The Uptake and Distribution Evidence of Nano-and Microplastics in vivo after a Single High Dose of Oral Exposure

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after administration.Histopathology was performed to corroborate these findings.Results In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by histopathology.The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.

Tissue distribution of cadmium and its effect on reproduction in Spodoptera exigua

Vegetable fields are often contaminated by heavy metals,and Spodoptera exigua is a major vegetable pest which is stressed by heavy metals mainly by feeding.In this study,cadmium accumulation in the tissues of S.exigua exposed to cadmium and its effects on the growth and development of the parents and the offspring were investigated.Under the stress of different concentrations of cadmium(0.2,3.2,and 51.2 mg kg^(-1)),the cadmium content in each tissue of S.exigua increased in a dose-dependent manner.At the larval stage,the highest cadmium accumulation was found in midgut in all three cadmium treatments,but at the adult stage,the highest cadmium content was found in fat body.In addition,the cadmium content in ovaries was much higher than in testes.When F1S.exigua was stressed by cadmium and the F_(2)generation was not fed a cadmium-containing diet,the larval survival,pupation rate,emergence rate and fecundity of the F_(2)generation were significantly reduced in the 51.2 mg kg^(-1)treatment compared to the corresponding F1generation.Even in the F_(2)generation of the 3.2 mg kg^(-1)treatment,the fecundity was significantly lower than in the parental generation.The fecundity of the only-female stressed treatment was significantly lower than that of the only-male stressed treatment at the 3.2 and 51.2 mg kg^(-1)cadmium exposure levels.When only mothers were stressed at the larval stage,the fecundity of the F_(2)generation was significantly lower than that of the F1generation in the 51.2 mg kg^(-1)treatment,and it was also significantly lower than in the 3.2 and 0.2 mg kg^(-1)treatments.The results of our study can provide useful information for forecasting the population increase trends under different heavy metal stress conditions and for the reliable environmental risk assessment of heavy metal pollution.

Distribution of ^3H—nicotine in Rat Tissues Under the Influence of Simulated Microgravity

Rat tail suspension offers a useful model to reproduce physiologic responses to weightlessness.The present study was conducted in the head-down-tilt(HDT) rat model to assess changes in metabolism of body tissues employing 3H-nicotine. Twelve male rats were used in the study. Half of the rats were tail suspended at 30°for two weeks on a 12/12 light/dark cycle. During this period,body weight, food and fluid intakes were measured. At term, animals were anesthetized and injected IV withe a solution contaming 4 microuries of micotine. After 90 min the animals were sacrificed, exsanguinated and tissues (brain,blood,trachea,salivary gland,lung,heart,esophagus,spleen, kidneys and testes) were harvested. The distribution of 3H-nicotine per gram of each tissue was determinded and ealeulated as percent of total injected radioactivity. Final body weights of suspended ammals were significantly (P < 0.0 5) lower than those of eontrols(309±21 vs 350±11g). 3HNicotine waw retained in greatest amounts by the kindneys, followed inorder by salivary glands, spleen, and gastrointestinal tissues. compared to non-suspended control, the tissue retention of nicotine in suspended animals was decreased in the following tissues:esphyagus (25 %), aorta (25%). fundus (25%), trachea (22%), adrenals (18%), spleen (17 %), and pancreas (12 %). The decreased retention of mcotine in tissues from suspended animals may be indicative of the fluid shifts and changes in blood flow to those tissue beds. The lack of differnces in nicotine retention in liver and kidney between control and suspended groups may implicate a normal metabolic function of these organs even under simulated weightlessness.

Uptake,Depuration and Subcellular Distribution of Cadmium in Various Tissues of Perna viridis

Green-lipped mussels (Perna viridis) were collected from a local mariculture site and placed in pre-cleaned sea water tanks containing 0, 0.2, 0.5 and 1.3 μg/ml CdCl2. The level of Cd in the gill, viscera and gonad was measured. The concentration of Cd in the 3 tissues increased linearly over 4 days' of exposure. The rate of uptake depends on the concentration of Cd in the water. In the 3 tissues studied, the maximum rate of uptake (Vmax) was highest in the gill (500μg/g dry weight/day), followed by viscera (100μg/g dry weight/day) and gonad (56.8 μg/g dry weight/day). The majority of the Cd taken up was bound to a fraction of the heat-stable proteins similar to metallothioneins. The rate of Cd depuration from the tissues was poor. There was no change in Cd concentration over 8 days' depuration in clean water

