Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mic...Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mice,Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0,540,1 620,and 6 480 mg/kg in SD rats.Results: In the acute toxicity study,mortality was not observed after 14 days,In addition,clinically relevant adverse effects,or variations in body weight or food consumption were not observed,Similarly,after 30 days in the sub-chronic toxicity study,no mortality or significant toxicological effects such as decreased food consumption,body weight,biochemical parameters and vital organs etc,were noticed,Conclusion: The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration,and therefore is suitable for further development and applications.展开更多
Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of t...Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F<sub>6</sub> was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> for 28 days at a dosage of up to 800 mg/kg did not induce t展开更多
Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was ca...Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was calculated in mice using Dixon＇s up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET（30, 90 and 150 mg/kg） each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result： LD_（50） was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET（P〉0.05）. In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group（P〉0.05）, however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions： The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.展开更多
OBJECTIVE:To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules(清肺达原颗粒,QFDY),and to evaluate the acute and sub-chronic toxicity of QFDY.METHODS:Anti-inflammatory effects were evaluat...OBJECTIVE:To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules(清肺达原颗粒,QFDY),and to evaluate the acute and sub-chronic toxicity of QFDY.METHODS:Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice.Ear swelling degree was calculated and tumor necrosis factor-α,interleukin-1βand interleukin-6 were determined.Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor.Latent period cough and number of cough within 3 min were counted.In acute toxicity study,the rats were randomly divided into test group and solvent control group.Body weighs,food intakes and general clinical signs were monitored.In the sub-chronic toxicity study,QFDY was administered to rats at 0,4,8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted.Mortalities,clinical signs,body weight changes,food intakes,ophthalmological examinations,hematological parameters,biochemical indicators,electrolyte indicators,urinalyses and histopathological examinations were monitored.RESULTS:QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor.The results presented a dose-effect relationship.In acute toxicity study,no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period.In the sub-chronic toxicity study,higher reticulocyte count,lymphocyte and lower Cl-,blood urea nitrogen were analyzed compared with the solvent control group.But the differences were considered to be incidental and not clinically toxic.Obvious dose-effect relationship of urine color was observed,and the three test groups at the end of the experiments resulted in significant increase in urobilinogen,bilirubin,ketone body and urine leukocyte.However,all the positive indicators returned to normal in the recovery period.Therefore,no toxicological changes were found during the study period.CONCLUSION:QFDY showed significant anti-inflammatory and anti-tussiv展开更多
Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the eff...Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the effects of 90 days of oral administration of Datura stramonium(DSE)leaf extract in Rats.Methods:In the oral acute toxicity study,mice were treated with a single oral gavage of DSE at 500,1000,and 2000 mg·kg^(-1)/d,po and observed for signs of acute toxicity for 14 days.In the sub-chronic study,rats were randomized into four Groups(A-D).Group A received distilled water(10 mL·kg^(-1),po)while groups B-D received DSE(10,50 and 250 mg·kg^(-1)/d,po,respectively)orally for 90 days uninterrupted.Animals were weighed weekly,with food and water measured daily and relevant parameters assayed at the end of the 90days administration.Results:In acute toxicity studies,oral administration of up to 2 g·kg^(-1)/d,po of DSE did not elicit any semblance of toxicity or mortality within 24 h to 14 days.In the 90days studies,DSE(250 mg·kg^(-1)/d,po)decreased the body weight,brain weight,and food intake in female rats.DSE(10-250 mg·kg^(-1)/d,po)increased the red blood cell(RBC),packed cell volume(PCV)and hemoglobin(Hb)in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the triglycerides(TG),cholesterol and low-density lipoprotein(LDL);and decreased HDL in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the white blood cells(WBC)and platelets in female rats.DSE(10-250 mg·kg^(-1)/d,po)decreased the alkaline phosphatase(ALP)and alanine transaminase(ALT)in both studies.Serum urea level was decreased in both sexes.DSE(250 mg·kg^(-1)/d,po)decreased male rats’serum sodium ion levels.Liver,brain,testes and kidney showed severe lesions at 250 mg·kg^(-1)/d,po of the extract.Conclusion:D.stramonium is safe on acute exposure and relatively safe on sub-chronic oral administration.How-ever,prolonged use,especially at high doses,could cause Liver,brain and kidney toxicities;and abnormal lipid metabolism.展开更多
