for human.
研究领域:
药理学
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
REGULATORY TOXICOLOGY AND PHARMACOLOGY
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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
REGULATORY TOXICOLOGY AND PHARMACOLOGY
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2016
·
IF 2.227
Xin Liu,Liangqing Zheng,Rong Zhang,Gang Liu,Shensheng Xiao,Xiaoting Qiao,Yongning Wu,Zhiyong Gong
Nε-(carboxymethyl)lysine (CML) as a novel potential noxious compound in various food products has aroused extensive concern in recent years. This study aimed to investigate the oral acute and subacute toxicity of CML in mice as per OECD 420 and 407 guidelines. Acute administration of 2000 and 5000 mg/kg CML did not induce any mortality within 14 days, nevertheless some toxicological symptoms and histopathological changes were observed. The estimated LD 50 of CML was >5000 mg/kg. In subacute toxicity test , CML was dosed at 200, 500 and 1000 mg/kg in both genders for 28 days. The body weights reduced which was accompanied with the decrease of food consumptions. Hematology parameters viz. RBC , HGB and MCH showed minor alteration but these were still within normal range. Biochemical analysis of hepatic and renal function markers showed significant elevating in AST , ALT , Cr and BUN etc. Histopathological alterations were observed in lung, liver, kidney and spleen. Subacute toxicity of CML involved oxidative stress caused by reducing antioxidant enzyme (SOD and GSH-Px) activities, and significantly increasing lipid peroxide (MDA) level. In conclusion, CML was unlikely to present an acute hazard, but repeated administration could produce deleterious effects on mice especially inducing liver and kidney damage through oxidative stress.
研究领域:
毒理学
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食品科学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Environmental Science-Water Research & Technology
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2022
·Vol. 8
·期 3
·586-596
·
IF 5.819
Zhiquan Li,Congwei Luo,Fengxun Tan,Daoji Wu,Xuedong Zhai,Shishun Wang,Xiaoxiang Cheng,Fumiao Zhang,Mingli Li,Qiao Ma
As an endocrine disruptor, bisphenol A (BPA) is a severe threat to human health. In this study, nitrate (NO3−) photolysis with a low-pressure UV lamp (LP-UV) was employed to degrade BPA in different aqueous solutions. Results showed that BPA could be decomposed efficiently in the UV/NO3− process. Moreover, the contributions of UV irradiation (4.1%), ˙OH (52.7%), and reactive nitrogen species (43.2%) were obtained. The observed rate constant of BPA degradation (kobs) increased with NO3− concentration since more active species were generated in high NO3− concentration. The BPA degradation rate was significantly accelerated as the pH value rose. This was ascribed to the increase of the molar absorption coefficient and the amount of ionic BPA under alkaline conditions. kobs declining with increasing BPA concentration resulted from the inner filter effect and the competition of more generated intermediate products. The increasing kobs with the addition of HCO3−/CO32− (0–10 mM) was explained as the accumulation of ˙NO2 in the presence of HCO3−/CO32− in UV/NO3− process. The effect of Cl− (0–20 mM) could be ignored in this study, which suggested that reactive chlorine radicals degraded BPA effectively. The kobs reduced acutely when NOM (0–5 mgC L−1) existed in the solution, and this could be ascribed to the dual roles of the NOM inner filter effect and reactive radical scavenging effect. Further, several degradation products were detected, and possible transformation pathways were put forward. Remarkably, the acute toxicity of BPA was slightly enhanced then decayed in the UV/NO3− process.
研究领域:
环境科学
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化学工程
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毒理学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Pharmacology
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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
Current Drug Delivery
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2022
·Vol. 20
·期 10
·1559-1568
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IF 3.758
Yang Qingyun,Zhao Chuncao,Yang Jian,Zhao Jingyi,Feng Yi,Liu Minchen,Zhang Jiquan
Background: Rhodojaponin III (RJ-III), a characteristic diterpene of Rhododendron molle G. Don, has a wide range of pharmacological activities including anti-inflammatory, antihypertensive, and analgesic effects. However, further research and development have been limited because
of its intense acute toxicity and poor pharmacokinetic profile. Objective: In this study, we propose the construction of folic acid–conjugated mesoporous silica nanoparticles (FA-MSNs) as carriers to deliver RJ-III in an attempt to reduce acute toxicity and improve biomedical applications
by prolonging drug release and targeting delivery. Methods: FA-MSNs were synthesized and characterized. RJ-III was then loaded into FA-MSNs (RJIII@ FA-MSNs), and the in vitro drug release profile was assessed. Subsequently, the RJ-III@FAMSNs’ cytotoxicity and targeting efficiency
were explored in lipopolysaccharide-activated RAW 264.7 cells, and their acute toxicity was investigated in mice. Results: Spherical FA-MSNs were approximately 122 nm in size. Importantly, the RJ-III@FA-MSNs showed prolonged RJ-III release in vitro. Moreover, in lipopolysaccharide-activated
RAW 264.7 cells, RJ-III@FA-MSNs not only reduced the cytotoxicity of RJ-III (P < 0.01), but also showed a good targeting effect from the results of cellular uptake. Additionally, the acute toxicity results demonstrated that RJ-III@FA-MSNs improved the LD50 value of RJ-III
in mice by intraperitoneal injection 10-fold. Conclusion: This is the first study to use FA-MSNs as carriers of RJ-III to reduce the acute toxicity of RJ-III. The results confirm the potential for targeted delivery of RJ-III in inflammatory cells to enhance efficacy, as well as providing
data for future investigations on anti-inflammatory activity.
