scholarly journals Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Zhong Han ◽  
Jianmin Guo ◽  
Feibiao Meng ◽  
Haifeng Liao ◽  
Yinghua Deng ◽  
...  

Introduction. Forsythin is the main ingredient of Forsythia suspensa and is widely used in treatment of fever, viral cold, gonorrhea, and ulcers clinically. This study aimed to evaluate the potential genetic toxicity of forsythin and its safety for human use. Methods. Based on the Good Laboratory Practice regulations and test guidelines, the genetic toxicity of forsythin was assessed by the Ames test, chromosome aberration (CA) test, and bone marrow micronucleus (MN) test in vivo. In the Ames test, five strains of Salmonella typhimurium were exposed to different concentrations of forsythin in the presence or absence of the S9 mixture, and then, the number of His + revertant colonies was counted. In the CA test, Chinese hamster lung (CHL) fibroblast cells were treated with different concentrations of forsythin, mitomycin C, or cyclophosphamide in the presence or absence of the S9 mixture, and the chromosomal aberrations were determined. In the MN test, bone marrow was isolated from the mice with different treatments, and the ratios of polychromatic erythrocytes (PCE) and erythrocytes (PCE/(PCE + NCE)) were measured. Finally, beagle dogs were divided into four groups (negative control, low dose, medium dose, and high dose groups), and then, a telemetry system was used to evaluate the safe use of forsythin. Results. Ames test results showed that the number of colonies in all test strains with different treatments showed no significantly dose-dependent increase in the presence or absence of the S9 mixture ( p > 0.05 ). In the CA test, the number of cells with aberrations in the CHL fibroblast cells treated with low, medium, and high doses of forsythin for 24/48 h in the absence of the S9 mixture was, respectively, 5.0/2.5, 4.5/1.5, and 5.0/5.0, and in the presence of the S9 mixture, the number was, respectively, 5.0, 5.0, and 4.5. These results showed that there was no significant difference compared to the negative control group either in the presence (2.0) or in the absence (4.0/2.5 for 24/48 h) of the S9 mixture ( p > 0.05 ). The MN test showed that the values of PCE/(PCE + NCE) in the negative, positive controls, and forsythin treatment groups were all more than 20%, which indicated that forsythin had no cytotoxicity. Additionally, no significant toxicological effects of forsythin on blood pressure, respiration, temperature, electrocardiogram, and other physiological indicators in the conscious beagle dogs of different groups were observed by the telemetry method. Conclusion. Our findings showed that forsythin has low probability of genetic toxicity and no significant toxicological effects, which implied that forsythin is suitable for further development and potential application.

2009 ◽  
Vol 25 (7) ◽  
pp. 467-471 ◽  
Author(s):  
BN Mojidra ◽  
K. Archana ◽  
AK Gautam ◽  
Y. Verma ◽  
BC Lakkad ◽  
...  

Pan masala is commonly consumed in south-east Asian and other oriental countries as an alternate of tobacco chewing and smoking. Genotoxic potential of pan masala (pan masala plain and pan masala with tobacco known as gutkha) was evaluated employing chromosome aberration (CA) and micronucleus (MN) assay in vivo. Animals were exposed to three different doses (0.5%, 1.5% and 3%) of pan masala plain (PMP) and gutkha (PMT) through feed for a period of 6 months and micronucleus and chromosomal aberrations were studied in the bone marrow cells. Induction of mean micronuclei in polychromatic erythrocytes (MNPCE) and normochromatic erythrocyte (MNNCE) was higher in both types of pan masala treated groups with respect to control group. Both pan masala plain and gutkha treatment significantly induced the frequency of MNPCE and MNNCE in the bone marrow cells, indicating the genotoxic potential. Furthermore, slight decline in the ratio of polychromatic erythrocytes to normochromatic erythrocytes was also noticed, suggesting the cytotoxic potential even though the ratio was statistically non significant. A dose-dependent, significant increase in chromosome aberration was observed in both types of pan masala treated mice with respect to control. However, no significant difference in micronucleus and chromosomal aberration induction was noticed between two types of pan masala exposed (PMP and PMT) groups. Results suggest that both types of pan masala, i.e. plain and gutkha, have genotoxic potential.