Objective To explore the possible long‐term health effects of the defoamer used in seawater desalination by sub‐chronic toxicity testing. Methods Blood analysis, internal organ assessment, and histopathological exam...Objective To explore the possible long‐term health effects of the defoamer used in seawater desalination by sub‐chronic toxicity testing. Methods Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high(0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration. Results The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase(P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin(P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups(P < 0.05). All dose groups showed significant induction of alkaline phosphatase(P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices. Conclusion Long‐term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.展开更多
Objective To investigate the effect of Lead (Pb) acetate exposure on Semliki forest virus (SFV) pathogenesis in mice. Methods Different doses (62.5, 125, 250 and 500 mg/Kg body weight) of Pb dissolved in normal saline...Objective To investigate the effect of Lead (Pb) acetate exposure on Semliki forest virus (SFV) pathogenesis in mice. Methods Different doses (62.5, 125, 250 and 500 mg/Kg body weight) of Pb dissolved in normal saline were given to mice by oral intubation in a sub-acute (28 days) and sub-chronic (90 days) regimen followed by SFV infection. Morbidity, mortality, clinical symptoms, mean survival time (MST), changes in body and organ weight, accumulation of lead in soft tissues, virus titre in brain and histopathological alterations were compared between lead exposed and infected groups. Results Early appearance of virus symptoms, increased mortality, decreased MST, enhanced SFV titre and greater tissue damage were observed in lead exposed-SFV-infected mice. Conclusion Pre-exposure to lead increases the susceptibility of mice towards SFV infection. Further studies are suggested in view of the persistence of lead in the environment and the possibility of infection by microbial pathogens.展开更多
In current study toxicological profile of a commonly used herbal formulation was evaluated that is used extensively for gynecological disorders like menorrhagia, metrorrhagia, leucorrhea, irregular menstrual cycle, pr...In current study toxicological profile of a commonly used herbal formulation was evaluated that is used extensively for gynecological disorders like menorrhagia, metrorrhagia, leucorrhea, irregular menstrual cycle, pre-menstrual syndrome and post-menopausal bleeding. It was also claimed to strengthen endometrium and ovaries. Since this herbal formulation was been used by a large number of population hence there was a need to assess acute and sub-chronic toxicity. Acute oral toxicity (LD50) was observed in albino mice using standard protocols whereas sub-chronic, hematological and histopathological studies were assessed on 24 albino rabbits after giving herbal formulation for 60 days in two doses (20 and 60 mg/kg) against control groups. The outcomes of present study showed that the drug is safe up to 5000 mg/kg following acute oral toxicity test and no mortality was observed during sub chronic toxicity studies. Results of sub-chronic toxicity did not show any significant changes in biochemical, hematological and histopathological parameters. However, some indicators such as urea, creatinine, hemoglobin, and RBC count were altered, but these changes do not correlate with the histopathological results and may be associated to intra individual variations. Despite the safety of the drug in few animals, clinical trials and more investigations on a large number of animals are essentially needed to establish safety and efficacy of the herbal formulation.展开更多
[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17...[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.展开更多
Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After ...Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent.展开更多
A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and...A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg aluminum chloride （AlCl3） per kilogram body weight in drinking water for 120 days. Kidney coefficient and aluminum （Al） concentrations in blood and kidney were determined, and renal autopsy and histological changes were observed. The results showed that kidney coefficient in all Al-treated groups were obviously lower than that in GC （P〈0.01） and there was a dose-effect relationship. The kidneys were solid, lusterless and pale brown with white necrosis point on surface. Under electron microscope, renal cortex became thin, the renal tubule was narrowed and the epithelium dissolved; the renal glomerulus became atrophied and the glomerular became vasodilator. The Al concentrations in blood and kidney were higher in all Al-treated rats than those in GC （P〈0.01）, and there was a dose-effect relationship. The results indicated that sub-chronic Al exposure could lead to Al accumulation in kidney, restrain the development of kidney and cause the pathologic damage in rats.展开更多
Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an ac...Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups.The outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic indicators.The benchmark dose(BMD)approach was applied to estimate the POD.Results Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group.Importantly,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.展开更多
Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establi...Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.展开更多
基金supported by the Basic Science Research Program of Guangdong Province Science and Technology Plan Projects Fund[grant numbers:2016A010119136]the High-level Leading Talent Introduction Program of GDAS[grant numbers:2016GDASRC-0104]
文摘Objective: To access the toxicity of forsythin from Forsythia suspensa leaves and evaluate its safety,Methods: Acute toxicity was determined by oral administration of a single dose of 18 100 mg/kg forsythin in NIH mice,Sub-chronic toxicity was evaluated by oral administration of several doses of forsythin for 30 days at does of 0,540,1 620,and 6 480 mg/kg in SD rats.Results: In the acute toxicity study,mortality was not observed after 14 days,In addition,clinically relevant adverse effects,or variations in body weight or food consumption were not observed,Similarly,after 30 days in the sub-chronic toxicity study,no mortality or significant toxicological effects such as decreased food consumption,body weight,biochemical parameters and vital organs etc,were noticed,Conclusion: The results revealed that the forsythin from Forsythia suspensa leaves has low or no toxicity via oral administration,and therefore is suitable for further development and applications.
文摘Bridelia micrantha, commonly known as coastal golden leaf, is a member of the family Phyllanthaceae. In preliminary studies nine fractions, named F1 - F9, were obtained by fractionating the crude methanol extract of the stem bark of Bridelia micrantha using column chromatographic techniques. The fraction F6 was the most active when tested for antibacterial activity. Thus, toxicity of this fraction was investigated for further use. The present study evaluated the acute and sub-chronic toxicity of the crude methanolic bark extract of Bridelia micrantha and its fraction. The acute toxicity was carried out according to the experimental protocol of Organization for Economic Co-operation and Development (OECD). The plant extract or the fraction F<sub>6</sub> was administered orally to female mice at a single dose of 2000 mg/kg and the animals were observed for any behavioral changes or mortality for 14 days. In the sub-chronic toxicity study, the extract and fraction were administered orally at 200, 400 and 800 mg/kg bw/day for 28 days to healthy Wistar rats. The general behavior and body weight of the rats were recorded daily. At the end of the experimental period, hematological and biochemical analyses, changes in vital organ weight (liver, lung, heart, spleen and kidney), and histopathological examination of the liver and kidney were performed. No mortality or adverse effects were noted at the 2000 mg/kg dose during the oral acute toxicity test. In the sub-chronic study, the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> induced no mortality or treatment-related adverse effects on body weight, general behavior, relative organ weights, hematological and biochemical parameters. Histopathological examination of the liver and kidney showed normal architecture suggesting no morphological alterations. In conclusion, the oral administration of the crude methanolic bark extract of Bridelia micrantha and the fraction F<sub>6</sub> for 28 days at a dosage of up to 800 mg/kg did not induce t
基金Supported by the National Natural Science Foundation of China(No.81171542 and No.81471995)
文摘Objective： To evaluate the acute and sub-chronic toxicity of intravenously administered tetrandrine（TET） in female BALB/c mice. Methods： The median lethal dose（LD_（50）） of intravenously administered TET was calculated in mice using Dixon＇s up-and-down method. In the acute toxicity study, mice were intravenously administered with TET at a single dose of 20, 100, 180, 260 and 340 mg/kg, respectively and were evaluated at 14 days after administration. In the sub-acute toxicity study, mice were intravenously administered various doses of TET（30, 90 and 150 mg/kg） each day for 14 consecutive days. Clinical symptoms, mortality, body weight, serum biochemistry, organ weight and histopathology were examined at the end of the experiment, as well as after a 1-week recovery period. Result： LD_（50） was found to be 444.67±35.76 mg/kg. In the acute toxicity study, no statistically significant differences in body weight, blood biochemistry, or organ histology were observed between the administration and control groups when mice were intravenously administered with single dose at 20, 100, 180, 260 and 340 mg/kg of TET（P〉0.05）. In the sub-acute toxicity study, no significant changes in body weight, biochemistry and organ histology were observed with up to 90 mg/kg of TET compared with the control group（P〉0.05）, however, in the 150 mg/kg administered group, TET induced transient toxicity to liver, lungs and kidneys, but withdrawal of TET can lead to reversal of the pathological conditions. Conclusions： The overall findings of this study indicate that TET is relatively non-toxic from a single dose of 20, 100, 180, 260 or 340 mg/kg, and that up to 90 mg/kg daily for 14 consecutive days can be considered a safe application dose.
