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Objective:To observe the possible toxicity of long-term intravenous injection of Tanreqing injection in Beagle dogs， so as to provide experimental data for its clinical safe medication. Method:A total of 32 Beagle dogs （16 males and 16 females） were randomly divided into the low- （2.5 mL·kg<sup>-1</sup>）， medium- （5.0 mL·kg<sup>-1</sup>）， and high-dose （10.0 mL·kg<sup>-1</sup>） Tanreqing injection groups and control group according to their body mass indices， with eight dogs in each group. In the waking state， the dogs were treated with intravenous injection of corresponding drugs into the medial cephalic vein of forelimb for 13 weeks， followed by four-week drug withdrawal. After the observation of general condition， body mass， and food consumption， the Beagle dogs were subjected to electrocardiography， ophthalmoscopy， hematological examination， serum biochemistry， and blood coagulation test in the middle of medication （week 6）， at the end of medication （week 13）， and during recovery （week 17）. Then the gross anatomy was conducted for calculating the major organ coefficients and observing the histopathological changes. Result:No obvious toxic reaction was found in each group， but the decreased fibrinogen and increased Kupffer's cells phagocytizing yellow-brown pigment in hepatic sinusoids were observed in the high-dose Tanreqing injection group following three months of medication. Reduction of fibrinogen was not observed in recovery period， but Kupffer's cells that phagocytized yellow-brown pigment still existed. Conclusion:The intravenous injection of Tanreqing injection at 2.50 mL·kg<sup>-1 </sup>（low dose）， 5.00 mL·kg<sup>-1</sup> （medium dose） or 10.00 mL·kg<sup>-1 </sup>（high dose） for three months in Beagle dogs resulted in no obvious toxic reaction. However， it is still suggested to test the liver function and blood coagulation after long-term administration of high-dose Tanreqing injection.
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Objective: To observe the long-term toxicity of chelerythrine on the morphology of lung tissue and the expression level of nuclear factor-kappa B (NF-κB) in lung tissue of the rats, and to investigate the related mechanism which causing the lung tissue damage of rats. Methods: A total of 120 Wistar rats were divided into control group (given normal saline) and low (3. 7 mg middot; kg-1), moderate (5. 6 mg middot; kg-1), high (8. 4 mg middot; kg-1) dosages of chelerythrine groups (n=30). The general condition of rats in various groups was observed; HE staining was used to observe the morphology of lung tissue of the rats in various groups; the serum interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) levels of the rats in various groups were measured by ELISA method; real-time fluorescence quantitative PCR and Western blotting methods were used to detect the mRNA and protein levels of NF-κB and intercellular adhesion molecule-1 (ICAM-1). Results: The accumulative mortality of the rats in high dosage of chelerythrine group was the highest, followed by moderate and low dosages of chelerythrine groups. The body weights and food intakes of the rats in different dosages of chelerythrine groups were significantly lower than that in control group (P<0. 05), while the body weight and food intake of the rats in high dosage of chelerythrine group were lower than those in low and moderate dosages of chelerythrine groups (P<0. 05). Chelerythrine led to pulmonary congestion and bloody ascites of the rats. The HE staining results showed that the injuries of lung tissue in different dosages of chelerythrine groups were aggravated with the increasing of the dosage of chelerythrine. Compared with control group, the levels of IL-6, IL-8, and TNF-α in serum of the rats in different dosages of chelerythrine groups were increased significantly (P< 0.05); compared with low and moderate dosages of chelerythrine groups, the levels of IL-6, IL-8, and TNF-α in serum of the rats in high dosage of chelerythrine group were increased significantly (P<0. 05). Compared with control group, the expression levels of NF-κB and ICAM-1 mRNA and proteins in lung tissue of the the rats in different dosages of chelerythrine groups were increased significantly (P<0. 05) in a dose-dependent manner; compared with low and moderate dosages of chelerythrine groups, the expression levels of NF-κB and ICAM-1 mRNA and proteins in lung tissue of the rats in high dosage of chelerythrine group were increased (P<0. 05). Conclusion: Chelerythrine has a long-term toxic effect on lung tissue in a dose-dependent manner of the rats. Moderate and high dosages of chelerythrine may aggravate the toxic lung injury through activation of NF-κB and production of inflammatory cytokines.
