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The LQFM05 is a prototype drug designed for treatment of psychiatric disorders, such as schizophrenia, exhibiting anxiolytic- and antidepressant-like (12 or 24 µmol/kg) effects in classical behavioral tests. In order to evaluate its pharmacokinetic properties, a liquid chromatography method coupled to a quadrupole time of flight mass spectrometry system (LC-QTOF/MS) was developed and fully validated for LQFM05 analysis in rat plasma and tissue samples (brain, heart, liver, and kidneys). Liquid-liquid extraction, solid phase extraction and protein precipitation were assessed as clean-up procedures for biological samples and analyte enrichment. Plasma and tissue samples underwent protein precipitation as a preliminary step, using acetonitrile. Linearity was fully demonstrated for the dynamic range (10.0 to 900.0 ng/mL), with r2 values higher than 0.99 (RSDslope ≤ 2%, Fcal < Ftab, Ccal < Ctab). Biodistribution studies in rats revealed high brain tissue concentrations (12.4 µg/g), suggesting elevated drug affinity to the main therapeutic target tissue, showing a blood partition coefficient of 1.9. Kidneys also showed great exposure and tissue affinity, suggesting a potential extrahepatic clearance. Likewise, all examined tissues exhibited satisfactory LQFMF05 distribution. The mass fragmentation spectrum indicated the presence of its main metabolite, LQFM235, yielded by high hepatic hydroxylation route, an equally bioactive derivative. Lastly, the developed LC-QTOF/MS method was shown to be sensitive (LOQ = 10 ng/mL), precise and accurate for LQFM05 determination in tissue homogenates and plasma samples.
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Cutibacterium acnes has been associated with chronic prostatitis, which can potentially favor the appearance of tumors in the prostate. Prostatitis is difficult to treat, and the drug needs to be able to penetrate the prostate. The aim was to investigate the pharmacokinetics of clindamycin in the interstitial fluid of rat prostate using microdialysis. Microdialysis probes were recovered in vitro and in vivo. Clindamycin was administered at 80 mg/kg iv bolus for plasma and tissue pharmacokinetic experiments. A microdialysis probe was implanted in the prostate gland for collections over an 8-hour period. The pharmacokinetic parameters were determined by both compartmental and non-compartmental approaches. Penetration was determined as the ratio between the area under the curve and the time of the clindamycin measurement in the prostate. The recovery of the in vivo probes was 38.11 ± 1.14%. The plasma profile was modeled by a two-compartment pharmacokinetic model. Clindamycin presented a prostate/plasma ratio of 1.02, with free concentrations above the minimum inhibitory concentration for Cutibacterium acnes isolates. This was the first study that determined clindamycin free concentrations in the prostatic fluid of rats. These findings suggest that clindamycin may be an effective alternative for the treatment of prostatitis caused by Cutibacterium acnes.
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Clindamicina , Prostatite , Animais , Antibacterianos/farmacologia , Clindamicina/farmacologia , Clindamicina/uso terapêutico , Masculino , Testes de Sensibilidade Microbiana , Próstata , Prostatite/tratamento farmacológico , RatosRESUMO
Numerous studies have demonstrated that Radix Astragali can inhibit gastric ulcers in mice. Anhydrous ethanol (0.01 mL/g) administered to mice by intragastric infusion can induce gastric ulcer injury. This study was performed to compare the stomach tissue distribution profiles of four major bioactive constituents of Radix Astragali(calycosin-7-O-ß-d-glucoside, calycosin, ononin and formononetin) after oral administration of extract of Radix Astragali (ERA)in normal and gastric ulcer mice. The abundance of Radix Astragali constituents was determined using an ultra-pressure liquid chromatograph with a photodiode array detector (UPLC-PDA), after which histograms were drawn. In comparison with normal mice, the contents of calycosin- 7-O-ß-d-glucoside, calycosin, ononin and formononetin in the stomach tissue samples of gastric ulcer mice showed significant differences at the selected time points (P < 0.05).The abundance of each of the four tested constituents in the normal groups was higher than that of the gastric ulcer groups. This study provides an empirical foundation for future studies focused on developing clinical applications of Radix Astragali