基金Department of Science and Technology of Hubei Province:Preclinical Study on Qingfei Dayuan granules (No.2021BGE017)
文摘OBJECTIVE:To study the anti-inflammatory and anti-tussive effects of Qingfei Dayuan granules(清肺达原颗粒,QFDY),and to evaluate the acute and sub-chronic toxicity of QFDY.METHODS:Anti-inflammatory effects were evaluated by murine model of xylene induced ear edema in mice.Ear swelling degree was calculated and tumor necrosis factor-α,interleukin-1βand interleukin-6 were determined.Anti-tussive evaluations were carried out in the mouse cough model induced by ammonia liquor.Latent period cough and number of cough within 3 min were counted.In acute toxicity study,the rats were randomly divided into test group and solvent control group.Body weighs,food intakes and general clinical signs were monitored.In the sub-chronic toxicity study,QFDY was administered to rats at 0,4,8 and 16 g/kg per day for 28 and 30 d of post treatment was conducted.Mortalities,clinical signs,body weight changes,food intakes,ophthalmological examinations,hematological parameters,biochemical indicators,electrolyte indicators,urinalyses and histopathological examinations were monitored.RESULTS:QFDY significantly inhibited the development of ear edema in anti-inflammatory assay and decreased cough frequency caused by ammonia liquor.The results presented a dose-effect relationship.In acute toxicity study,no abnormality exhibited at dose of 24.0 g/kg per day during the 14-d observation period.In the sub-chronic toxicity study,higher reticulocyte count,lymphocyte and lower Cl-,blood urea nitrogen were analyzed compared with the solvent control group.But the differences were considered to be incidental and not clinically toxic.Obvious dose-effect relationship of urine color was observed,and the three test groups at the end of the experiments resulted in significant increase in urobilinogen,bilirubin,ketone body and urine leukocyte.However,all the positive indicators returned to normal in the recovery period.Therefore,no toxicological changes were found during the study period.CONCLUSION:QFDY showed significant anti-inflammatory and anti-tussiv
文摘Background:Phyto-medicine represents a vast pool of novel drug development,but understanding their safety requires elaborate,multifaceted approaches,including toxicity studies.Objective:This study investigated the effects of 90 days of oral administration of Datura stramonium(DSE)leaf extract in Rats.Methods:In the oral acute toxicity study,mice were treated with a single oral gavage of DSE at 500,1000,and 2000 mg·kg^(-1)/d,po and observed for signs of acute toxicity for 14 days.In the sub-chronic study,rats were randomized into four Groups(A-D).Group A received distilled water(10 mL·kg^(-1),po)while groups B-D received DSE(10,50 and 250 mg·kg^(-1)/d,po,respectively)orally for 90 days uninterrupted.Animals were weighed weekly,with food and water measured daily and relevant parameters assayed at the end of the 90days administration.Results:In acute toxicity studies,oral administration of up to 2 g·kg^(-1)/d,po of DSE did not elicit any semblance of toxicity or mortality within 24 h to 14 days.In the 90days studies,DSE(250 mg·kg^(-1)/d,po)decreased the body weight,brain weight,and food intake in female rats.DSE(10-250 mg·kg^(-1)/d,po)increased the red blood cell(RBC),packed cell volume(PCV)and hemoglobin(Hb)in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the