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Objective: To screen the extraction process of Wuzi Yanzong plus and minus Recipe (WYR) by pharmacodynamics and long-term toxicity test, and optimize it by orthogonal experiment to determine the best extraction process of WYR. Methods Long-term toxicity experiments were carried out on different processed WYR samples. The penile erection latency and sex hormone levels in rats with kidney-yang deficiency were used as pharmacodynamic indicators. The results of long-term toxicity and efficacy experiments were combined to screen out the optimal process plan. Using the content of ingredients and the rate of ointment as indicators, the orthogonal test was used to screen the optimal level of different extraction processes and verified. Results Long-term toxicity test results showed that all mice survived healthily and no obvious toxicity was observed. The results of pharmacodynamic experiments showed that the extracts of Morindae Officinalis Radix, Eucommiae Cortex, Taxilli Herba, Dipsaci Radix, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle were refluxed with 70% ethanol, and the remaining medicinal materials were extracted with 70% ethanol as the solvent to obtain the best extraction method of WYR. The suitable extraction process was as follows: Morindae Officinalis Radix, Eucommiae Cortex, Taxilli Herba, Dipsaci Radix, and Glycyrrhizae Radix et Rhizoma Praeparata cum Melle were extracted three times with 10 times 70% ethanol for 2.0 h each time; The remaining medicinal materials were percolated with 10 times 70% ethanol at 1.5 mL/min. The medicinal herbs were firstly soaked for 16 h before percolation. Conclusion WYR can significantly improve the penile erection latency and sex hormone levels in rats with kidney yang deficiency. The optimal process conditions are reasonable and feasible, which provides a basis for the follow-up development of WYR.
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Objective:To observe effect of long-term administration of rhein on the kidney toxicity of mice, and explore its possible toxic mechanism, in order to provide some basis for rational clinical drug use and further research. Method:The 30 Kunming mice (half male and half female) were randomly divided into 3 groups:control group, low-dose rhein group and high-dose rhein group (0.175,0.35 g·kg-1), with 10 mice in each group. The intragastric administration lasted for 60 days. During administration, general situations of the mice were observed and recorded. Serum urea nitrogen (BUN), creatinine (SCr), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected after drug withdrawal. Kidney index was calculated, and glutathione peroxidase (GSH-Px) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio were measured. The kidneys were collected and histopathologically examined, and the protein expressions of transforming growth factor beta (TGF-β1) and cysteine aspartic acid specific protease-3 (Caspase-3) were detected by immunohistochemistry. Result:Compared with the control group of the same sex, BUN and SCr of the administration group increased significantly(PPPPα and Caspase-3 increased significantly(PPPPβ1 was increased(PConclusion:The toxicity of rhein in the kidney of mice was obvious at the dose of 0.35 g·kg-1·d-1, and the toxicity in male organism is more obvious. The mechanism of its potential toxicity may cause the imbalance of glutathione antioxidant system, induce excessive oxidation, trigger inflammatory reaction, activate the expression of Caspase-3, and then induce apoptosis.
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Objective:To observe the effect of long-term administration of emodin on the kidney toxicity of mice, explore its possible toxic mechanism, and provide some basis for clinical rational drug use and further research. Method:The 30 Kunming mice, half male and half female, were randomly divided into 3 groups:control group, emodin low dose group and emodin high dose groups (0.8, 1.6 g·kg-1), 10 mice in each group. Continuous intragastric administration was given for 11 weeks. During administration, the general situation of the mice was observed and recorded. After treatment, the serum urea nitrogen (BUN), creatinine (SCr), malondialdehyde (MDA), superoxide dismutase (SOD) tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) were detected. Kidney index was calculated and glutathione peroxidase (GSH-Px) and reduced glutathione/oxidized glutathione (GSH/GSSG) ratio were measured. The kidneys were taken for histopathological examination and the protein expression levels of transforming growth factor-β1(TGF-β1) and cysteine aspartic acid specific protease-3 (Caspase-3) were then detected by immunohistochemistry assay. Result:As compared with control group of the same sex, the weight of mice in the administration groups was decreased significantly, renal index was decreased while BUN and SCr levels were increased significantly (PPPPα was increased significantly (PP PPConclusion:The long-term administration of emodin at a large dose would show toxicity effect on mice kidney, and the toxicity was obvious at the dose of 1.6 g·kg-1·d-1, but there was no significant difference between the sexes. The mechanism of its potential toxicity may be related to the disorder of oxidation system, the injury of oxidative stress, the triggering of inflammatory reaction, and the apoptosis of cells.