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Animais , Masculino , Feminino , Camundongos , Estômago/efeitos dos fármacos , Úlcera Gástrica/patologia , Tecidos/efeitos dos fármacos , Distribuição Tecidual , Astrágalo/efeitos adversos , Plantas Medicinais , Administração OralRESUMO
Abstract Background: Chronic heart failure (CHF) is a complex syndrome which comprises structural and functional alterations in the heart in maintaining the adequate blood demand to all tissues. Few investigations sought to evaluate oxidative DNA damage in CHF. Objective: To quantify the DNA damage using the comet assay in left ventricle (LV), lungs, diaphragm, gastrocnemius and soleus in rats with CHF. Methods: Twelve male Wistar rats (300 to 330 g) were selected for the study: Sham (n = 6) and CHF (n = 6). The animals underwent myocardial infarction by the ligation of the left coronary artery. After six weeks, the animals were euthanized. It was performed a cell suspension of the tissues. The comet assay was performed to evaluate single and double strand breaks in DNA. Significance level (p) considered < 0.05. Results: The CHF group showed higher values of left ventricle end-diastolic pressure (LVEDP), pulmonary congestion, cardiac hypertrophy and lower values of maximal positive and negative derivatives of LV pressure, LV systolic pressure (p < 0.05). CHF group showed higher DNA damage (% tail DNA, tail moment and Olive tail moment) compared to Sham (p < 0.001). The tissue with the highest damage was the soleus, compared to LV and gastrocnemius in CHF group (p < 0.05). Conclusion: Our results indicates that the CHF affects all tissues, both centrally and peripherically, being more affected in skeletal muscle (soleus) and is positively correlated with LV dysfunction.
Resumo Fundamento: A insuficiência cardíaca crônica (ICC) é uma síndrome complexa que compreende alterações estruturais e funcionais no coração, mantendo demanda sanguínea adequada a todos os tecidos. Poucas investigações procuraram avaliar o dano oxidativo ao DNA na ICC. Objetivo: Quantificar o dano ao DNA utilizando o ensaio cometa no ventrículo esquerdo (VE), pulmões, diafragma, gastrocnêmio e sóleo em ratos com ICC. Métodos: Doze ratos Wistar machos (300 a 330 g) foram selecionados para o estudo: placebo (n = 6) e ICC (n = 6). Os animais foram submetidos a infarto do miocárdio através de ligadura da artéria coronária esquerda. Após seis semanas, os animais foram sacrificados. Foi realizada uma suspensão celular dos tecidos. O ensaio cometa foi realizado para avaliar as quebras de fita simples e dupla no DNA. Nível de significância (p) < 0,05. Resultados: O grupo ICC apresentou maiores valores de pressão diastólica final do ventrículo esquerdo (PDFVE), congestão pulmonar, hipertrofia cardíaca e menores valores de derivados máximos positivos e negativos da pressão do VE, pressão sistólica do VE (p < 0,05). O grupo ICC apresentou maior dano ao DNA (% de DNA da cauda, momento da cauda e momento da cauda de Olive) em comparação ao placebo (p < 0,001). O tecido com maior dano foi o sóleo, comparado ao VE e ao gastrocnêmio no grupo ICC (p < 0,05). Conclusão: Nossos resultados indicam que a ICC afeta todos os tecidos, de maneira central e periférica, sendo mais afetada no músculo esquelético (sóleo) e está positivamente correlacionada com a disfunção do VE.
Assuntos
Animais , Masculino , Dano ao DNA/genética , Insuficiência Cardíaca/genética , Valores de Referência , Ratos Wistar , Estresse Oxidativo , Músculo Esquelético/patologia , Ensaio Cometa , Análise de Célula Única , Insuficiência Cardíaca/patologia , Ventrículos do Coração/patologia , Hemodinâmica , Fígado/patologia , Pulmão/patologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologiaRESUMO
ABSTRACT This study was designed to explore the pharmacokinetic regularity of the plasma concentration, tissue distribution and excretion of orcinol glucoside from aqueous extracts of raw and processed Curculigo orchioides Gaertn., Hypoxidaceae. The experiment first used an ultrahigh-performance liquid chromatography-tandem mass spectrometry approach with multiple reaction monitoring and a positive mode to separate orcinol glucoside from naringin to obtain the plasma concentration curves, bar graph of tissue distribution and excretion curves. These results might be beneficial for reasonable clinical application of C. orchioides and for further development of its wine and salt-processing mechanism.