Application of Gas Chromatography-mass Spectrometry in Analyzing Pharmacokinetics and Distribution of Deltamethrin in Miniature Pig Tissues

Objective To characterize the pharmacokinetics and distribution profiles of deltamethrin in miniature pig tissues by gas chromatography-mass spectrometry （GC-MS）. Methods Pharmacokinetics and distribution of deltamethrin in blood and tissues of 30 miniature pigs were studied by GC-MS after oral administration of deltamethrin （5 mg/kg bw）. Data were processed by 3P97 software. Results The serum deltamethrin level was significantly lower in tissues than in blood of miniature pigs.The AUC0-72 h, Cmax, of deltamethrin were 555.330±316.987 ng h/mL and 17.861±11.129 ng/mL, respectively. The Tmax, of deltamethrin was 6.004±3.131 h.Conclusion The metabolism of deltamethrin in miniature pigs is fit for a one-compartment model with a weighting function of I/C^2. Deltamethrin is rapidly hydrolyzed and accumulated in miniature pig tissues.

In vitro release of 1,3-bis(2-chloroethyl)-1-nitrosourea sustained-release microspheres and the distribution in rat brain tissues

BACKGROUND: The implantation of released chemotherapeutic drugs, which takes biodegradable polymer as vector, into the tumor site can get high concentration and release the drug for a long time, it can directly act on the tumor cells, and reduce the general toxicity. OBJECTIVE: To explore the in vitro and in vivo course of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sustained-release from BCNU-loaded polylactide (PLA) microspheres (MS) and location in rat brain tissue. DESIGN: A repetitive measurement. SETTING:Central Pharmacy, General Hospital of Chinese People’s Armed Police Forces. MATERIALS: Thirty male SD rats were used. PLA (Mr5000, batch number: KSL8377) was produced by Wako Pure Chemical Inc.,Ltd. (Japan); BCNU (batch number: 021121) by Tianjin Jinyao Amino Acid Co., Ltd.; BCNU-PLA-MS was prepared by the method of solvent evaporation and pressed into tablets (10 mg/tablet). High-performance liquid chromatography (HPLC) Agilent 1100 (USA); LS9800 liquid-scintillation radiometric apparatus (Beckman). Chromatographic conditions: Elite Hypersil ODS2 C18 chromatographic column (5 μm, 4.6 mm×150 mm); Mobile phase: methanol: water (50:50), flow rate was 1.0 mL per minute, wave length of ultraviolet detection was 237 nm, and the inlet amount of samples was 10 μL. METHODS: The experiments were carried out in the experimental animal center of the General Hospital of Chinese Armed Police from May 2004 to July 2005. ① In vitro BCNU-PLA-MS release test: BCNU-PLA-MS was prepared by the method of solvent evaporation, then placed in 0.1 mol/L phosphate buffered solution (PBS, pH 7.4, 37 ℃), part of MS were taken out at 1, 2, 3, 7, 10 and 15 days respectively, and the rest amount of BCNU in MS was determined by HPLC, then the curve of BCNU-PLA-MS release was drawn. ②In vivo BCNU-PLA-MS release and distribution test: The rats were anesthetized, then BCNU-PLA-MS were implanted to the site 1 mm inferior to the cortex of frontal lobe. Five rats were killed postoperatively at 4 hours, 1, 2, 3, 7 and 15 days, the residual MS was removed from the brain tissue. The rest amount of BCNU was determined with HLPC, and the curve of BCNU-PLA-MS release was drawn as compared with the amount of BCNU in the implanted tablets. Besides, brain tissues (1 g) at the implanted side and the contralateral one were obtained respectively, blood sample (0.5 mL) was also collected, 3H-BCNU was counted radioactively in radioactive liquid flash solution. The distributions of BCNU-PLA-MS in normal rat brain tissue and serum were detected. The analysis of variance was applied to compare the intergroup differences of the measurement data. MAIN OUTCOME MEASURES: ① Characteristics of BCNU-PLA-MS release in phosphate buffered solution (PBS) and rat brain tissue; ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum. RESULTS: ① Release of BCNU-PLA-MS in PBS and rat brain tissue: The BCNU released from BCNU-PLA-MS could be sustained for over 2 weeks both in PBS and brain tissue. In PBS, the released rate of BCNU was over 15% at 24 hours, nearly 50% at 72 hours and over 90% at 15 days. In brain tissue, the released rate was 8% at 4 hours, 16% at 24 hours, 60% at 72 hours, respectively, and BCNU could be sustained released for over 15 days. ② Distributions of BCNU-PLA-MS in normal rat brain tissue and serum: The concentrations of BCNU in the ipsilateral brain tissue were 6 to 70 times higher than those in the contralateral one. The concentrations of BCNU in the ipsilateral brain tissue were obviously higher than those in serum and contralateral brain tissue (F =103.47, P < 0.01). CONCLUSION: BCNU-PLA-MS can increase the drug concentration in targeted brain tissue, decrease that in the non-targeted brain tissue, reduce general toxic and side effects, and have good releasing function.