2011 ◽  
Vol 183-185 ◽  
pp. 905-909
Author(s):  
Miao Yu ◽  
Yu Bin Ji

Study on whether genetic toxicity of toluene diisocyanate (TDI) is reversible. This paper detected Chromosomal aberrations and content of RNA & DNA. Chromosome aberration rate and the RNA/DNA ratio of TDI 1/4LC50 and 1/2 LC50 dosing exposure group were higher than negative control group significantly (P<0.01). There was no significant difference between 1/4LC50 and 1/2LC50 (P>0.05).The results showed that the damage of TDI on chromosomes and DNA was repairable, but can not be repaired completely.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5420-5420
Author(s):  
Jianyu Weng ◽  
Xin Huang ◽  
Xiaomei Chen ◽  
Qiong Luo ◽  
Jianhua Su ◽  
...  

Abstract Background: Our preliminary research found that STAT3, IL-17A, and IL-21 expressed in cGVHD patients. So, we provide the blocking STAT3 signal to the induction of Treg cells differentiation, and to provide experimental basis on new targets of cGVHD immunotherapy. Methods: 1. Mice spleen CD4+ CD62L+ naiveT cells were separated by immune magnetic bead and then activated for 72 h. After 96 h infection with STAT3-shRNA and negative control lentivirus, the Th subgroup proportion were measured by flow cytometry. Th related cytokines levels test by Luminex. Real time quantitative PCR was to detect STAT3 and Th subgroup related transcription factor mRNA levels. CD117+ mouse bone marrow stem progenitor cells were sorted by flow cytometry, and transfected by STAT3-shRNA. Inhibition of STAT3 gene in mRNA level was measured at 96 h. Cell proliferation activity was test with CCK8 kit, and cell apoptosis rate determined by flow cytometry. Differentiation of CD117+ cells was induced by 2.2% of methyl cellulose and different cytokines. 2. BALB/c female mice, after the linear accelerator 700cGy of whole body irradiation, accepted miHA mismatched male B10. D2 mice bone marrow cells and spleen cells (8 x 106, 1:1). Randomly assigned 6 mice of cGVHD clinical score of 0.6 or above to each group. After STAT3-shRNA or negative control lentivirus treatment, the observe end point was 58th day after transplantation. The clinical and pathologic scores compared. Th17 and Treg cells measured by flow cytometry. Th related cytokines measured by Luminex. Purpose genes in blood and protein expression levels in target organs were found by Q-PCR and western blot test, respectively. Results: 1. The Th17 / Treg ratio of shRNA group was significantly decreased than that in the NC group (P < 0.05). Except for the Foxp3 gene, other purpose genes, including T-bet, Gata3, RORγt, TGFβ, Notch1, and Jagged2 mRNA levelsin interference group were cut. GM-CSF, IFN-gamma, beta, IL- 3, IL-2, IL-4, IL-6, TNF alpha, IL-17, IL-22a, IL-27, and IL-9 factor expression levels were significant difference between shRNA and negative control group (P < 0.05). There was no significant difference of cell proliferation activity, early apoptosis rate, and differentiation ability in STAT3-shRNA treated CD117+ bone marrow, compared with negative control group and blank control group (P > 0.05). 2. After 50th day, shRNA treatment group appear hair recovery, energy recovery, weight gain, shortness of breath better, mean of cGVHD score decreased. At the 58th day, clinical scores of cGVHD between shRNA treatment group and the negative control group overall mean difference was statistically significant (P < 0.05). cGVHD pathological score of lungs in shRNA treat group reduced (P < 0.05). STAT3mRNA levels in peripheral blood, phosphorylated STAT3, and STAT3 expression level of lung declined than control groups. The proportion of Th17 / Treg cells of spleen was significant reduced in shRNA group, compared with negative control group (P < 0.05). Conclusion: 1. STAT3 knocking down in naïve CD4 + Th cells induced the increased Treg cells, and the decreased Th17 cells. IL-2 confirmed to promote the growth of Treg cells. It speculated that blocking STAT3 might bring Th9 cells differentiation. STAT3 blocking in CD117+ stem progenitor cells have no significant effect on the proliferation, apoptosis and differentiation, validation the safety of STAT3-shRNA. 2. STAT3-shRNA treatment cGVHD mice in vivo achieved curative effect. The main target organs was the lung, which might be closely related to the fall in the proportion of Th17 /Treg. STAT3 may be used as a new target for immunotherapy of cGVHD. Acknowledgment The project was sponsored by grants from National Natural Science Foundation of China (No. 30972790; No.81270648; No.81370665; No.81300446), Provincial Natural Science Foundation of Guangdong (No. S2012010009560), Provincial Science and Technology Planning Project of Guangdong (No.2013B021800186; No.2013B021800201), and Science and Technology Planning Project of Guangzhou (No. 201400000003-4, 201400000003-1). Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Zohre Khodabandeh ◽  
Mahmoud Etebari ◽  
Mehdi Aliomrani