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Concentration of essential (Se, Zn and Cu) and non-essential (As, Cd, Hg and Pb) trace elements were measured in selected tissues of two dead whale sharks (Rhincodon typus) stranded in the Gulf of California (GC) in 2017 and 2018. Concentrations of Cd and Pb in the skeletal muscle of the whale shark from La Paz Bay, GC were higher compared to a previous study on whale shark from China. The shark from La Paz Bay also presented higher concentration of Pb in the epidermis, compared to the same tissue of the other whale shark stranded in Punta Bufeo, GC. The Hg in all analysed tissues was lower than those documented in carnivorous sharks. Molar ratio Se:Hg shows an excess of Se over Hg in all the tissues sampled in both sharks.
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Monitoramento Ambiental/métodos , Epiderme/química , Metais Pesados/análise , Músculo Esquelético/química , Tubarões/metabolismo , Oligoelementos/análise , Poluentes Químicos da Água/análise , Animais , Baías/química , México , Oceano PacíficoRESUMO
The aim of this study was to determine the distribution of cadmium (Cd) and lead (Pb) in muscle and liver tissue of Haemulopsis axillaris and Diapterus peruvianus from the Eastern Pacific in Mexico and to assess the health risk to consumers. Fish were collected as bycatch on the continental shelf between the coasts of Sinaloa and Guerrero (Eastern Pacific). Cd and Pb were quantified in muscle and liver tissue using graphite-furnace atomic absorption spectrophotometry (GF-AAS).Concentration of Cd was greater in muscle tissue than in liver tissue; with Pb, however, the opposite pattern was found. The highest concentration of Cd (0.177 µg g-1) was found in muscle tissue of H. axillaris from Sinaloa. For Pb, the highest level (0.692 µg g-1) was found in the liver tissue of H. axillaris also from Sinaloa. Levels of Cd and Pb in muscle tissue were both below Mexican Guidelines (0.5, 1.0 µg g-1 wet weight for Cd and Pb respectively) and International Guidelines. The hazard index (HI) for both metals in the edible portion of studied considering metal levels in the edible portion and the rate of fish consumption by the Mexican population (in adults and children) was less than 1 (HI < 1), values which do not represent a health risk to consumers.
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Cádmio/análise , Peixes/metabolismo , Chumbo/análise , Músculos/metabolismo , Poluentes Químicos da Água/análise , Animais , Cádmio/química , Criança , Humanos , Chumbo/química , México , Medição de Risco , Espectrofotometria Atômica , Poluentes Químicos da Água/químicaRESUMO
Porcine circovirus 3 (PCV-3) prevalence has been minimally investigated in wild boar; dynamics of infection and viral tissue distribution are currently unknown. In this study, serum samples from 518 wild boar (from years 2004 to 2018) were used to study frequency of infection. Also, serum samples from 19 boar captured and recaptured at least two times for a period of time from 1 month to 1 year were collected to determine PCV-3 infection dynamics. Finally, to elucidate PCV-3 DNA organic distribution, sera, different tissues and faeces were obtained from 35 additional wild boar. PCV-3 DNA was extracted and amplified with a conventional PCR. For the PCV-3 PCR-positive sera from the longitudinally sampled and different tissue types, a quantitative PCR was performed. Genome sequence was obtained from a number of PCV-3 PCR-positive samples from different years, different time-points of infection and tissues. Obtained results confirmed the susceptibility of wild boar to the virus, showing high frequency of PCV-3 detection (221 out of 518, 42.66%) and demonstrating circulation at least since 2004. Compiled data indicate the possibility of long-term infections, since 5 out of 10 PCV-3 PCR-positive boars longitudinally sampled showed positivity in samplings separated for more than 5 months. All tested tissue types' harboured PCV-3 genome, with the highest percentage of PCR positivity in submandibular lymph node, tonsil, lung, liver, spleen and kidney. The amount of DNA in all tested PCV-3 PCR-positive samples was moderate to low. All partial and complete PCV-3 sequences obtained from wild boar displayed high nucleotide identity, higher than 98%. In conclusion, this study further confirms that wild boar is susceptible to PCV-3 infection, showing high frequency of detection in this animal species. Furthermore, PCV-3 can be found in different tissues of wild boar and is apparently able to cause persistent infection.