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OBJECTIVE： To investigate the acute toxicity， long-term toxicity， skin irritation and anaphylaxis of Bee venom （BV） plastics， and to evaluate its preclinical safety. METHODS： The acute toxicity of BV plastics to rats was investigated after administration of high-dose， medium-dose and low-dose （144， 96， 48 mg/kg） of BV plastics. The long-term toxicity of BV plastics was investigated by continuous administration of high-dose， medium-dose and low-dose （72， 48， 24 mg/kg） of BV plastics for 28 days. The irritation of intact and damaged skin in rabbits with 8 mg/kg BV plastics was investigated by using the self-control method of left and right homologous body. The skin anaphylaxis of guinea pig were investigated after sensitized with 15 mg/kg BV plastics on the left back （on 0， 7th， 14th day） and stimulated with 15 mg/kg BV plastics on the right back. RESULTS： During the acute toxicity experiment with BV plastic，the weight of rats and the changes of viscera were normal，and there was no relevant toxic reaction. Long-term toxicity test results showed that no significant pathological changes were observed at 24 h after the last administration； the spleen index of rats in BV low-dose group， testicular index in middle-dose group and epididymis index in high-dose and middle-dose groups were significantly increased， while PT in plasma of rats in BV medium-dose and low-dose groups was significantly prolonged （P＜0.05）. There were no abnormal changes in organ appearance， other organ index， coagulation index and blood biochemical index. All above indexes became normal at the end of 2-week recovery period. Skin irritation test showed that BV plastics could cause slight erythema and obvious scab on the skin of rabbits which along with little irritation on intact or damaged skin. Skin anaphylaxis test showed that BV plastics produced mild erythema in the skin of guinea pigs， belonging to light allergy. CONCLUSIONS： No acute or long-term toxicity is observed after transdermal administration of BV plastics， which is safe and only causes mild irritation and irritability to skin， indicating there is good safety of the plastic under experiment doses.
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OBJECTIVE： To study the long-term toxicity of Liqi sanjie extractum in rats after intragastric administration， and to provide reference for safety evaluation before clinical practice. METHODS： A total of 160 rats were randomly divided into control group （normal saline） and Liqi sanjie extractum low-dose， medium-dose and high-dose groups （7.828 0， 15.656 0， 31.312 0 g/kg， calculated by crude drug）， with 40 rats in each group. They were given relevant medicine intragastrically once a day from Monday to Saturday. The experimental period was 120 days， and the recovery period was 30 days after the end of the experiment. General information of rats was observed， and body weight and feed consumption of rats were measured once a week. At the 61st day of administration， the end of administration and the end of recovery period， 10， 20 and 10 rats were collected from each group to observe their hematology， blood biochemistry， organ coefficient and histopathology changes. RESULTS： From 61st day to 120th day of administration， the rats of Liqi sanjie extractum high-dose group had hair loss and erection， and recovered after withdrawal of medicine. During medication， the body weight of mice in Liqi sanjie extractum low-dose and medium-dose groups increased faster than control group， while the body weight of rats in Liqi sanjie extractum high-dose group increased slower than control group. Compared with control group， the feed consumption of Liqi sanjie extractum low-dose group increased， while those of Liqi sanjie extractum medium-dose and high-dose groups decreased； the rats were recovered after drug withdrawal. On the 61st day of administration and after the end of administration， some hematological indexes， blood biochemical indexes and organ coefficients of rats in administration group were significantly different from those of control group （P＜0.05 or P＜0.01）. The hematology， blood biochemistry and organ coefficients of rats were basically recovered after the end of the recovery period. The number of erythrocyte， hematocrit， standard deviation of erythrocyte width， albumin， globulin ratio and potassium K+ levels in Liqi sanjie extractum low-dose group were significantly lower than those in control group （P＜0.05 or P＜0.01）. The absolute value of intermediate cells in blood of rats in Liqi sanjie extractum medium-dose group was significantly higher than that of control group （P＜0.05）， and the mean hemoglobin concentration， K+ and uterine coefficient in blood were significantly lower than those of control group （P＜0.05）. The number of white blood cells， absolute value of lymphocyte， absolute value of intermediate cells， the percentage of intermediate cells， prothrombin time and spleen coefficient in Liqi sanjie extractum high-dose group were significantly higher than those in the control group （P＜0.05 or P＜0.01）. Mean hemoglobin concentration， granulocyte percentage， albumin， alkaline phosphatase and K+ were significantly lower than those in the control group （P＜0.05 or P＜0.01）. No abnormalities in systemic autopsy and histopathology were noticed in rats. CONCLUSIONS： Long-term intragastric administration of Liqi sanjie extractum can cause certain toxic reactions in rats， and low dose of Liqi sanjie extractum causes less and lighter toxic reactions which can be automatically recovered after drug withdrawal. It can provide reference for the determination of clinical safe dose.
