ABSTRACT
<p><b>OBJECTIVE</b>To study the toxicokinetics and tissue distribution of total arsenic after giving different doses realgar to rats.</p><p><b>METHOD</b>The concentration of arsenic in blood, urine and main organs were determined after single oral administration of 3.738, 1.869, 0.935 g x kg(-1) realgar in rats.</p><p><b>RESULT</b>The distribution half life (t(1/2 alpha)) and elimination half life (t(1/2 beta)) of total arsenic were 7.73 h and 17.21 h respectively in high dose group. The apparent distribution volume (Vd) were 10.8, 5.6, 3.9 L x kg(-1) respectively, the total clearance (Cltot) were 0.437, 0.16, 0.111 L x h(-1) x kg(-1) respectively in the three groups. The excretion of total urine arsenic got rid of 5.5%-13.0% of realgar which given to rats in 96 hours. Arsenic could be detected distributing into rat's main organs and tissues after administration of a single dose. Suprarenal gland, bladder and ovary accumulated most of the arsenic, while liver, spleen, lung and kidney accumulated less. Heart, brain, stomach and testis accumulated the least amount.</p><p><b>CONCLUSION</b>It has nonlinear dynamics in the body of rats in toxic doses as the kinetics of realgar was changed according to the dosage.</p>
Subject(s)
Animals , Female , Male , Rats , Arsenicals , Pharmacokinetics , Drugs, Chinese Herbal , Pharmacokinetics , Toxicity , Random Allocation , Rats, Sprague-Dawley , Sulfides , Pharmacokinetics , Toxicity , Tissue DistributionABSTRACT
BACKGROUND: In order to improve the medication safety and remove export obstacles of Chinese preparations contained heavy metal and arsenide (cinnabar, realgar), it is necessary to carry on the evaluation on the efficacy and safety of cinnabar and realgar. At present, it has not been clear concerning to the pharmacodynamic mechanism of cinnabar and realgar in compound prescriptions yet.OBJECTIVE: To study the differences in cinnabar and realgar in angong niuhuang wan in the organism physiologically and pathologically so as to probe into those pharmacodynamic mechanism.DESIGN: A randomized and controlled trial.SETTING: Institute of Clinical Pharmacology of one university.MATERIALS: The experiment was performed in Institute of Clinical Pharmacology of Guangzhou University of Traditional Chinese Medicine in January 2003. Totally 51 male SD rats weighted varied from 250 g to 300 g were employed, provided by Experimental Animal Center of First Military Medical University of Chinese PLA.METHODS: SD rats were randomized into 6 groups(8-10 rats/group),named as normal group, normal & angong niuhuang san (integral recipe) group(278 mg/kg), normal & cinnabar and realgar omitted angong niuhuang san(disassembled recipe) group(222.7 mg/kg), cerebral edema model group(ligature on unilateral carotid artery by injection of pertussis bacilli (PB), 2 500 million/kg), model & integral recipe group (medication 278 mg/kg was done 1 hour before model preparation), model & disassembled recipe group(medication 222.7 mg/kg was done 1 hour before model preparation) . Five hours later after once medication(4 hours later after PB injection in model group), blood was collected and brain homogenate was prepared.MAIN OUTCOME MEASURES: Brain tissues, serum lactate dehydrogenase(LDH) activity and percentage enzyme activity of lactate dehydrogenase isoenzymes (LDH1-5).RESULTS: Compared with normal group, the general activity of LDH in normal & integral recipe group and normal & disassembled recipe group was significantly improved by 32.4% to 38.4% ( P ＜ 0.05); percentage enzyme activity of LDH1,2 was significantly increased( P ＜ 0.01 ), and that of LDH4, 5 was reduced( P ＜0.01) . Except LDH5, there were no significant differences in enzyme activity of isoenzymes in two groups. Compared with model group, the general activity of LDH in model & integral recipe group and model & disassembled recipe group was significantly improved by 23.4% to 38.5% ( P ＜ 0.01); percentage enzyme activity of LDH5 was significantly increased( P ＜ 0.01 ), there were no significant differences in two groups. In model & integral recipe group, percentage enzyme activity of LDH2,3 was significantly decreased( P ＜ 0.01), and that of LDH1,4 was no significant change. In model & disassemble recipe group, percentage enzyme activity of LDH1,4 was significantly reduced( P ＜ 0. 05, 0.01 ) and that of LDH2,3 was no significant change.CONCLUSION: In normal physiological state, angong niuhuang san produces a certain injuries on cardiac muscle and kidney. In pathological state of infectious cerebral edema, both integral and disassembled recipes inhibit LDH enzymes that have been over-activated, but the significant differences did not presented between both. Cinnabar and realgar in compound prescript provide the effects in various degrees on levels of LDH isoemzymas.