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Infecções por Circoviridae/veterinária , Circovirus/isolamento & purificação , Doenças dos Suínos/epidemiologia , Animais , Infecções por Circoviridae/sangue , Infecções por Circoviridae/epidemiologia , Infecções por Circoviridae/virologia , Feminino , Masculino , Reação em Cadeia da Polimerase/veterinária , Prevalência , Estudos Retrospectivos , Espanha/epidemiologia , Suínos , Doenças dos Suínos/sangue , Doenças dos Suínos/virologiaRESUMO
Tadalafil, a long-acting PED-5 inhibitor, is commonly used for the treatment of pulmonary arterial hypertension (PAH). However, its efficacy and clinical application are severely limited by the poor water solubility, low bioavailability and a series adverse effects (e.g. headaches, indigestion). In this study, tadalafil was prepared and loaded into biodegradable PLGA (poly(lactic-co-glycolic acid)) microspheres (TDF-PLGA-MS) via emulsification-solvent evaporation. The resulting microspheres were processed into pulmonary inhalant by freeze drying. The TDF-PLGA-MS was spherical and uniform, with an average particle diameter ~10.29 µm. The encapsulation efficiency and drug loading yield of TDF-PLGA-MS were 81.68% and 8.52%, respectively. The investigation of micromeritics showed that the TDF-PLGA-MS had low moisture content. The fluidity of powders was relatively good. The aerodynamic diameter and emptying rate of microspheres powders were 3.92 µm and 95.41%, respectively. Therefore, the microspheres powders were easy to be atomized, and can meet the requirements of pulmonary administration. In vitro release results showed that the microspheres group released slowly. The cumulative release in 24 h and 10 d was 46.87% and 84.06%, respectively. The in vitro release profile of TDF-PLGA-MS was in accordance with the Weibull model. The results of Pharmacokinetics showed that tadalafil from microspheres slowly released into the blood after intratracheal instillation. The pulmonary drug residue in 0.5 h was 3.5 times compared with solution group. The residual concentration in lung after 10d was still higher than that of solution group in 48 h. The t1/2β and MRT0-∞ were 3.10 times and 3.96 times that of solution group, respectively. Moreover, the Cmax and AUC of drug residues in lung were 3.48 times and 16.36 times that of solution group, respectively. The results of tissue distribution showed that the Re in lung was 16.358, which indicated the lung targeting. In conclusion, the TDF-PLGA-MS for pulmonary administration in this study can significantly improve the pulmonary targeting, increase efficacy of tadalafil and reduce other non-target organs toxicity. This study will have an important clinical significance for PAH patients who need long-term drug therapy.
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Farmacocinética , Tadalafila/efeitos adversos , Hipertensão Arterial Pulmonar/tratamento farmacológico , Microesferas , Pacientes/classificação , Solubilidade/efeitos dos fármacos , Técnicas In Vitro/instrumentação , Preparações Farmacêuticas/administração & dosagem , Tratamento Farmacológico , PulmãoRESUMO
Abstract A selective and sensitive liquid chromatography tandem with mass spectrometry was developed and validated for accurate determination of monotropein in rat plasma and tissues. All biological samples were prepared by simple protein precipitation method using catalpol as an internal standard. The analyte and internal standard were separated on a C18 analytical column with 2 min of run time, at flow rate of 0.5 ml/min. The detection was performed on a triple-quadrupole tandem mass spectrometer equipped with negative-ion electrospray ionization by selected-reaction monitoring of the transitions at m/z 389→147 for monotropein and m/z 361→169 for the internal standard. The calibration curves for plasma and tissue samples were linear over the concentration range of 4-2000 ng/ml, with a lower limit of quantification of 4 ng/ml. The method was successfully applied to a pharmacokinetic and tissue distribution study of monotropein in rats.
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For the first time, alcohol extracts of Atelopus hoogmoedi from the Guiana Shield in Suriname and Guyana were analyzed for the presence of tetrodotoxin (TTX) and of its analogues by high resolution hydrophilic interaction liquid chromatography/mass spectrometry. One specimen from Suriname was found to contain TTX and 4-epiTTX. Using a monoclonal antibody-based immunohistochemical staining technique, TTX was localized mainly in the granular glands and epithelium of the skin, but not in internal organs except liver showing weak TTX-positive reaction. In two specimens collected in Guyana, none of the toxins were detected.