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Objective To investigate the long-term toxicity of anti-inflammatory and anticoagulant tick anticoagulant peptide (TAP)-staphylococcal superantigen like protein-5 (SSL5) fusion protein in normal rats.MethodsSD rats were intraperitoneally injected with TAP-SSL5 (1mg/kg, every other day) for eight weeks and followed up for one week.The general behavior, weight, blood routine test, blood biochemistry and organ indexe were measured.ResultsOur results showed that there were no significantly difference between the TAP-SSL5 treated rats and the control on general behavior, weight, blood routine test, blood biochemistry, organ indexe and pathology.ConclusionThe fusion protein TAP-SSL5 with little long-term toxicity for rats is proved to be a safe drug.
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OBJECTIVE:To investigate toxic reaction of Compound zedoary turmeric oil cream in experimental rats with long-term consecutive transdermal administration,and to provide reference for safe use of it in the clinic. METHODS:60 SD rats were randomly divided into blank control (cream matrix) group,Compound zedoary turmeric oil cream intact skin and damaged skin low-dose and high-dose(5%,10%)groups,with 12 rats in each group,half male and half female. All of them were given relevant medicine twice a day. 92 d consecutive medication later,general situation of rats were observed,and body weight,blood routine(WBC,RBC,HGB,LYMPH,etc.)and blood biochemical indicators(AST,ALT,PA,etc.)were all detected;systemati-cal observation of organs,organ coefficient calculation and histopathology examination were carried out. RESULTS:There was no statistical significance in those indicators between Compound zedoary turmeric oil cream groups and blank control group (P>0.05),except hemoglobin decreased in intact skin low-dose group,while hemoglobin decreased,LYMPH and PA increased in dam-aged skin high-dose group(P<0.05). Pathology results showed that Compound zedoary turmeric oil cream had no significant toxici-ty for the main organs. CONCLUSIONS:Compound zedoary turmeric oil cream has no long-term toxicity to experimental rats.
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OBJECTIVE To clarify the long-term toxicity to the respiratory system in a rat model of acute lung injury (ALI) induced by a single low-dose of perfluoroisobutylene(PFIB) inhalation expo?sure,and observe the possible beneficial effect of early intervention via Qingkailing(QKL) injection. METHODS Totally 224 male Wistar rats were randomly divided into 4 groups:normal control group in which air exposure was followed by a saline 10 mL · kg-1(ip),QKL control group in which QKL 10 mL · kg-1 was ip given after air exposure,PFIB exposure group in which rats were exposed to PFIB 280 mg·m-3 for 5 min only,and QKL treatment group in which QKL 10 mL·kg-1 was given ip at 1 h after PFIB exposure. Lung functions of rats were measured at 24 h,3,6,12,24,36 and 48 weeks after exposure. The arterial blood gas,lung coefficient,protein content in bronchoalveolar lavage fluid(BALF),hydroxy?proline(HYP) content in lung tissue and plasma,and other indicators were detected or analyzed. RESULTS Within 24 h after PFIB exposure,the lung coefficient and protein content in BALF were increased significantly(P<0.01),whereas the PaO2(P<0.01) and SaO2(P<0.05) indices in arterial blood decreased significantly in PFIB group compared with normal control. The inhalation time , exhalation time,tidal volume(TV),expired volume(EV)and relaxed time were reduced significantly (P<0.01). However,all the above indicators returned to normal in 3 weeks,but TV,EV and peak expiratory flow were significantly lower than in normal group at 48 weeks(P<0.05). HYP contents in lung tissues,compared with normal control(P<0.05),were reduced significantly within 24 h after PFIB exposure,increased significantly in 6 weeks(P<0.05),then returned to normal in 12 weeks. HYP contents in plasma increased significantly compared with normal control(P<0.05) within 24 h after PFIB exposure but returned to normal in 3 weeks. The protein contents in BALF of QKL treatment group were significantly lower than those in PFIB group(P<0.01) within 24 h after PFIB exposure. From 24 h to 24 weeks after PFIB exposure,changes of pulmonary functions were similar to those in PFIB group. At 48 weeks,TV and EV in QKL treatment group were more significantly increased than those in PFIB group(P<0.05). CONCLUSION Rats with ALI induced by a single low dose of PFIB exposure undergo compensatory repair except for pulmonary capacity and pulmonary ventilation functions. Early treatment with QKL reduces protein content of BALF and alleviates pulmonary edema,and has some beneficial effect on lung function recovery later.