Determination of 6258-70,a new semi-synthetic taxane,in rat plasma and tissues:Application to the pharmacokinetics and tissue distribution study

Cancer is the leading cause of death all over the world.Among the chemotherapy drugs,taxanes play an important role in cancer treatment.6258-70 is a new semi-synthetic taxane which has a broad spectrum of antitumor activity.A fast and reliable high performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS） method was developed for quantification of 6258-70 in rat plasma and tissues in this paper.After extraction by liquid-liquid extraction method with methyl tert-butyl ether,the samples were separated on a Kinetex C_（18） column（50 mm × 2.1 mm,2.6 μm,Phenomenex,USA） within3 min.The method was fully validated with the matrix effect between 87.7%and 99.5%and the recovery ranging from 80.3%to 90.1%.The intra- and inter-day precisions were less than 9.5%and the accuracy ranged from-3.8%to 6.5%.The reliable method was successfully applied to the pharmacokinetics and tissue distribution studies of 6258-70 after intravenous administration in rats.The pharmacokinetic results indicated that the pharmacokinetic behavior of 6258-70 in rats was in accordance with linear features within tested dosage of 1 to 4 mg/kg,and there was no significant difference between the two genders.The tissue distribution study showed that 6258-70 had an effective penetration,spread widely and rapidly and could cross blood-brain barrier.The results of pharmacokinetics and tissue distribution may provide a guide for future study.

Development and Validation of UHPLC-MS/MS Method for Quantifying of Agarotriose:An Application for Pharmacokinetic,Tissue Distribution,and Excretion Studies in Rats

A sensitive,rapid,and robust ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)method was established for the first time to quantify agarotriose(A3)in rat plasma,tissues,urine,and feces.A3 and stachyose(internal standard)were separated by a BEH amide column at 65℃under the mobile phase of 10 mmol L^(-1)ammonium ace-tate-acetonitrile(42:58,v/v)with 350µLmin-1.The acquisition of transitions was carried out in multiple reaction monitoring(MRM)pattern operating with positive ionization at m/z 509.16>329.15 for A3 and m/z 689.15>527.11 for stachyose.The linearity ranges of A3 were 10 to 5000nmolL^(-1)for plasma,20 to 10000nmolL^(-1)for tissues,and 40 to 20000nmolL^(-1)for urine and feces.The accuracy and precision ranged from 90.9%to 111.6%and 0.7%to 10.1%,respectively.The stability was between 86.1%and 102.5%.The extraction recovery was consistent and reproducible.The matrix effect ranged from 1.5%to 11.4%.The pharmacokinetic,tissue dis-tribution,and excretion studies were successfully conducted with the validated method.Results showed that A3 could be absorbed by rats,and the absolute bioavailability was 6.7%.Furthermore,it was rapidly distributed in rat tissues and mainly eliminated via feces excretion(67.0%)after oral administration.For intravenous bolus,85.5%was recovered,and renal excretion was the primary path-way(77.6%)for cumulative recovery.

Androgen receptors are expressed in a variety of human fetal extragenital tissues： an immunohistochemical study

Aim： To investigate the expression of androgen receptors in the extragenital tissues of developing human embryo. Methods： Using immunohistochemistry, we investigated the distribution of androgen receptor （AR） in the extragenital tissues of paraffin-embedded tissue sections of first trimester （8-12 weeks gestation） human embryos. Gender was determined by polymerized chain reaction. Results： There were no differences in the expression and distribution of AR in male and female embryos at any stage of gestation. AR expression was seen in the thymus gland. The bronchial epithelium of the lungs showed intense positive staining with surrounding stroma negative. Furthermore, positive staining for androgen receptor was exhibited in the spinal cord with a few positive cells in the surrounding tissues. Cardiac valves also showed strong positive staining but with faint reactivity of the surrounding cardiac muscle. There was no staining in kidney, adrenal, liver or bowel. Conclusion： This study demonstrates that immunoreactive AR protein is present in a wide variety of human first trimester fetal tissues and shows the potential for androgen affecting tissues, which are mostly not considered to be androgen dependent. Moreover, it implies that androgen might act as atrophic factor and affect the early development of these organs rather than simply sexual differentiation.