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Bufonidae/fisiologia , Tetrodotoxina/metabolismo , Distribuição Animal , Animais , América do SulRESUMO
In the present work, we evaluated the effect of mixed Trypanosoma cruzi infections, studying the biological distribution of the different parasites in blood, heart and skeletal muscle during the acute phase. Albino Swiss mice were infected with different parasite strain/isolates or with a combination of them. The parasites in the different tissues were typified through specific PCR, population variability was analyzed through RFLP studies and parasitological and histopathological parameters were evaluated. We found a predominance of TcII and TcVI in all tissues samples respect to TcV and different parasite populations were found in circulation and in the tissues from the same host. These results verify the distribution of parasites in host tissues from early stages of infection and show biological interactions among different genotypes and populations of T. cruzi.
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Doença de Chagas/parasitologia , Trypanosoma cruzi/fisiologia , Animais , Doença de Chagas/sangue , Doença de Chagas/patologia , Feminino , Genótipo , Coração/parasitologia , Humanos , Masculino , Camundongos , Músculo Esquelético/parasitologia , Músculo Esquelético/patologia , Reação em Cadeia da Polimerase , Distribuição Tecidual , Trypanosoma cruzi/genética , Trypanosoma cruzi/crescimento & desenvolvimentoRESUMO
ABSTRACT A liquid chromatography-tandem mass spectrometry method was developed and validated for simultaneous determination of six bioactive constituents including vitexin, orientin, isoorientin, 2"-O-β-D-xylopyranosyl isoorientin, 2"-O-β-D-xylopyranosyl isovitexin, and 6-C-L-α-arabipyranosyl vitexin in rats' various tissues using isoquercitrin as the internal standard. Biological samples were pretreated by protein precipitation with acetonitrile. Chromatographic separation was carried out on a C18 column with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid. All analytes and internal standard were quantitated through electrospray ionization in negative ion selected reaction monitoring mode. The mass transitions were as follows: m/z 431 → 311 for vitexin, m/z 447 → 327 for orientin or isoorientin, m/z 579 → 459 for 2"-O-β-D-xylopyranosyl isoorientin, m/z 563 → 293 for 2"-O-β-D-xylopyranosyl isovitexin, m/z 563 → 353 for 6-C-L-α-arabipyranosyl vitexin, and m/z 463 → 300 for the internal standard, respectively. The lower limits of quantification for the six analytes in different tissue homogenates were 0.8-2.2 ng/ml. The validated assay was successfully applied to a tissue distribution study of the six components in rats after intravenous administration of total flavonoids of Scorzonera austriaca Willd; Asteraceae. The results of the tissue distribution study showed that the high concentrations of six components were mainly in the kidney.
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We determined the levels of Cd and Pb in liver and muscle of demersal fish from three lagoon systems (Urías, Huizache, and Teacapán) in the SE Gulf of California with the purpose of comparing the studied metals in fish from the three ecosystems and to assess the potential human health risk. Considering the number of individuals, the sequence of fish abundance was Teacapán > Huizache > Urías. Length and size at maturity of collected species showed that 76.5% of the individuals were juveniles. Overall, Cd and Pb were more accumulated in liver than in muscle. After multivariate analyses, considering fish tissue and locality, Cd and Pb levels were different (p < 0.05) between fish from Teacapán and Huizache. In general, the hazard quotients (HQs) of Pb were higher than the corresponding values of Cd; the highest HQ for Cd (0.0051) corresponded to Mugil curema, and the highest HQ for Pb (0.0099) was estimated in Diapterus peruvianus. With respect to the hazard index (accumulative risk from Cd and Pb), the most elevated value (HI = 0.0124) was estimated for Pomadasys macracanthus. Estimated HI does not represent a health risk at the consumption rates of the Mexican population.
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Cádmio , Chumbo , Animais , California , Monitoramento Ambiental , Peixes , Humanos , Metais Pesados , México , Medição de Risco , Poluentes Químicos da ÁguaRESUMO
The aim of the present study was to evaluate the accumulation of cypermethrin and chlorpyrifos when the fish Jenynsia multidentata was exposed to these pesticides singly and in technical and commercial mixtures. Adult female fish were exposed over 96 h to 0.04 µg/L of cypermethrin; 0.4 µg/L of chlorpyrifos; 0.04 µg/L of cypermethrin + 0.4 µg/L of chlorpyrifos in a technical mixture; and 0.04 µg/L of cypermethrin + 0.4 µg/L of chlorpyrifos in a mixture of commercial products. Fish exposed to cypermethrin accumulated this compound only in muscle, probably because of the low biotransformation capacity of this organ and the induction of cytochrome P4501A1 (CYP1A1) expression in the liver. The accumulation of chlorpyrifos occurred in fish exposed to the insecticide (intestine > liver > gills) even when these fish had higher gluthatione-S-transferase (GST) activity in gills and P-glycoprotein (P-gp) expression in the liver, compared with the control. Fish exposed to the technical mixture showed cypermethrin accumulation (liver > intestine > gills) with higher levels than those measured in fish after only cypermethrin exposure. Higher expression levels of CYP1A1 in the liver were also observed compared with the Control. Fish exposed to the commercial mixture accumulated both insecticides (cypermethrin: intestine > gills and chlorpyrifos: liver > intestine > gills > muscle). In the organs where accumulation occurred, biotransformation enzymes were inhibited. Consequently, the commercial formulation exposure provoked the highest accumulation of cypermethrin and chlorpyrifos in J. multidentata, possibly associated with the biotransformation system inhibition. Environ Toxicol Chem 2017;36:1764-1774. © 2016 SETAC.