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Objective: To observe the property and degree of long-term toxicity of Kuntai and evaluate whether the toxic injure can be prevented or recovered, so as to provide the reference for clinical safe use. Methods: One handred and twenty rats were randomly divided into four groups, Kuntai (25.0, 12.5, and 5.0 g/kg) groups and control (ig same volume of distilled water) group for all being treated for 180 d, respectively. Then the rats were sacrificed 2/3 (n = 20) in each group and the anatomy and pathological biochemical detection were carried on. And the remainings (n = 10) were sacrificed after 30 d of withdrawal drug to use for the reversible experiment. Results: There is no significance of the extract from Kuntai Capsule on the growth/hematopoietic function/biochemical criterion of serum or the pathological feature, i. e. toxicity changes with obvious injury in heart, liver, spleen, lung, kidney, uterus, ovaries, testes, the pituitary gland, and brain. Conclusion: There is very low toxicity of the extract from Kuntai Capsule for the long-term safe use which is benefit in clinic.
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Objective To observe the toxicity of fangyouling after one month’s transdermal administration in rabbits and evaluate its security. Methods Forty rabbits were randomly divided into 4 groups including a control group and low,middle and high dose groups of fangyouling. The rabbits in the control group were administered with sunflower oil,and the other rabbits were administrated dermally with fangyouling of 50,300 and 2 000 mg/kg respectively once a day for 4 weeks. The general con?dition,the skin irritation reaction,body weight,food consumption,hematology,blood biochemistry,organ coefficients and his?topathological changes of all the rabbits were observed. Results There was no obvious effect on the general condition in all the rabbits. However,the mild skin irritation was observed in 2 rabbits of the middle dose group and 4 rabbits of the high?dose group. The decreases of body weight and food consumption were noted in the high dose group. No changes were detected of hema?tology,blood biochemistry or viscera pathological at all dose levels. Conclusion The dose of non?toxic response of fangyouling is 50 mg/kg at this study condition.
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Objective To observe the long-term toxicity of sustained-release dropping pills of Rhynchophylla total alkaloids in rats.Methods 80 Wistar rats were randomly divided into high dose group, middle dose group, low dose group and normal group. The rats were consecutively drenched for 12 weeks. The general status of the animals was observed daily in medication duration and body weight, daily appetite, quantity were recorded every 2 weeks. All animals were sacrificed on drenched 12 weeks and 2 weeks after discontinuation, then the content of WBC, RBC, Hb, PLT, LYM, NEU and ALT, AST, ALP, BUN, Cr were detected. Ratio of viscera was measured and the major organs were examined by the pathology.Results Continuous intragastric administration for 12 weeks after high dose group rats, poor diet, weight growth was slow;no significant changes of Hematology was found;The ALT, AST and ALP of high dose group rats increased[respectively(77.5±11.9)U/L,(210.4±21.7)U/L,(220.6±19.8)U/L], compared with the blank control group[respectively(55.2±12.1)U/L,(180.4±21.3)U/L,(190.3±22.6)U/L], the difference was statistically significant(P<0.05). The ratio of liver body in high dose group(3.86±0.29)was higher than the control group(3.52±0.25), the difference was statistically significant(P<0.05). And liver degeneration, focal necrosis was found.Conclusion The main chronic toxic damage is liver damage caused by sustained-release dropping pills of Rhynchophylla total alkaloids of long-term large delivery.
