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<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
Objective To explore the optimal method of extraction and determination of rhynchophylline and isorhynchophylline in Ramulus Uncariae cum Uncis. Methods A RP-HPLC was performed on a Phenomenex C18 column (4. 6 mm× 150 mm, 5m) at 30℃. The mobile phase consisted of methanol-0. 01 mmol/L triethylamine solution (70: 30, pH 7.0 adjusted by glacial acetic acid) at the flow rate of 0. 5 mL/min. The automatic sample injector was set at 5℃ and the ultraviolet detector was operated at 245 nm. And then, the effect of different extraction condition on the contents of rhynchophylline and isorhyn-ehophylline in Ramulus Uncariae cum Uncis was investigated. ResultsA good linearity of rhynchophylline was in the range of 2. 5μg/mL to 80. 0μg/mL (Y=76. 7170X-0. 0727,r=0. 999 8),the average recoveries were from 99. 84 ％ to 116. 91％, and the RSD (n=6) were less than 8.8 ％. A good linearity of isorhynchophylline was in the range of 2. 0 μg/mL to 80. 0 μg/mL (Y=87. 4729X-0. 3666, r=0.999 7), the average recoveries were from 87.08 ％ to 104. 97 ％, and the RSD (n=6) were less than 7.3 ％. The contents of rhynchophylline and isorhynchophylline in the methanol-extracted solu- tion were approximately ten times as much as those in water-decocted solution. The main factors which had effect on the ex-traction of rhynchophyUine and isorhynchophylline in methanol solution were supersonic time,methanol amount and cold-dousing time, in a decreasing sequence. The best condition selected by orthogonal experiment wasb as follows: extracting the medicinal material with 20-fold volumes of methanol, cold maceration for 24h and supersonic extraction for 1 h. Conclusion The extraction percentage of rhynchophylline and isorhynchophylline in the extraction condition of cold maceration with methanol and supersonic extraction is superior to that in the water-decocting condition. The method is simple, fast and accurate, and it can be used for the quality control of Ramulus Uncariae cum Uncis.
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[Objective] To compare the antipyretic and anti-inflammatory actions and acute toxicity between Chuanxinlian Soft Capsules (CSC) and Chuanxinlian Tablets. [Methods] Antipyretic action of CSC was observed on rabbit fever models induced by lipopolysaccharide (LPS) and rat fever models induced by baker's yeast. Rat models with pedal swelling induced by carrageenin, mouse models with auricle swelling induced by dimethylbenzene and mouse models with celiac capillary hyperpermeability induced by acetic acid were used to observe the anti-inflammatory action oi CSC. Its acute toxicity in mice was also evaluated. [Results] High- and moderate-dose CSC reduced fever in rabbits induced by LPS (P 0.05). High-, moderate- and low-dose CSC has an inhibitory effect on acute inflammatory exudation (P
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OBJECTIVE: To observe the therapeutic effect of Wuling Powder extract on rats with renal hypertension and to evaluate the influence of it on the volume of urine and the concentrations of Na(+), K(+), Cl(-). METHODS: Reformed Gold-blatt hypertension rat model (G-2K1C) was established. The rats were divided into 6 groups as follows: sham-operation group; model group, Wuling Powder high dosage group (80 g/kg), Wuling Powder middle dosage group (40 g/kg), Wuling Powder low dosage group (20 g/kg), and hydrochlorothiazide (HCT) group (25 mg/kg). Urine volume of the rats was measured during the experiment. Tail arterial pressure and [Na(+)], [K(+)], [Cl(-)] in serum of the rats were detected after 30 days of treatment. RESULTS: The blood pressure of the G-2K1C rats was decreased in the three Wuling Powder groups (P0.05). Diuretic effect of the three dosages of Wuling Powder was weaker than that of the HCT (P0.05), but [K(+)] of the HCT group was significantly decreased compared with that of the false-operation group and the three Wuling Powder groups (P<0.01). CONCLUSION: Wuling Powder extract had satisfying therapeutic effects in increasing the discharge of urine, decreasing the blood pressure and keeping the balance of the serum electrolyte contents in rats with renal hypertension.