研究领域:
药剂学
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毒理学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2013
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IF 3.925
Ruijuan Qu,Xinghao Wang,Zhengtao Liu,Zhenguang Yan,Zunyao Wang
Cadmium (Cd) compounds are widely distributed toxic environmental and industrial pollutants, and they may bring danger to growth and development of aquatic organisms. The effects of Ca 2+ (as CaCl 2 ), Mg 2+ (as MgSO 4 ), K + (as KCl), pH and complexants (EDTA, the commercial DOM , and three homemade DOMs) on Cd toxicity to Photobacterium phosphoreum were evaluated in standardized 15 min acute toxicity tests . Increases in Ca 2+ concentration resulted in higher EC 50 values, indicating the competition between the two ions for uptake sites at the biotic ligand. Increased waterborne Mg 2+ also reduced Cd toxicity, but to a slightly lesser degree compared with Ca 2+ . The overall decline in EC 50 data with increasing K + in test solutions suggested that Cd toxicity was enhanced at larger K + concentration. The toxicity alleviation by H + was observed over the tested pH range of 5.0–9.0. Additions of complexing agents into the exposure water reduced Cd bioavailability via complexation of Cd 2+ , and complexants from different sources displayed different protective effect. The influence of these toxicity modifying factors was finally incorporated into a model that can predict acute cadmidum toxicity for Photobacterium phosphoreum . After validation with laboratory and natural waters, the developed model could support efforts to improve the ecological relevance of presently applied risk assessment procedures.
研究领域:
环境科学
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
TOXICON
·
2024
·
IF 2.6
Xuelin Chen,Kun Zhang,Hanlei Wang,Xia Zhao,Yumei Zhang
Kochiae Fructus (KF) is a traditional Chinese medicine, which has been used to delay aging and treat inflammation, such as rubella, eczema, cutaneous pruritus, etc . In order to fully understand the traditional medicinal value of KF, we evaluated the antioxidant properties and oral safety of its ethanolic extract. Considering flavonoids and phenolics in medicinal plants generally have strong antioxidant activity, we firstly detected the total flavonoids and phenolics contents of KFEE and its fractions. Secondly, we evaluated the antioxidant activities of KFEE and its fractions. Finally, we evaluated the oral safety of KFEE by the acute and 28-day subacute toxicities. The n-butanol fraction (ENBF) possessed the highest phenolics and flavonoids with values of 77.30 ± 3.17 mg gallic acid equivalents/g and 228.81 ± 7.56 mg rutin equivalents/g, respectively. The results of antioxidant tests showed that ENBF possessed potent antioxidant ability. Among them, the high antioxidation capacity observed in ENBF could be attributed to its rich content of flavonoids and phenolics. The results of toxicological studies showed that the LD 50 value of KFEE was 6000 mg/kg BW, and the no observed adverse effect level (NOAEL) of KFEE was 600 mg/kg BW. According to the standards of the American Academy of Sciences for the classification of toxic substances, KFEE can be classified as practically non-toxic substance, which provided valuable evidence for the oral safety of KF as a natural aging delay medicine.
研究领域:
中药学
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药理学
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毒理学
·
天然产物
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 3
·e70075
·
IF 3.4
Xuefeng Qu,Qinxi Wang,Zemi Xie,Yuejin Wu,Yangjunna Zhang,Zhen Liu,Yin Wang
The Chlamydomonas reinhardtii (red) is a strain rich in protoporphyrin IX, which could be used as algal-derived novel sustainable nutritional sources. However, the safety research on C. reinhardtii (red) remains insufficient and further investigation is needed. In order to assess the safety of C. reinhardtii (red) and to expand its use in food applications, a series of toxicological safety evaluations were carried out to observe acute toxicity, subchronic toxicity and genotoxicity of C. reinhardtii (red). The C. reinhardtii (red) was administered to an acute oral toxicity test, mammalian micronucleus test, mouse chromosomal aberration test in Institute of Cancer Research (ICR) mice, and 90-day repeated-dose oral toxicity test in Sprague-Dawley (SD) rats. In the acute oral toxicological test, no mortality or abnormalities were observed in male and female rats, with an median lethal dose(Lethal Dose, 50%) (LD 50 ) exceeding 10.0 g/kg body weight (BW). Similarly, male and female mice exhibited no mortality or abnormalities, with an LD 50 surpassing 20.0 g/kg BW. The results of bacterial reverse mutation test, mammalian micronucleus test, and mouse chromosomal aberration test were all negative, suggesting that the C. reinhardtii (red) did not show mutagenicity under the conditions of this experiment. In a 90-day repeated-dose oral toxicity study, the SD rats were orally administered daily doses of 2.0 g/kg BW, 4.0 g/kg BW, and 8.0 g/kg BW without exhibiting any signs or symptoms of toxicity. Therefore, the no observed adverse effect level (NOAEL) of C. reinhardtii (red) was 8.0 g/kg BW/day. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food. Practical Application The aim of this study was to assess the safety of C. reinhardtii (red) and to expand its use in food applications. The major finding of this study is that the C. reinhardtii (red) did not show acute toxicity, subchronic toxicity and genotoxicity under the conditions of this experiment. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food.