Tissue Distribution of [^3H]—Nicotine in Rats

This study was conducted in adult male Sprague -- Dawley rats to determine the distribution of [3H]-nicotine in blood and tissues following a bolus injection and a constant infusion of pure nicotine. The animals were anesthetized and injected with either 0.5 ml of nicotine solution or given a constant infusion of the same nicotine solution with identical amounts of radioactive nicotine. After sacrifice, blood, brain, trachea, salivery gland, esophagus, lung, heart, liver, fundus, antrum, spleen, pancreas, duodenum, jejunum, ileum, cecum, colon, kidneys, adrenal gland, and testes were collected and measured for radioactivity by scintillation counting. The distribution of nicotine was found highest in kidneys by both routes of administration. Higher accumulations were also found in salivary and adrenal glands, fundus, antrum, duodenum, jejunum, ileum and colon. Retention of nicotine via constant infusion was significantly higher in esophagus, fundus antrum, spleen, cecum, pancreas, testes, heart and muscle when compared with bolus injection. Six-fold increase in retention of blood levels of nicotine were found with constant infusion. (P<0.05). The results indicate that longer retention of nicotine occurs in blood and other specific tissues such as esophagus, fundus, antrum, spleen, cecum, pancreas, testes, heart and muscle via constant exposure. These data may implicate the predisposition of these tissues to pathologic manifestations.

Comparative Studies of Substrate and Inhibitor Specificity of Glutathione S-Transferases in Six Tissues of Oxya chinensis(Thunberg)(Orthoptera:Acrididae)

Specific activity, substrate specificity, and kinetic parameters （Km and Vmax） of glutathione S-transferases （GSTs） towards three substrates, 1-chloro-2,4-dinitrobenzene （CDNB）, 1,2-dichloro-4-nitrobenzene （DCNB）, and p-nitrobenzene chloride （pNBC） were investigated in six tissues （foregut, midgut, hindgut, fat body, hemolymph, and muscle） of Oxya chinensis. In addition, the inhibition in vitro （ethacrynic acid, and Cibacron Blue 3GA） of Oxya chinensis in the six tissues was also investigated. Glutathione S-transferase activity was detected in all the six tissues examined. The rank order of GST activities towards CDNB was fat body 〉 midgut 〉 hindgut 〉 muscle 〉 foregut 〉 hemolymph both in females and males. Glutathione S-transferase activities in the fat body in females and males were 1.3- to 10.4-fold and 1.1- to 10.0- fold higher than those in the other tissues. The rank order of GST activities towards the other substrates changed slightly. From these results, it was inferred that GSTs in the fat body and midgut played important roles in detoxifying xenobiotics including insecticides and plant allelochemicals in O. chinensis. In the three substrates examined, CDNB seemed to be the best substrate, followed by pNBC and DCNB. The kinetic parameters of GSTs were different among the six tissues. This suggested that GSTs in different tissues have various affinities and catalytic efficiency to substrates. In vitro inhibition study showed that the median inhibition concentration （IC50） values of the two inhibitors to GSTs from the six tissues were different. The results suggested that the two inhibitors have different inhibition potency to GSTs from the different tissues. The observed changes in kinetic parameters and inhibition in vitro among the six tissues of the insect might suggest that the number and structure of isoenzymes and their rate of expression varied for the different tissues.

Pharmacokinetics and Tissue Distribution of Clevidipine and Its Metabolite in Dogs and Rats

The purpose of the current study was to examine the pharmacokinetic profiles and tissue distribution of clevidipine, an ultra-short-acting calcium antagonist in Beagle dogs and Sprague-Dawley rats, respectively. The pharmacokinetics and biodistribution of its primary metabolite H 152/81 were also evaluated. Dogs received intravenous infusion of clevidipine at a dose rate of 17 μg/（kg·min）, and rats were given intravenous administration of clevidipine at a dose of 5 mg/kg. Dog plasma and rat tissues were collected and assayed by HPLC-MS/MS. It was found that plasma clevidipine quickly reached the steady state concentration. The terminal half-life was short （16.8 min）, pointing out a rapid elimination after the end of the infusion. The total clearance was 5 mL/（min·kg）. In comparison, plasma concentra- tion of H152/81 was increased more slowly and was significantly higher than that of clevidipine. After intravenous administration, clevidipine was distributed rapidly into all tissues examined, with the high- est concentrations found in the brain, heart and liver. Maximal concentrations of clevidipine were found in most tissues at 10 min post-dosing. However, the proportion of clevidipine distributed in all tissues was quite small （0.042‰） compared to the total administration dose. It was suggested that clevidipine was mainly distributed in blood and it transformed to inactive metabolite raoidlv.