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Objective: To study the acute and long-term toxicity of brucea javanica oil subnanoemulsion injections ( BJOSI ) . Methods:The mice were given BJOSI by intravenous injection. The acute toxicity was observed and LD50 in mice was calculated by Bliss method. To observe the long-term toxicological effects, Beagle dogs were injected intravenously BJOSI once a day for 8-week du-ration with the dose of 20, 10 and 6 ml·kg-1 , respectively followed by 3-week recovery period. Results:LD50 of BJOSI in mice was 7. 388 g·kg-1 with 95% confidence limits of 6. 306-8. 656 g·kg-1 . The long term toxicity test showed that all the detected indices were within normal range in all groups, including general state, weight changes,hematological indices,biochemical indices,EEG,organ coefficients, morphological and histological changes, while there was an upward tendency of ALT and Cr in every BJOSI group without dose-effect correlation. The dogs could completely recover in three weeks after the administration. Conclusion:The results suggest that BJOSI has low toxicity,while the pathological changes are reversible, and attention should be paid to the function of liver and kidney.
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This study was aimed to observe the acute toxicity and long-term toxicity of Meng-Gen-Wu-Su-18 (MGWS-18) Pills, in order to provide references for safety application of this medicine in the clinical practice. MGWS-18 Pills suspension was intragastric administered to mice twice (0.2 mL/10 g) in 6 hours with maximal con-centration (0.4 g·mL-1). And the acute toxicity reaction was observed for 14 days. The dose of maximum, middle and minimum (3.67 g·kg-1, 1.84 g·kg-1, 0.92 g·kg-1) of MGWS-18 Pills were intragastric administered continuously to rats once a day for 180 days. The rats were observed 60 days after drug withdrawal. The results showed that the maximal tolerated dose (MTD) of MGWS-18 Pills was bigger than the dose of 16 g·kg-1 (which was equivalent to 436.36 times in clinical doses). There were significant differences on ALB, UREA, AST, TBIL, and CHOL between the control group and the maximum dose group of MGWS-18 Pills (P<0.05, or P<0.01) after 180 days of medica-tion. There were significant differences on ALB and UREA between the control group and the middle dose group (P< 0.05). There was no significant difference between the control group and the minimum dose group. Protein cast and degeneration necrosis at different levels of the epithelial cells of the proximal tubules were appeared in the maximum dose group after medication for 180 days. After 60 days of drug withdrawal, there were no significant dif-ferences on the general condition, body weight, hematological indexes, serum biochemical indexes, organ coefficient and etc. between the control group and each animal group. There was recovery tendency on the kidney damage of the maximum dose group. It was concluded that the basic safety intragastric administration dosage of MGWS-18 Pills in rats was 0.92 g·kg-1 (which was equivalent to 25 times in clinical doses).
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Balacaturbhadrika churna has an important place in pediatric practice in Ayurveda. Millennia of use of this formulation bears testimony to its safety when used for prolonged duration in children. This prompted us to initiate a long-term, acute oral toxicity evaluation of Balacaturbhadrika churna in rats. The study was carried out by administering Balacaturbhadrika churna orally once only in a dose up to 2000 mg/kg. For long–term toxicity, Balacaturbhadrika churna was administered in doses of 450 and 900 mg/kg orally for 45 consecutive days. The effects of the drug on ponderal changes, hematological, biochemical and histological parameters were noted. The acute toxicity experiment showed that the drug did not produce any signs and symptoms of toxicity (or mortality) up to the dose of 2000 mg/kg. Long–term toxicity results showed that, even at higher dose of 900 mg/kg, Balacaturbhadrika churna did not affect the parameters studied, to a significant extent. The doses employed for these toxicity studies were several times higher than normal clinical doses of Balacaturbhadrika churna, hence the observed changes will probably not become apparent at therapeutic dose level.