triglycerides(TG),cholesterol and low-density lipoprotein(LDL);and decreased HDL in both sexes.DSE(10-250 mg·kg^(-1)/d,po)increased the white blood cells(WBC)and platelets in female rats.DSE(10-250 mg·kg^(-1)/d,po)decreased the alkaline phosphatase(ALP)and alanine transaminase(ALT)in both studies.Serum urea level was decreased in both sexes.DSE(250 mg·kg^(-1)/d,po)decreased male rats’serum sodium ion levels.Liver,brain,testes and kidney showed severe lesions at 250 mg·kg^(-1)/d,po of the extract.Conclusion:D.stramonium is safe on acute exposure and relatively safe on sub-chronic oral administration.How-ever,prolonged use,especially at high doses,could cause Liver,brain and kidney toxicities;and abnormal lipid metabolism.
基金supported by the Scientific Research Project on Marine Public Welfare Industry [No.201505021] of National Oceanic Administration’s in China
文摘Objective To explore the possible long‐term health effects of the defoamer used in seawater desalination by sub‐chronic toxicity testing. Methods Blood analysis, internal organ assessment, and histopathological examination were carried out in rats exposed to low, medium, and high(0.5, 1.0, and 2.0 g/kg BW, respectively) doses of defoamer for 90 days through oral administration. Results The high dose group showed decreased blood alanine aminotransferase and aspartate aminotransferase(P < 0.05). All doses resulted in a significant increase in albumin and decrease in globulin(P < 0.05). The direct bilirubin and indirect bilirubin were decreased in the medium and high dose groups(P < 0.05). All dose groups showed significant induction of alkaline phosphatase(P < 0.05). Pathological examination revealed a case of liver mononuclear cell infiltration in the medium dose group and three cases of liver congestion, steatosis of hepatic cells around the central vein, and punctate necrosis with multiple focal mononuclear cell infiltration in male rats administered the high dose. The No Observed Adverse Effect Level was 0.5 g/kg BW in rats, with albumin and total bilirubin as health effect indices. Conclusion Long‐term defoamer exposure may cause liver injury but has no significant impact on renal function in rats. The effect on blood cells in female rats was more prominent than that in male rats.
基金This work was supported by US India Fund for Cultural and Scientific Cooperation under project No.N-904-660.
文摘Objective To investigate the effect of Lead (Pb) acetate exposure on Semliki forest virus (SFV) pathogenesis in mice. Methods Different doses (62.5, 125, 250 and 500 mg/Kg body weight) of Pb dissolved in normal saline were given to mice by oral intubation in a sub-acute (28 days) and sub-chronic (90 days) regimen followed by SFV infection. Morbidity, mortality, clinical symptoms, mean survival time (MST), changes in body and organ weight, accumulation of lead in soft tissues, virus titre in brain and histopathological alterations were compared between lead exposed and infected groups. Results Early appearance of virus symptoms, increased mortality, decreased MST, enhanced SFV titre and greater tissue damage were observed in lead exposed-SFV-infected mice. Conclusion Pre-exposure to lead increases the susceptibility of mice towards SFV infection. Further studies are suggested in view of the persistence of lead in the environment and the possibility of infection by microbial pathogens.