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Clorpirifos/metabolismo , Ciprinodontiformes/metabolismo , Inseticidas/metabolismo , Piretrinas/metabolismo , Poluentes Químicos da Água/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Biotransformação , Clorpirifos/análise , Clorpirifos/toxicidade , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP1A1/metabolismo , Feminino , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Glutationa Transferase/metabolismo , Inseticidas/análise , Inseticidas/química , Inseticidas/toxicidade , Mucosa Intestinal/metabolismo , Intestinos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Músculos/efeitos dos fármacos , Músculos/metabolismo , Piretrinas/análise , Piretrinas/toxicidade , Espectrometria de Massas por Ionização por Electrospray , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
BACKGROUND: Vitamin A (VA; retinol) supplementation is recommended for children aged >6 mo in countries with high rates of malnutrition, but the distribution and retention of VA in body tissues have not been extensively explored. OBJECTIVE: We sought to determine the distribution and retention of VA in tissues of neonatal rats raised under VA-marginal conditions. METHODS: Sprague-Dawley neonatal rats (n = 104; 63 males) nursed by mothers fed a VA-marginal diet (0.35 mg retinol equivalents/kg diet) were randomized and treated on postnatal day 4 with an oral dose of either VA (6 µg retinyl palmitate/g body weight) or canola oil as control. Pups (n = 4/group) were killed at 13 time points from 30 min to 24 d after dose administration. The total retinol concentration and mass were determined in all collected organs. RESULTS: In the control group, plasma VA was marginal (0.8 µmol/L), whereas liver VA was deficient (<70 nmol/g). Nonetheless, the liver contained most (â¼76%) of the total VA mass in the body, whereas extrahepatic nondigestive organs together contained â¼13%. White adipose tissue (WAT), which was nearly absent before postnatal day 12, contained only â¼1%. In VA-supplemented neonates, the mean total retinol concentrations in all organs were significantly greater than in control pups. However, this increase lasted for only â¼1 d in most extrahepatic tissues, with the exception of WAT, in which it lasted 18 d. CONCLUSIONS: Extrahepatic organs in neonatal rats raised under VA-marginal conditions store relatively little VA, and the scarcity of adipose tissue may predispose neonates to a low-VA status. The effect of VA supplementation on VA content in most extrahepatic organs is transient. A more frequent supplementation along with other nutritional interventions may be necessary for maintaining a steady supply of retinol to the rapidly developing extrahepatic organs.
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Suplementos Nutricionais , Vitamina A/administração & dosagem , Vitamina A/sangue , Tecido Adiposo Branco/metabolismo , Animais , Animais Recém-Nascidos , Peso Corporal , Dieta , Diterpenos , Relação Dose-Resposta a Droga , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Óleos de Plantas/administração & dosagem , Distribuição Aleatória , Óleo de Brassica napus , Ratos , Ratos Sprague-Dawley , Ésteres de Retinil , Vitamina A/análogos & derivadosRESUMO
Ivermectin (IVM) is probably one of the most widely used antiparasitic drugs worldwide, and its efficacy is well established. However, slight differences in formulation may change the plasma kinetics, the biodistribution, and in consequence, the efficacy of this compound. The present study focuses on the development of a novel nanocarrier for the delivery of lipophilic drugs such as IVM and its potential application in antiparasitic control. Lipid nanocapsules (LNC) were prepared by a new phase inversion procedure and characterized in terms of size, surface potential, encapsulation efficiency, and physical stability. A complement activation assay (CH50) and uptake experiments by THP-1 macrophage cells were used to assess the stealth properties of this nanocarrier in vitro. Finally, a pharmacokinetics and biodistribution study was carried out as a proof of concept after subcutaneous (SC) injection in a rat model. The final IVM-LNC suspension displayed a narrow size distribution and an encapsulation rate higher than 90 % constant over the evaluated time (60 days). Through flow cytometry and blood permanence measurements, it was possible to confirm the ability of these particles to avoid the macrophage uptake. Moreover, the systemic disposition of IVM in the LNC administered by the SC route was higher (p < 0.05) (1367 ng h/ml) compared to treatment with a commercial formulation (CF) (1193 ng.h/ml), but no significant differences in the biodistribution pattern were found. In conclusion, this new carrier seems to be a promising therapeutic approach in antiparasitic control and to delay the appearance of resistance.