ABSTRACT
BACKGROUND: Angong niuhuang wan consists of mercury and arsenic, which has drawn the attention on its safety. It is necessary to carry on the research on evaluation in its availability and safety.OBJECTIVE: To study the mechanic differences of angong niuhuang wan in the organic body physiologically and pathologically.DESIGN: Randomized controlled experiment based on the experimental animals.SETTING: Institute of clinical pharmacology affiliated to a university.MATERIALS: The experiment was performed in Institute of Clinical Phar macology affiliated to Guangzhou University of Traditional Chinese Medicine from March to April in 2001. Guangdong Medical Experimental Animal Center provided 24 SD male rats, weighted varied from 250 g to 300 g.METHODS: SD rats were randomized into 4 groups, named as normal group, normal & angong niuhuang wan group(normal & wan group), model of cerebral infarction group(model group) (The middle cerebral artery embolism was induced in rats by photochemistry. ) and model of cerebral in farction group & angong niuhuang wan group (model & wan group), 6 rats in each group. Medication instruction: gastric feeding was applied once daily, 0. 13 g/kg, totally for 7 days. MAIN OUTCOME MEASURES: contents of lactate dehydrogenase (LDH) isoenzymes, LDH1-5.RESULTS: Contents of serum LDH1-3 in normal & wan group were significantly increased than those in normal group( P ＜ 0.01 ), of which, the values of LDH1, LDH2, LDH3 were(17.02 ±0.46)%, (14.70 ±0. 18)%,(15.47±0.13)% successively in normal & wan group, were(11.25 ± 0. 70) %, (8.26 ± 0. 90) %, ( 12. 86 ± 0.90) % successively in normal group. Content of serum LDH3[(15.51 ±2.60)% [ in model & wan group was significantly increased compared with that in model group[(10.93±2.10)% ] (P ＜ 0.01) . The contents of LDH4 were[(22.62 ±3.00)% ] and(28. 18 ±0. 80)% respectively in two groups, indicating significantly reducing( P ＜ 0.01 ).CONCLUSION: The organic injury of angong niuhuang wan is less in pathological state of focal cerebral infarction than that in physiological state,suggesting that the mechanic differences of angong niuhuang wan in organic body present in physiological and pathological states.
ABSTRACT
Objective To investigate the influence of blood arsenic concentration change on hepatic and renal function of rats administered with different toxic dosages of realgar by applying the linear mixed-effects model.Methods SD rats were given gastric gavage of realgar at the single dose of 3.738g/kg,1.869 g/kg and 0.935 g/kg respectively.After administration,the concentration of blood arsenic,the activities of urine alkaline phosphatase(AKP),N-acetyl-beta-D-glucosaminidase(NAG),serum glutamic oxaloacetic transaminase(GOT) and glutamate-pyruvate transaminase(GPT) activities,serum creatinine(Cr) level,and blood urea nitrogen(BUN) content were detected in different groups at different time points.The detection results were analyzed with the linear mixed-effects model.Results The changes of urine AKP and NAG activities,serum BUN content and serum GOT activity were presented in a dose-dependent manner,and had linear correlation with arsenic concentration.Conclusion In the dose range of 0.935 to 3.738 g/kg,realgar can cause the hepatic damage and the injury of tubular epithelial cells of kidney,but has not affected the renal excretion.
ABSTRACT
Objective To determine the content of six heavy metal elements of arsenicum(As),mercury(Hg),cuprum(Cu),plumbum(Pb),cadmium(Cd) and chromium(Cr) in Rhizoma Curcumae Longae.Methods Samples were digested with microwave digestion system,and the contents of Cu,Pb,Cd and Cr were determined by graphite furnace atomic absorption spectrometry(GFAAS);the contents of As and Hg were determined by atomic fluorescence spectrometry(AFS),and the reproducibility and recovery of the method were also examined.Results As and Hg contents in most of the products were below the limit.Only Cu,Pb and Cd contents exceed the limit.The recovery was 86.3 %～113.4 %and RSD was 10.4 %.Conclusions The method is simple and accurate,and can be used for the determination of heavy metal in Chinese herbs.