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The generation and activity of serum neuralizing antibody in cynomolgus monkeys and SD rats undergoing long-term toxicity study with antitumor peptides HM-3 were investigated.The rats were administered intravenously with HM-3 at doses of 4.5 mg/kg,13.5 mg/kg,and 40.5 mg/kg for 6 months,and the cynomolgus monkeys were administrated intravenously with HM-3 at doses of 3 mg/kg,9 mg/kg and 27 mg/kg for 6 months,respectively.Anti-HM-3 antibodies and their neutralizing activities in serum samples taken every month after the administrations were determined by ELISA and cell migration assay,respectively.During the long-term administrations,anti-HM-3 antibodies were generated in some SD rats at high and moderate dose groups,and the antibody-neutralizing activities could be detected in a number of these samples (P ＜0.05).However,activity could be detected in very few monkeys (P ＜ 0.05),and the antibody titers were not correlated with the neutralizing activities.Therefore,we conclude that the antigenicity of HM-3 was low,but after long-term administration at high dose,low affinity neutralizing antibody could be generated in small number of samples.
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OBJECTIVE:To investigate the long-term toxicity of repeated intramuscular injection of Escherichia coli O157∶H7 polysaccharide-conjugated vaccine(O157) in rats so as to provide safety evidence for clinical trials.METHODS:A total of 48 SD rats were randomly assigned to receive either 0.5 mL vaccine(containing 25 ?g polysaccharides) (immunization group,n=24) or phosphate buffered solution (PBS,control group,n=24) with the same volume for 3 times at a dose interval of two weeks.Sacrifice of 6 rats in each group were scheduled at 2 weeks after first immunization,and at 1,3,and 5 weeks after the third immunization,respectively for observation and determination of hematological and biochemical parameters,histopathology,specific antibody,myeloid tissue,the tissues in injection sites,etc.RESULTS:Compared with control group,immunization group showed no significant pathological change except the dynamic regular change of some hematological parameters induced by the immunization,and no immunologic system damage was observed.CONCLUSION:Repeated intramuscular injection with O157 vaccine in rats wouldn't cause overt toxicity and local irritation.
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OBJECTIVE:To study the long-term toxicity of Reketing granules.METHODS:The experiment was performed in 4 groups:one control group(normal saline)and three Reketing subgroups(188 g?kg-1,94 g?kg-1,18 g?kg-1).After intragastrical administration for 3 consecutive months,the blood routine,urine routine and serum biochemical indicators were measured in rats,and the autopsy of the major organs was performed.After drug withdrawal for 2 weeks,the above indexes were measured again to find out the abnormality.RESULTS:After 3-month medication,the rats experienced a gradual increase in body weight and developed well.In Reketing high dose-treated group,glutamate-pyruvate transaminase(GPT)and blood urea nitrogen(BUN)levels increased slightly;and except for lesion of liver and kidney in small number of rats,the peripheral hemogram,urine routine and the blood biochemical indicators were all normal.The above indexes and the pathological findings of the organs after drug withdrawal for 2 weeks were all normal.CONCLUSION:Reketing granules can lead to mild lesion of liver and kidney of rats during medication,but the symptoms disappear after drug withdrawal.
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OBJECTIVE:To evaluate the long-term toxicity of Ginkgolide B injection on Beagle dogs,and to provide safety evidences for clinical experiment.METHODS: A total of 24 Beagle dogs were equally assigned to receive placebo(control group,n=6) or Ginkgolide B injection at high,medium,and low doses(80,20,and 5 mg?kg-1) by iv gtt for 6 consecutive days per week for up to 90 days.There were 6 Beagle dogs(male: female =1∶1) in each group.All the laboratory indicators were monitored and the recovery of the Beagle dogs was observed.RESULTS: During medication,vomiting was noted in one dog in high dose group,and the clotting time in high and medium dose groups was prolonged obviously.During the recovery stage,one dog in high dose group was strong positive in urinary protein test.No significant drug-associated toxic reactions were noted judging from Beagle dogs' body weight,appetite,temperature,ECG,hematology,blood biochemical analysis,ophthalmology test,marrow test,urine routine test,histopathologic examination etc.CONCLUSION: The non-toxic dose of Ginkgolide B injection for Beagle dogs was 20 mg?kg-1.