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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.
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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.
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Objective To observe the protective effects of the extracts of Rhizoma Zingiberis and Pericarpium Citri Reticulatae on myocardial ischemia reduced by isoproterenol(ISO) in rats,and to explore their optimal ratio.Methods Acute myocardial ischemia rat model was established by continuously subcutaneous injection of large-dose.Then the content of the serum creatine kinase(CK) within 24 hours in rats were detected,and the optiaml ratio of Rhizoma Zingiberis and Pericarpium Citri Reticulatae was optimized by uniform design.Results Compared with the control group,the content of CK in the model group was significantly increased(P
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Objective To study the effect of compatibility of Flos Carthami and Semen Persicae in different ratios on the contents of hydroxysafflor yellow A(HSYA) in their water decoction.Methods Reverse-phase HPLC was performed on a Luna C18 column(4.6 mm?150 mm,5?m) at 30℃.The mobile phase consisted of methanol-0.12 mmol?L-1 phosphate solution(28∶72,V/V) at the flow rate of 1.0 mL? min-1.The detector was operated at wavelength of 403nm.Results A good linearity of HSYA was obtained in the range of 4.0～160.0?g?mL-1(Y=25 396X+40 247,r=0.999 7),the average recovery was 94.76% and the RSD(n=6) was 2.93%.The amount of HSYA increased with the ratio of Flos Carthami,but had no correlation with the ratio of Semen Persicae.Conclusion The HPLC method for determination of HSYA is simple,fast and accurate.It can be used for the quality control of Flos Carthami and its compound preparations.Semen Persicae has no effect on the extraction of HSYA.
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Objective: To observe the difference between borneol-induced opening of blood-brain barrier (BBB) and its pathological opening . Methods: The expression of inducible nitric oxide synthetase (iNOS) in brain microvascular endothelial cells in normal rats and brain-injury rats before and after treatment of borneol was examined by immunohistochemical methods with S-P staining and iNOS antibody. Results: iNOS expression was not different in normal rats before and after treatment. However, iNOS expression was increased in brain-injury rats and borneol could inhibit the expression of iNOS. Conclusion: Borneol-induced opening of BBB is different from pathological opening of BBB. Borneol can increase the pathological opening of BBB and has a protective effect on brain tissue.
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The concentrations of borneol in the serum and brain tissue of rats were determined by gas chromatography. Using brain tissue as a relatively independent system, PHARMFIT and PCNONLIN softwares are applied for the kinetic analysis of the infracorporal process of borneol in order to find out and compare the pharmacokinetic characteristics of borneol in the brain and serum. The results showed that borneol was absorbed very rapidly in the gastrointestinal tract and readily permeates the blood-brain barrier into brain tissue. There was a higher specific value of borneol concentration in the brain and serum. Moreover, the half life of distribution phase of borneol in the brain was three times higher than that in the serum. But the constants of elimination rate of borneol in the brain and serum decreased simultaneously and parallelly, hence the accumulation of borneol in brain will not be found.
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Objective To observe the effect of Xiaochaihu decoction(XCD) on experimental endometriosis in rats.Methods Rat models of endometriosis were established and the effect of XCD were evaluated by measuring the volume of ectopic endometrium (EE) and its ultrastructure with transmission electron microscopy.Results After treatment,moderate and high-dosage of XCD(10g/kg and 15g/kg respectively) could markedly inhibit endometrial explant growth and decrease the volume of EE(P 0.05).Meanwhile,the glandular cells in the endometrium after treatment in the moderate and high-dosage groups showed characteristic features of apoptosis:cellular atrophy,condensation of cytoplasm and nuclear chromatin and increase of their density,occurrence of the intercellular apoptotic bodies as well as degeneration and necrosis of stromal cell.Conclusion XCD has obvious effects in inhibiting ectopic endometrium and its mechanism may be related to the reduction of cell death (including apoptosis and necrosis) by regulating the immune function.