ABSTRACT
Objective:To investigate the different effects of Angong Niuhuang Wan on normal and pathological body. Methods:Cerebral infarct rat models were established by photochemically initiated thrombosis. The rats were randomly allocated to four groups. The control group and the model group were treated with 0.9%NaCl for seven days, and the control+drug group and the model+drug group with Angong Niuhuang Wan 0.13g/kg for seven days. Then amounts of idoenzymes of serum lactate dehydrogenase(LDH1～5) were determinated by the method of gel electrophoresis. Results:The amounts of LDH1 and LDH2 in the model group increase obviously as compared with the control group(P
ABSTRACT
Objective: To study the effect of Fructus Psoraleae on antipyrine elimination in rats. Methods:After the medication of Fructus Psoraleae decoction once daily for 6 days in a dose of 5. 3 g/kg, antipyrine was fed to rats in a dose of 400mg/kg. Concentration of antipyrine in various time was measured by HPLC, and the pharmacokinetics parameters of antipyrine elimination was caculated. Results: The elimination rate constant (Kel) of antipyrine in rats fed with Fructus Psoraleae decoction was 1.55 times more than that in the control group, and the elimination half - life (t1/2) was shortened by 60. 7 % . Conclusion: Fructus Psoraleae decoction accelerate the elimination of antipyrine in rats by inducing the activities of hepatic oxygenases.
ABSTRACT
Objective To study the pharmacokinetics of arsenic from Realgar in rats and tissue distribution after single dose and multiple dose of oral administration.Methods Rats were orally administrated with single dose(75 mg?kg~(-1)) and multiple dose (75 mg?kg~(-1)?d~(-1),one dose per day,15 continuous days) of Realgar respectively.Arsenic concen- trations in serum and arsenic contents in organs and tissues were determined by atomic spectrophotofluorimetry alter mi- crowave digestion pretreatment.PK Solutions 2.0~(TM) software was used to process experimental data.Results Half-life of absorption,distribution and elimination of arsenic in rat serum were 4.30,12.59 and 22.70 hours respectively after single dose administration.Arsenic concentration reached to maximum concentration (46.0?g?L~(-1)) at 3 hours after ad- ministration,and then decreased.Twelve hours after administration arsenic concentration increased to the second peak concentration (42.0?g?L~(-1)).When Realgar was orally administrated in a fixed close and at a fixed interval,arsenic concentration maintained a steady state from the 7th day after the first administration,and the half-life of elimination was 43.61 h.Arsenic could be detected in the main organs and tissues of rats after administration of a single dose.The ar- senic was most accumulated in the spleen,hair,lung and suprarenal gland organs,and kidney,heart,liver,bladder and skin came next.Brain,testis,muscle and tibia had the least amount of arsenic.After 15 continuous days of admin- istration,arsenic contents in kidney and bladder tissues increased appreciably besides suprarenal gland,lung,hair and spleen.After 2 weeks of discontinuation,arsenic contents in organs and tissues decreased by 21.1%～69.5 % except for heart.Conclusion Small amount of soluble arsenic in Realgar was absorbed in blood circulation.Absorption,distri- bution and elimination of arsenic from Realgar proceed slowly in rats after single dose of oral administration.Multiple dose of oral administration prolongs the elimination of arsenic.Arsenic distributes widely in rats organs and tissues.It is the first reported that high arsenic accumulation is found in the suprarenal gland,indicating that the suprarenal gland is prob- ably one of the target organs of Realgar.
ABSTRACT
Objective: To establish a method for determination of mercury (Hg) and arsenic (As) contents in biological samples. Methods: Biological samples containing Hg were pretreated with digestive agents of HNO3-H2SO4 and that of As with HNO3-HClO4 and HNO3-H2O2 under the pressure of 0.5 MPa,1.0 MPa and 1.5 MPa respectively heated for 2 minutes. And then the concentrations of Hg or As were determined by intermittent flow hydride generation-atomic spectrophotofluorimetry. Results: Recoveries of Hg and As were 97.3 %～99.1 %and 99.4 %～105.7 %respectively. Conclusion: The method is simple, rapid, accurate and sensitivite and with good reproducibility and is suitable for the determination of Hg and As contents in biological samples.