文摘In current study toxicological profile of a commonly used herbal formulation was evaluated that is used extensively for gynecological disorders like menorrhagia, metrorrhagia, leucorrhea, irregular menstrual cycle, pre-menstrual syndrome and post-menopausal bleeding. It was also claimed to strengthen endometrium and ovaries. Since this herbal formulation was been used by a large number of population hence there was a need to assess acute and sub-chronic toxicity. Acute oral toxicity (LD50) was observed in albino mice using standard protocols whereas sub-chronic, hematological and histopathological studies were assessed on 24 albino rabbits after giving herbal formulation for 60 days in two doses (20 and 60 mg/kg) against control groups. The outcomes of present study showed that the drug is safe up to 5000 mg/kg following acute oral toxicity test and no mortality was observed during sub chronic toxicity studies. Results of sub-chronic toxicity did not show any significant changes in biochemical, hematological and histopathological parameters. However, some indicators such as urea, creatinine, hemoglobin, and RBC count were altered, but these changes do not correlate with the histopathological results and may be associated to intra individual variations. Despite the safety of the drug in few animals, clinical trials and more investigations on a large number of animals are essentially needed to establish safety and efficacy of the herbal formulation.
基金Supported by the Incubation Program for Science and Technology Innovative Research Team in Sichuan Province of China(2011-JTD0035)Program of Department of Education in Sichuan Province of China(10ZB050)the Program of Department of Education in Sichuan Province of China(11ZZ022)
文摘[ Objective] Effects of sub-chronic intoxication of 1,8-cineole on body weights, routine blood indexes and biochemical indexes of mice were investigated. [Method] One hundred and sixty mice with body weights of 15 -17 g were randomly divided into four groups （forty mice per group）. Mice were injected to 1, 8 - cineole with doses of 192.45,64. 15 and 21.38 mg/kg body weight （ test groups） and the water solution of tween-80 with a volume fraction of 0.5% （ control group） respectively. Each mouse was administered orally at the dose of 0.2 mL per 10 g body weight once a day consecutively for 90 d. The body weight, routine blood indexes and serum biochemical indexes of mice were determined on the 30^th d, 60^th d, 90^th d and the 30^th d after stopping the administration of 1,8-cineole. [ Result] The effects of 1, 8-cineole on the body weight, routine blood indexes and serum biochemical indexes of mice with the doses of 64.15 and 21.38 mg/kg body weight had no statistically significant difference compared with the control group （P 〉0.05 ）. 1, 8-cineole with the dose of 192.45 mg/kg body weight exhibited different influences on routine blood indexes and serum biochemical indexes of mice after the oral administration of 1,8-cineole for 60 d and 90 d, and statistically significant differences in many blood biochemical indexes were observed （P 〈 0.05 ）. However, the differences in routine blood indexes and serum biochemical indexes were not statistically significant between the test groups and the control group at the 30＇h d after stopping the administration of 1, 8-cineole （ P 〉 0.05）. [Condusion] 1,8-cineole had sub-chronic oral toxicity to mice. The no observed adverse effect level （NOAEL） of 1,8-cineolc was 64.15 mg/kg body weight and the lowest observed adverse effect level （LOAEL） of 1,8-cineole was 192.45 mg/kg body weight. Effects of 1, 8-cineole on blood biochemical indexes of mice were in short term and reversible.
文摘Dibutyltin dilaurate functions as a stabilizer for polyvinyl chloride. In this study, experimental rats were intragastrically administered 5, 10, or 20 mg/kg dibutyltin dilaurate to model sub-chronic poisoning. After exposure, our results showed the activities of superoxide dismutase and glutathione peroxidase decreased in rat brain tissue, while the malondialdehyde and nitric oxide content, as well as nitric oxide synthase activity in rat brain tissue increased. The cell cycle in the right parietal cortex was disordered and the rate of apoptosis increased. DNA damage was aggravated in the cerebral cortex, and the ultrastructure of the right parietal cortex tissues was altered. The above changes became more apparent with exposure to increasing doses of dibutyltin dilaurate. Our experimental findings confirmed the neurotoxicity of dibutyltin dilaurate in rat brain tissues, and demonstrated that the poisoning was dose-dependent.