Abstract Background and aim Approximately, 2 million tonnes of pesticides are utilized annually worldwide. Phosalone (Pln), an organophosphorus pesticide, acts as an insecticide and acaricide to control pests of crops such as nuts, citrus fruits, pomegranates, stone fruits, grapes, potatoes, and artichokes. The purpose of this study was to evaluate the possible genotoxic effects following exposure to Pln in the cells derived from mouse red bone marrow. Materials and methods Sixty mice were divided into 6 groups including cyclophosphamide (40 mg/kg, IP) and Pln (6, 12, 20, and 40 mg/kg) exposure by gavage. After 1 and 5 days of exposure, animals were euthanized and the genotoxicity assays were done on bone marrow extracted cells. Results Comet assay shows a time and dose-dependent toxicity which further DNA degradation is observed after 5-day exposure (p < 0.05). Also, Pln significantly increased the MnPCE/PCE ratio after 12 and 20 mg/kg administration while no significant difference was reported between the doses of 6 and 40 mg/kg BW with the negative control group. Conclusion Our results suggested a serious concern about its potential effects on biological life and related disease inductions. However further studies need to confirm the exact mechanism of Pln genotoxicity and the cause of diverse response of its activity at 40 mg/kg. This study also showed that increasing the dose of Pln reduces the MnNCE/Total cells ratio, which may indicate the possibility of bone marrow suppression. All of the above results emphasize the need to seriously limit the use of this compound as an agricultural pesticide.


2019 ◽  
Vol 24 (7) ◽  
pp. 33
Author(s):  
WAGDI SABEEH SADEQ ◽  
SHIREEN ABED AL-RAZAQ TAHA

Genotoxicity and cytotoxicity of Belomycin (BLM) have been evaluated in bone-marroww cells by micronucleus test, as well as the analysis of sperm shape abnormalities in male white mice, considering that BLM is the most wide anticancer drug used with patients. Also, the study includes assessment the effect of crude water and alcoholic extracts of the four o'clock flowers (Mirabilis jalapa Linn) in reducing BLM toxicity and the study was carried out  in the Genetics Laboratory of the Department of biology for the period from 1-10-2017 to 1-5-2019.So the genotoxicity and cytotoxicity were evaluated independently and in conjunction between two different dosages of BLM 0.8 and 1.6 mg.kg-1.bwt. and three orally dosage of different concentration of crud extracts, which is 39.8, 26.52, 13.26 mg.kg-1 and 7.02, 4.68, 2.34 mg.kg-1 o water and alcohol extract respectively. The results of assessment of BLM genotoxic effects showed that the drug caused induction of micronuclei, here were significant increase in micronucleated polychromatic erythrocytes (MNIPCEs) and significant increase in micronuclei(MNI) in the groups treated with 0.8 and 1.6 mg.kg-1 of BLM, compare to negative control at the level of significance P <0.05 On the other hand, the results showed that BLM has potential to induce sperm shape abnormalities, which include head and tail abnormalities, It included an increase in the proportion of morphological abnormalities in the head and tail of the sperm when compared to negative control at the significant level of P <0.05. The results also showed, that treatment with low dosages of four o'clock flower crud extracts didn’t induce neither micronuclei or any increase in PCEs numbers nor sperm shape abnormalities, although some toxic effects do exist with the higher dosages. Evaluation of results from dependent treatments of BLM and different concentrations of water and alcoholic crud extracts, we observed significant role of these extracts in reducing toxic effects of the drug BLM in bone marrow cells, which caused significant decrease in mean differences of MNIPCEs and MNI. More over the results showed significant decrease in mean differences of sperm shape and tail abnormalities compared to negative control. Results of the current study suggest that water and alcoholic four o'clock flower crud extracts have a role in reducing genotoxic and cytotoxic effects of BLM in bone-marrow cells and sperms of white mice   http://dx.doi.org/10.25130/tjps.24.2019.126


Author(s):  
Ajirni Ajirni ◽  
Nazaruddin Nazaruddin ◽  
Amalia Sutriana ◽  
Dian Masyitha ◽  
Muhammad Isa

