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Objective To establish a mouse model for short-term exposure to ambient PM and to investigate the impact on the Cytochrome P450 1A1(CYP1A1)and O6-methylguanine-DNA methyltransferase(MGMT)mRNA expression. Methods Twenty 6-week-old BALB/c mice were randomly assigned to one of two groups, each consisting of 5 male and 5 female animals. These mice were then housed in situ concurrently for 2 weeks in our lab located in urban area of Hangzhou. The first group was kept inside an individual ventilated caging(IVC)system equipped with a high-efficiency particulate-air(HEPA)filter, whereas the second was housed inside a IVC with HEPA filter removed. Then it's allowed flow-through of ambient air freely via a pipeline outside. Mice inside the HEPA filtration chamber were therefore protected from exposure to all airborne particulate. The other was in fact exposed to ambient air directly. After the exposure, the bronchoalveolar lavage(BAL)fiuid was collected for each animal and the differentials and percentages of BAL cells were determined. Paraffin sections of lungs of the mice were made and were examined for any inflammation changes. CYP1A1 and MGMT mRNA levels in the lungs were then detected by RT-qPCR. Results The mean concentration of PM2.5was(99.7±51.6)μg/m3in the exposure group. Weight increases were similar between the two groups(P>0.05). The number of total cells and macrophages in BALF from exposure mice was significantly greater than control.A mild inflammation was observed from light photomicrographs of the lung after PM exposure. CYP1A1 and MGMT mRNA levels were significantly up-regulated in the lung from the exposure group. Conclusion A mouse model for short-term exposure to ambient PM was established. CYP1A1 and MGMT may mediate the toxic effect of PM exposure.
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Objective To investigate teratogenicity on the zebrafish embryo and genetoxicity induced by Sodium Pentachlorophenate (NaPCP),and to provide suggestions for protecting the environmental safety and human health. Methods Zebrafish embryonic development test,p53 gene in zebrafish eggs mutagenicity test,Vicia Faba Micronucleus Test and Ames test were used in the studies.Results The results of zebrafish embryonic development test showed that NaPCP increased embryonic 120 hpf teratogeny rates and 120 hpf death rates and decreased embryonic 120 hpf hatching rates in concentration of 0.5 -2.5 μL/L,with significant teratogenic effect on the embryo.The rates of embryo abnormity increased with the exposure time and concentration.Sequence analysis showed that NaPCP exposure group zebrafish p53 gene had mutated at the concentration of 0.4 μL /L.The base substitution of AAT→AAG at codon 49,ACA→ACG at codon 87 and GCG→GCA at codon 158 were detected by PCR -directed sequencing.This may result in the Asn→Lys of expressed p53 protein.As compared with control group,0.2 mg/L,1.0 mg/L dosage of NaPCP could induce an extremely significant increase in micronucleus frequency of vicia faba root tip cells and had a certain dose -effect relationship.Ames test was negative.Conclusion NaPCP could delay embryonic development and even cause embryonic lethality and induce abnormality in zebrafish.NaPCP had certain genetoxicity.
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Objective To explore the influence of 30 day feeding test of health food containing caffeine on the physiological state of SD rat.Methods SD rats were randomly divided into five groups according weight :three health food containing caffeine(1.64,3.28,6.57 g/kg),one health food containing reduced caffeine (6.48 g/kg)and the control group. Haematological and biochemical parameters were measured at the end of experiment,and main organ tissue analysis was also performed.Results Weight at the end of 4 week,weight after absolute diet,total weight increased,and total food consumption and food consumption at the end of 4 week in 6.57 g/kg groups of male rats were decreased compared with the control group (P <0.05 ).Conclusion In comparison with 6.48 g/kg group,all those changes may be caused by overhigh caffeine in 6.48 g/kg group.
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Objective Toinvestigatethecytotoxicityandoxidativestressofambientfineparticulatematter(PM2.5)and water-solublefractionofPM2.5onhumanbronchialepithelialcells(HBE).Methods PM2.5sampleswerecollected in the urban area of Hangzhou.Then the water-soluble fraction was extracted from PM2.5.After HBE cells were exposed to PM2.5 and its water-soluble fraction at the doses of 0,100,250,500,1 000,1 500 and 2 000 μg/mL for 24 h, CCK-8 (cell counting kit-8 )assay was conducted to examine the cytotoxicity of the PM2.5 and its water-soluble fraction.The oxidative damage induced by PM2.5 and its water-soluble fraction on HBE cells was then evaluated with lipid peroxidation,the superoxide dismutase (SOD ) activity,and the levels of glutathione peroxidase (GSH -Px ). Results ThePM2.5anditswater-solublefractionreducedtheviabilityofHBEcellsinadose-dependentmanner. When the PM concentrations were 200,400 and 800 μg/mL,the SOD activity of the HBE cells decreased significantly,as compared with the control group (P<0.05 ).Also,the malondialdehyde (MDA)levels of the HBE cells significantly increased at the doses of 200,400 and 800 μg/mL (P<0.05).However,there were no significant differences of GSH-Pxactivityamongthegroups.Conclusion ThePM2.5anditswater-solublefractioncouldinducecytotoxicand oxidative damage effects on the HBE cells.