基金Supported by the Postgraduate Innovative Scientific Research Foundation Program of Helongjiang Province (YJSCX2012-026HLJ)
文摘A total of 40 Wistar rats, weighing 130-140 g, were allocated randomly into four groups. They were orally administrated with 0 （control group, GC）, 64.18 （low-dose group, GL）, 128.36 （middle-dose group, GM）, and 256.72 （high-dose group, GH） mg aluminum chloride （AlCl3） per kilogram body weight in drinking water for 120 days. Kidney coefficient and aluminum （Al） concentrations in blood and kidney were determined, and renal autopsy and histological changes were observed. The results showed that kidney coefficient in all Al-treated groups were obviously lower than that in GC （P〈0.01） and there was a dose-effect relationship. The kidneys were solid, lusterless and pale brown with white necrosis point on surface. Under electron microscope, renal cortex became thin, the renal tubule was narrowed and the epithelium dissolved; the renal glomerulus became atrophied and the glomerular became vasodilator. The Al concentrations in blood and kidney were higher in all Al-treated rats than those in GC （P〈0.01）, and there was a dose-effect relationship. The results indicated that sub-chronic Al exposure could lead to Al accumulation in kidney, restrain the development of kidney and cause the pathologic damage in rats.
基金supported by the National Key R&D Program of China[2019YFC1605203]China Food Safety Talent Competency Development Initiative:CFSA 523 Program
文摘Objective The present study was undertaken to evaluate the subchronic oral toxicity of sodium dehydroacetate(DHA-Na)and to determine the point of departure(POD),which is a critical factor in the establishment of an acceptable dietary intake.Methods DHA-Na was administered once daily by gavage to Sprague–Dawley rats at dose levels of 0.0,31.0,62.0,and 124.0 mg/kg BW per day for 90 days,followed by a recovery period of 4 weeks in the control and 124.0 mg/kg BW per day groups.The outcome parameters were mortality,clinical observations,body weights,food consumption,hematology and clinical biochemistry,endocrine hormone levels,and ophthalmic,urinary,and histopathologic indicators.The benchmark dose(BMD)approach was applied to estimate the POD.Results Significant decreases were found in the 62.0 and 124.0 mg/kg BW groups in terms of the body weight and food utilization rate,whereas a significant increase was found in the thyroid stimulating hormone levels of the 124.0 mg/kg BW group.Importantly,the 95%lower confidence limit on the BMD of 51.7 mg/kg BW was modeled for a reduction in body weight.Conclusion The repeated-dose study indicated the slight systemic toxicity of DHA-Na at certain levels(62.0 and 124.0 mg/kg BW)after a 90-day oral exposure.
基金The authors are grateful to Yunnan Major Science and Technology Project(2019ZF003,2019FY003004)the National Key Research and Development Program of China(2017YFC1704007)the general program of applied basic research of Yunnan province(2019FB116)for partial financial support.
文摘Alstonia scholaris(L.)R.Br.,an evergreen tropical plant rich in indole alkaloids with significant physiological activity,is traditionally used to treat respiratory diseases in China.This study was conducted to establish the toxicity profile of the alkaloid extract(TA)of A.scholaris leaves in non-rodents.After oral administration of a single dose(4 g/kg.bw),a num-ber of transient symptoms,such as unsteady gait,drooling,emesis,and reddening of peri-oral mucosa,were observed,but no treatment-related mortality.A sub-chronic toxicity study with a range of doses of TA(20,60 and 120 mg/kg.bw)was conducted for a 13-week treatment period,followed by 4-week recovery observation.Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group,no clinical changes were observed in TA-treated animals.Data from electrocardiography,bone marrow,urine,fecal,hematology and clinical chemistry analyses were comparable between TA-treated and control animals.No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups.Accordingly,the non-observed-adverse-effect-level(NOAEL)of TA was established as 120 mg/kg.bw.Our results add further knowledge to the safety database for indole alkaloid extracts from A.scholaris with potential utility as novel drug candidates.