Absolute bioavailability,dose proportionality,and tissue distribution of rotundic acid in rats based on validated LC-QqQ-MS/MS method

Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C_(18) column(4.6mm×50mm,5μm)under gradient conditions with eluents of methanol:acetonitrile(1:1,V/V)and 5mM ammonium formate:methanol(9:1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30→437.30 for RA and m/z 256.10→227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40mg/kg)and intravenous(10mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.

Herb-drug interaction in the protective effect of Alpinia officinarum against gastric injury induced by indomethacin based on pharmacokinetic, tissue distribution and excretion studies in rats

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis, abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects. However, the role of herb-drug interaction between indomethacin and A. officinarum based on pharmacokinetic, tissue distribution and excretion still remains unknown. In this study, an ultra-fast liquid-tandem mass spectrometry(UFLC-MS/MS) method was developed for simultaneous determination of indomethacin and its three metabolites, O-desmethylindomethacin(ODI), deschlorobenzoylindomethacin(NDI) and indomethacin acyl-b-D-glucuronide(IDAbG) by oral administration of indomethacin solution with and without the ethanolic extract of A. officinarum and applied to comparative pharmacokinetic, tissue distribution and excretion studies. Our results clarified that oral administration of A. officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin. And the pharmacokinetic interaction between indomethacin and A. officinarum reduced the systemic exposure of indomethacin and increased its elimination. Tissue distribution results demonstrated that co-administration of A. Officinarum could not reduce the accumulation of indomethacin in the target tissue of the stomach, but could accelerate the excretions of indomethacin and its three metabolites including ODI, NDI and IDAb G in the bile and feces of rats in the excretion study.Therefore, A. Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

Disposition and Tissue Distribution of ML12 in Rats

To investigate the disposition and tissue distribution of ML12 after intravenous （iv） administration in rats, the compound in plasma or in tissue was extracted into ethyl acetate under basic condition and was determined by HPLC after extracted by dilute sulfuric acid. Excitation wavelength and emission wavelength of fluorescence detection were 278 nm and 307 nm, respectively. The data were processed with the software 3P97 to calculate the main pharmaceutical parameters of ML12. At dose of 5 and 10 mg/kg, the elimination of the drug from plasma was found to be kinetically linear, but when the dosage was 20 mg/kg, a non-linear feature was observed. The highest level of ML12 was found in the kidney. Distribution of ML12 after iv administration was extensive and the concentration-time profile was found to be fitted to an open two-compartment model.

Pharmacokinetic Study and Tissue Distribution of Single Mangiferin After Intravenous Administration in Rats

A simple, sensitive ane selective high performance liquid chromatographic （HPLC） method with UV detection （320 nm） was developed and validated for determination of mangiferin in rat plasma and tissues. Mangiferin and internal standard （spinosin） were separated using mobile phase of acetonitrile-water （20：80, v/v） with 1% glacial acetic acid and 1% THF on a Phenomenex gemini C18 column. The flow rate was 0.7 mL/min. The calibration curves of mangiferin in plasma and tissues were linear over the investigated ranges. The intra- and inter-run preeisions for all samples were less than 13.8 %. The time-concentration curve of mangiferin after intravenous administration to rats corresponded to two-compartment model. The main pharmacokinetic parameters T0.5α, T0.5β, CL and AUC0-T were 15.87 min, 26.15 rain, 6.1 L/（min·kg） and 3.28 mg· min/mL, respectively. The highest and lowest levels of mangiferin occurred in spleen and brain, respectively. Mangiferin was not found in liver. After intravenous administration, the drug was distributed extensively and transferred quickly in rats in vivo.