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Objective To learn the toxic effects on rats repeatedly exposed to dichloromethane by dermal route at the same dose for 28 days.Methods Seventy two Sprague Dawley rats were divided into six groups:a solvent control group (oliver oil),four exposure groups (0.75,1.5,3.0 and 6.0 g/kg·BW)and a recovery group.Each group included six female and six male rats.The exposure groups were dermal exposed to DCM at 1.5,3.0 and 6.0 g/kg·BW,6 hours/day,5 days/week for four weeks.The recovery group was dermal exposed to 6.0 g/kg BW of DCMduring the same period then recovered for 2 weeks.Clinical signs including body weight and food consumption of each group were observed.After rats were sacrificed,the hematological and serum biochemical parameters were determined.Histopathological examination was performed on selected tissues for all animals.Results The male rats in test groups including four exposure groups and a recovery group,showed decreased body weight gain.Neutrophilia and lymphocytopenia were determined in females of 3.0 and 6.0 g/kg BW groups and males of 1.5,3.0 and 6.0 g/kg BW groups by blood routine test (P <0.05).The mean levels of serum ALT and AST significantly increased in males of 3.0 and 6.0 g/kg BW groups (P <0.05).Only the mean level of serum TG in males of 6.0 g/kg BW group decreased (P <0.05).No significant differences of these indexes were shown in female rats of all exposure groups compared to control group.The exposure -related significant increases on the incidences of epidermis and dermis lesion,hepatocellular degeneration and necrosis were observed in test groups compared to the control group.The rats of recovery group were exhibited normal percentages of lymphocytes and neutrophils,levels of ALT,AST and TG. The skin and hepatocellular lesion were improved to some extent, but not recovered exactly.Conclusion In a 4 -week repeated -dose toxic study,DCM induce dose -related effects in rats involving skin lesion and liver injury with adverse changes in body weight gain of male rats,part parameters of hematology and serum biochemistry .
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<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of using Jiangzhi Tongluo Soft Capsule (JTSC) combined with Atorvastatin Calcium Tablet (ACT) or ACT alone in treatment of combined hyperlipidemia.</p><p><b>METHODS</b>A randomized, double blinded, parallel control, and multi-center clinical research design was adopted. Totally 138 combined hyperlipidemia patients were randomly assigned to the combined treatment group (A) and the atorvastatin treatment group (B) by random digit table, 69 in each group. All patients took ACT 20 mg per day. Patients in the A group took JTSC 100 mg each time, 3 times per day. Those in the B group took JTSC simulated agent, 100 mg each time, 3 times per day. The treatment period for all was 8 weeks. Serum levels of triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were observed before treatment, at week 4 and 8 after treatment; and safety was assessed as well.</p><p><b>RESULTS</b>At week 4 and 8 after treatment serum TG decreased by 26.69% and 33.29% respectively in the A group (both P < 0.01), while it was decreased by 25.7% and 22.98% respectively in the B group (both P < 0.01). At week 8 decreased serum TG was obviously higher in the A group than in the B group (P < 0.05). Compared with before treatment, serum levels of LDL-C and TC levels decreased significantly in the two groups (all P < 0.01). There was no statistical difference in the drop-out value and the drop-out rate of serum LDL-C and TC levels (P > 0.05). At week 8 the serum HDL-C level showed an increasing tendency in the two groups. No obvious increase in peptase or creatase occurred in the two groups after treatment.</p><p><b>CONCLUSION</b>JTSC combined with ACT could lower the serum TG level of combined hyperlipidemia patients with safety.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Atorvastatin , Double-Blind Method , Drug Therapy, Combination , Drugs, Chinese Herbal , Therapeutic Uses , Heptanoic Acids , Therapeutic Uses , Hyperlipidemias , Drug Therapy , Pyrroles , Therapeutic Uses , Treatment Outcome , Triglycerides , BloodABSTRACT
<p><b>OBJECTIVE</b>To explore the feasibility of transfecting recombinant Sp1 into hypertrophic scar fibroblasts and investigate the proliferation and collagen I, III synthesis in the transfected cells.</p><p><b>METHODS</b>Recombinant human Sp1 was transfected into hypertrophic scar fibroblasts with the karyocyte expressive vector. The expression of Sp1, collagen I, III mRNA was tested by real time PCR. The change of cell proliferation was observed with CCK8 colorimeter.</p><p><b>RESULTS</b>About 30% of transfected hypertrophic scar fibroblasts showed green fluorescence positive. The relative expression of Sp1 mRNA in transfected cells, empty-vector cell or untransfected cells group was 5.26 +/- 0.76, 1.08 +/- 0.18, 1.09 +/- 0.15, respectively, showing a significant difference between thansfected and untransfected cells or between the transfected cells and empty-vector group (P <0.01, n = 5). Expression of collagen I, III mRNA was 2.49 +/- 0.40 and 1.88 +/- 0.30 in transfected cells, 0.96 +/- 0.18 and 0.95 +/- 0.18 in empty-vector cell, and 0.97 +/- 0.15 and 0.93 +/- 0.13 in untransfected cells, respectively, showing a significant difference between thansfected and untransfected cells or between the transfected cells and empty-vector group (P < 0.01, n = 5).</p><p><b>CONCLUSIONS</b>The hypertrophic scar fibroblasts could be as the target cells of Sp1 gene transfection. Sp1 gene may play an important role in abnormal collagen metabolism in hypertrophic scar.</p>