Burns are caused by heat exposure, such as fire, radiation, electricity or chemicals that can damage the skin and affect the body's systems. The aim of this study was to find out the effect of the ethanol extract of Malacca leaves (Phyllanthus emblica) on the number of fibroblast cells in white rats (Rattus norvegicus) that have burned. This study used 24 white rats (Rattus norvegicus) were divided into 4 groups that smeared with aquadest as a negative control (P1), 5% ethanol extract gel of Malacca leaves (P2), 10% ethanol extract gel of Malacca leaves (P3), and positive control applied with bioplasenton® gel (P4). The IIA degree burn were created by placing a 2x2 cm hot iron plate on the back of the rat for 5 seconds. The euthanasia performed to all animal and the skin samples were collected after 15 days of treatment. Then histopathological preparations were made using HE staining. The number of fibroblast cells were analyzed by ANOVA test. The average number of white rats (Rattus norvegicus) fibroblast cells that suffered burns P1 (negative control) had a number of 7 ± 1.4 cells/visual. Whereas th e P2 group had a number of 4.2 ± 1.58 cells/visual. This value has a significant difference with the negative control. But the P2 and P3 values (3 ± 1.51 cells/visual) there is no significant different with the P4 value (positive control) with an average number of P4 fibroblast cells were 2 ± 0.4 cells/visual. The results of this study concluded that the ethanol extract of malacca leaves 5% and 10% had an effect againts accelerating burns healing in white rats ( Rattus norvegicus).


Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4255-4255
Author(s):  
Jingyuan Li ◽  
Xiaoyu Lai ◽  
Huang He

Abstract Human mesenchymal stem cells(hMSCs) have multiple differentiate potential, and it can differentiate into adipocytes, osteogenic cells, chondrocyte and neural cells et al. It has been reported that telomerase activity in hMSCs is negative, but it is still controversial and telomerase activity in hMSCs-derived adipocytes has not been reported. We investigate the telomerase activity in hMSCs before and after their committed differentiation into adipocytes in vitro and cryopreservation. hMSCs were isolated from normal human bone marrow fellowed by cell culture in DMEM with low glucose containing 10% FBS. The FACS was performed to examine the expression of cell surface molecules and analyze cell cycle of primary hMSCs.Then some of hMSCs were induced to differentiate into adipocytes in vitro by being treated with adipocytic medium fellowed by being stained with oil red O, and the others were cryopreserved in liguid nitrogon for three months. TRAP assay(telomerase repeat amplification protocol assay)was employed to detect telomerase activity in those hMSCs. T293 cells and α-Interferon were analyzed with each test as an additional positive control and negative control respectively. Telomerase activity was expressed as a percentage of the relative telomerase activity (RTA) of the hMSCs relative to the RTA of T293 cells. The results indicated the cells were positive for SH2, SH3, CD90 and negative for CD34, CD45, AC133. It was showed that the majority of primary hMSCs(85%) was at cell cycle of G0/G1 phase and the minority of hMSCs was at S, G2 or M phase. 80% hMSCs was orange adipocytes after they were treated with adipocytic medium for 3–4weeks. Telomerase activity was negative in hMSCs both at the beginning of culture and at the later stages during cell expansion,telomerase activity in hMSCs-passage 1–3(n=10) and hMSCs-passage 4–7(n=9) made no significant difference(1.46±0.83% vs 1.46±0.67%, p=0.99). Cryopreservation did not affect the telomerase activity in hMSCs. Telomerase activity in fresh hMSCs(n=13) and frozen hMSCs(n=6) made no significant difference(1.41±0.44% vs 1.51±1.07%, p=0.64). Telomerase activity in hMSCs-derived adipocytes(n=3) was significantly higher than in hMSCs(n=19)( 11.8±2.52% vs 1.46. ±0.67%, p&lt;0.00001). It is concluded that hMSCs are telomerase-negative, and the stage of culture or cryopreservation does not affect their telomerase activity. After being induced to differentiated into adipocytes, hMSCs telomerase activity is upregulated.


2017 ◽  
Vol 37 (8) ◽  
pp. 859-865 ◽  
Author(s):  
Samira L. Abdalla ◽  
Sônia S. Costa ◽  
Marco Antônio Gioso ◽  
Livia M. Casanova ◽  
Marcela A.S. Coutinho ◽  
...  