研究领域:
毒理学
·
食品安全
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2019
·
IF 2.697
Xianliang Yi,Tongtong Chi,Bei Liu,Chenxi Liu,Guanqun Feng,Xinyu Dai,Keke Zhang,Hao Zhou
Given the absorbability of nZnO and its inevitable coexistence with trace metals such as Cd and Pb in coastal environment, nZnO can adsorb these pollutants thereby affecting their distribution in different media of marine ecosystem. The marine copepod Tigriopus japonicus was applied in the present study to investigate the combined effect of nZnO and Cd or Pb on mortality and reproduction in marine organisms. For acute exposure, presence of 1.0 mg/L nZnO increased the toxicity of both Cd and Pb, as their LC 50 decreased from 5.9 and 75.4 mg/L to 3.95 and 48.0 mg/L, respectively. For 21 d chronic exposure, the reproduction of the copepod was influenced by Cd and Pb at environmental relevant concentrations, and the interaction between nZnO and Cd or Pb appeared to be antagonistic. The waterborne Cd and Pb concentration was affected by nZnO for neither acute nor chronic exposure, indicating no adsorption of these two metals to nZnO at relative low concentration. The overall findings of this study suggested the binary exposure to nZnO/Cd or nZnO/Pb might have potential different toxic mechanisms between acute and chronic exposure.
研究领域:
环境科学
·
毒理学
·
海洋生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
·
IF 3.69
Hailin Long,Xuehong Qiu,Li Cao,Guiqing Liu,Zhongchen Rao,Richou Han
Ethnopharmacological relevance The Chinese cordyceps, a parasitic Thitarodes insect- Ophiocordyceps sinensis fungus complex in the Qinghai-Tibet Plateau, is one of the most valuable traditional Chinese medicines and health food for ameliorating conditions associated with aging and for treating fatigue, night sweats, hyperglycemia, hyperlipidemia, respiratory, renal and liver diseases, and hyposexuality. The natural Chinese cordyceps resource is rare due to its harsh growing environment, limited geographical distribution and global climate warming. Artificial cultivation of Chinese cordyceps has been successfully established to meet its high demand in market. Aims of the study The present study aims to evaluate the toxicological safety of the cultivated Chinese cordyceps and provide scientific data for subsequent development and utilization of this valuable biological resource. Materials and methods The Chinese cordyceps was cultivated by mimicking the habitat environment in low-altitude areas and identified by morphological and microscopic characteristics. Its phytochemical profile was determined by the HPLC. Toxicological studies based on the cultivated Chinese cordyceps were conducted, including chromosomal aberration test of Chinese hamster lung (CHL) cells, Ames test, acute toxicity test and micronucleus (MN) test of bone marrow cells. Results The Chinese cordyceps successfully cultivated in low-altitude areas exhibited the same morphological and microscopic characteristics as natural Chinese cordyceps. The adenosine content was in accordance with the Chinese Pharmacopoeia (2015 Edition). The HPLC fingerprint was determined and five main chromatographic peaks representing uracil, uridine, inosine, guanosine and adenosine were identified. No dose-dependent increase in the rates of chromosomal aberration was detected in the presence or absence of metabolic activation system. Ames test also demonstrated no dose-dependent increase in the number of reversion mutation for five bacterial strains, with or without rat liver microsomal enzyme mixture (S9) metabolic activation, at a quantity range of 128–5000 μg cultivated Chinese cordyceps per plate. The acute toxicity test with mice showed that after 20 g/kg oral administration of cultivated Chinese cordyceps, neither animal death nor any abnormal change in general dissection of various tissues and organs of the animals were found within 14 days. The median lethal dose (LD 50 ) was greater than 5 g/kg, which is regarded as a non-toxic level, and maximum tolerable dose (MTD) of cultivated Chinese cordyceps in ICR mice was more than 20 g/kg. MN test of mouse bone marrow cells indicated no significant differences among each sample dose and the negative control. Conclusion Based on the results from four toxicological tests, it was concluded that the cultivated Chinese cordyceps was classified as non-toxic in one single administration at high doses by intragastric route in mice. This study provides scientific experimental basis for its safety.
研究领域:
药理学
·
毒理学
·
传统中药研究
✓ 已验证
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）