Diazinon Toxicokinetics, Tissue Distribution and Anticholinesterase Activity in the Rat

The toxicokinetics, tissue distribution, and anticholinesteruse (antiChE ) activity of diazinon were investigated in the rat. Plasma concentrations most adequately fitted a two-compartment open model after iv administration of 10 mg/kg and a one-compartment model after oral administration of 80 mg/kg. Diazinon elimination half-life following iv and oral dosing was 4.70 and 2.86 h, respectively. The oral bioavailabllity was found to be low (35.5%). Hepatic extraction ratios after iv administration of 5 or 10 mg

Tissue distribution of Lycium barbarum polysaccharides in rat tissue by fluorescein isothiocyanate labeling

To date, in vivo investigations of polysaccharide’s pharmacokinetics are significantly restricted by the difficulty in their detection. This study was conducted to establish the quantitative determination of Lycium barbarum polysaccharides(LBPs) based on fluorescein isothiocyanate(FITC) pre-labeling and to investigate their tissue distribution in rat. We obtained the calibration curves linear over the range of 0.0–25 μg/m L in rat tissue samples with correlation coefficients greater than 0.99. The inter-day and intra-day precisions(RSD, %) were within 15%, and the relative recovery ranged 95.2%–102.4%, with RSD range 1.48%–9.58%, indicating that this experiment was suitable for the determination of LBPs. The fluorescence intensity was measured after 24 h storage at room temperature, 3 times of freeze-cycle and cryopreservation at –20 ℃ for 15 day, these results indicated that the stability of the samples was good. LBP-FITC was mainly absorbed by the small intestine and stomach, and mainly excreted in the urine through the kidney;this distinct difference in the tissue distribution of LBPs could be attributed to the size of these LBPs in relation to the pore sizes of the vascular beds in the kidney and liver. Results showed in this study enable us to comprehensively understand the biological effects of LBPs following its oral ingestion.

Time Dependent Tissue Distribution of ^(203)Hg in the White Rat and Anabas testudineus, a Freshwater Teleost

The distribution of mercury, an environmentally important toxicant, has been evaluated in a time dependent manner in different tissues of white rat and a freshwater teleost, Anabas testudineus. Sampling was performed at 15 min, 2, 6 and 48 h post injection (im) of 203Hg mercuric nitrate. Radioactivity of the 5% tissue homogenate, serum and bile was measured in a Gamma Counter. The rate of 203Hg accumulation is higher in fish immediately after administration which, however, is more or less of equal rate in the later period of observation in both the experimental animals. Partitioning of 203Hg occurs in a species specific manner with higher levels recorded in the brain and gonad of white rat. Spleen, liver and kidney, however, are the major tissues to accumulate mercury in both the species. The present study highlights that kidney is the target site of mercury retention with a higher kidney/liver ratio of mercury.

Tissue distribution of deoxynivalenol in piglets following intravenous administration

Contamination of deoxynivalenol（DON） in grains is common worldwide and pigs are particularly susceptible to this mycotoxin. The distribution of DON in porcine tissues following intravenous administration was investigated in this study. Fifteen pigs were randomly divided into three groups. Animals in groups A and B were administrated with DON at the dose of 250 and 750 μg kg–1 body weight, respectively, while group C served as blank control. Plasma, bile and 27 tissues were collected at 30 min post-administration. DON concentrations in all samples were tested using high-performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS）. To observe the distribution of DON in tissues, these samples were further subjected to the immunohistochemical analyses. Totally, the bile and 13 tissues were sampled for DON-based detection, including kidney, mesenteric lymph nodes, muscle, stomach, jejunum, colon, plasma, spleen, rectum, cecum, liver, ileum, and duodenum. No significant difference was observed for the concentrations of DON in duodenum, ileum and liver samples between groups A and B; while the DON concentrations in cecum and rectum of group B were significantly higher（P-value 〈0.05） than those in group A. In addition, the DON concentrations in stomach, jejunum, colon, mesenteric lymph nodes, muscle, kidney, spleen, bile, and plasma of group B were remarkably higher than those of group A（P-value〈0.01）. Levels of DON in other 14 tissues including medulla oblongata, midbrain, diencephalon, pons, tip and tongue body, tongue, soft palate, tonsils, pharyngeal mucosa, oral buccal mucosa, thymus, thyroid, esophagus and adrenal gland were all below the limit of detection. The results of immunohistochemistry showed that 11 tissue samples（medullaoblongata, tonsil, adrenal medulla, thyroid gland, thyroid, stomach, duodenum, jejunum, kidney, spleen, and mesenteric lymph nodes） were positive and DON was mainly distributed around blood vessels in these tissues. Therefore, we believed that concentrations of DON in tissues differ when pigs are in exposure to various dosages and DON causes lesions in many pig tissues.