ABSTRACT: An aqueous leaf extract of the medicinal species Kalanchoe gastonis-bonnieri (here denominated KGB) has been found to be effective as an antimicrobial agent against canine oral cavity bacteria in in vitro assays. In this study, we investigated the effect of topic oral administration of KGB on the development of dental biofilm in Beagle dogs. The experiments were performed with an experimental group (0.2% of KGB extract), a negative control group (0.9% of saline solution) and a positive control group (0.12% chlorhexidine). Each treatment was sprayed into the oral cavity daily for 28 days. Thirty Beagle dogs with similar characteristics and kept under the same management and diet were used. The measurement of dental plaque and calculus was performed using a computerized analytical method. The phenolic profile of KGB extract was analyzed by HPLC-DAD. KGB extract at 0.2% showed efficacy in controlling the formation of plaque compared to the negative control group, and dental calculus in relation to the negative and positive control groups. A significant difference was observed among these three groups. Peaks attributed to flavonoids and phenolic acids were identified in the HPLC-DAD chromatogram of the KGB extract. The presence of these substances could be related to the activity observed. Our findings demonstrate that treatment with KGB is effective in controlling periodontal disease in dogs, providing new insights into the medicinal properties of this plant. KGB extract has a potential use as a supplemental agent in pharmaceutical products for the prevention of periodontal disease.


2009 ◽  
Vol 55 (2) ◽  
pp. 146-153 ◽  
Author(s):  
Bo Liu ◽  
Jianling Jin ◽  
Yanfei Cheng ◽  
Huaiqiang Zhang ◽  
Peiji Gao

The Ames test has not been very effective in estimating the mutagenicity of histidine-containing samples because external free and (or) protein-bound histidine in these samples would allow the histidine auxotrophs in such test samples to grow more compared with the negative controls that were used as the reference. This could give rise to a false positive.n this study, a modified suspension mutagenicity assay (MS assay) was deveopled. The tester strains were incubated in Luria-Bertani (LB) broth containing different concentrations of traditional Chineses medicines (TCMs) until the declining phase, and the test samples were assayed to be mutagenic or not by observing whether statistically significant differences were demonstrated in the relative reversion frequencies (RRFs) between the negative control groups and the test groups. Collectively, using LB broth as the test medium and comparing the RRFs in the declining phase made this assay less influenced by the presence of histidine in the test samples.The mutagenicity of some TCMs was measured with the MS assay. The results in MS assay were consistent with those in the mammalian bone marrow chromosomal aberration test, which indicated that the MS assay was appropriate to estimate the mutagenicity of samples containing free and (or) protein-bound histidine.


2013 ◽  
Vol 85 (3) ◽  
pp. 955-964 ◽  
Author(s):  
FLAVIO F.V. BORGES ◽  
THIAGO C. MACHADO ◽  
KENYA S. CUNHA ◽  
KARLA C. PEREIRA ◽  
ELSON A. COSTA ◽  
...  

Ethnobotanical surveys of Cerrado native plants show that leaves of Celtis iguanaea (Jacq.) Sargent (Cannabaceae), popularly known in Brazil as “esporão de galo”, are used in folk medicine for body pain, asthma, cramps, poor digestion, urinary infection, kidney dysfunctions, as well as a stimulant and diuretic. This work aimed at evaluating possible C. iguanaea aqueous leaf extract (CALE) cytotoxicity, genotoxicity, and antigenotoxicity using the mouse bone marrow micronucleous test. To assess CALE genotoxicity, Swiss mice were orally treated with three different extract concentrations (100, 300, and 500 mgkg−1). To evaluate its antigenotoxicity, the same doses were used simultaneously with a single i.p. dose of mitomycin C (MMC, 4mg.kg−1). The frequencies of micronucleated polychromatic erythrocytes (MNPCE) were evaluated 24 h and 48 h after administration except for the negative control (24 h). Genotoxicity was evaluated using the frequency of micronucleated polychromatic erythrocytes (MNPCE), whereas cytotoxicity was assessed by the polychromatic and normochromatic erythrocytes ratio (PCE/NCE). The results showed that CALE did not exhibit a significant reduction in the PCE/NCE ratio, neither a considerable increase in the frequency of MNPCE. Nonetheless, CALE reduced bone marrow toxicity (increased PCE/NCE ratio) and decreased the micronuclei frequency induced by MMC. We can conclude that CALE presented no cytotoxic and genotoxic effects, but showed antigenotoxic and anticytotoxic actions under the experimental conditions applied in this study.


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