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Antiparasitários/uso terapêutico , Ivermectina/administração & dosagem , Lipídeos/química , Nanocápsulas/química , Animais , Vias de Administração de Medicamentos , Portadores de Fármacos , Injeções Subcutâneas , Ivermectina/sangue , Ivermectina/farmacocinética , Macrófagos/metabolismo , Ratos , Distribuição TecidualRESUMO
This study investigates the occurrence of diarrhetic shellfish toxins (DSTs) and their producing phytoplankton species in southern Brazil, as well as the potential for toxin accumulation in co-occurring mussels (Perna perna) and octopuses (Octopus vulgaris). During the spring in 2012 and 2013, cells of Dinophysis acuminata complex were always present, sometimes at relatively high abundances (max. 1143 cells L-1), likely the main source of okadaic acid (OA) in the plankton (max. 34 ng L-1). Dinophysis caudata occurred at lower cell densities in 2013 when the lipophilic toxins pectenotoxin-2 (PTX-2) and PTX-2 seco acid were detected in plankton and mussel samples. Here, we report for the first time the accumulation of DSTs in octopuses, probably linked to the consumption of contaminated bivalves. Perna perna mussels were consistently contaminated with different DSTs (max. 42 µg kg-1), and all octopuses analyzed (n = 5) accumulated OA in different organs/tissues: digestive glands (DGs) > arms > gills > kidneys > stomach + intestine. Additionally, similar concentrations of 7-O-palmytoyl OA and 7-O-palmytoly dinophysistoxin-1 (DTX-1) were frequently detected in the hepatopancreas of P. perna and DGs of O. vulgaris. Therefore, octopuses can be considered a potential vector of DSTs to both humans and top predators such as marine mammals.
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Bivalves/química , Toxinas Marinhas/análise , Octopodiformes/química , Ácido Okadáico/análise , Animais , Brasil , Dinoflagellida/química , Estuários , Proliferação Nociva de Algas/fisiologia , Humanos , Toxinas Marinhas/química , Ácido Okadáico/química , Fitoplâncton/química , Intoxicação por Frutos do Mar/prevenção & controleRESUMO
The aim of the present study was to investigate the tissue distribution and excretion of five components of Portulaca oleracea L. extract (POE) in rat following oral administration. A rapid, sensitive and specific ultra-high performance liquid chromatography (UHPLC) method with puerarin as the internal standard was used for the quantitative analysis of five components of POE, including caffeic acid (CA), p-coumaric acid (p-CA), ferulic acid (FA), quercitrin (QUER) and hesperidin (HP) in rat tissues including the liver, intestine, stomach, muscle, heart, lung, brain, kidney and spleen, urine and feces. The results show that onlyp-CA and FA were found in nearly all tissues with low cumulative ratios, and CA was higher in the intestine and stomach with a slightly higher cumulative ratio in the urine and feces after 24 h. HP and QUER were found at low levels in the tissues with low cumulative ratios.
O objetivo do presente estudo foi investigar a distribuição tecidual e excreção de cinco componentes de extrato Portulaca oleracea L. (POE) em ratos após administração oral. Um método analítico rápido, sensível e específico para quantificação de cinco componentes de POE (ácido cafeico (CA), ácidop-cumárico (p-CA), ácido ferúlico (FA), quercitrina (QUER) e hesperidina (HP)) por cromatografia líquida de ultra eficiência (UHPLC), empregando puerarina como padrão interno de referência. Os compostos foram quantificados em diferentes tecidos dos animais, sendo eles fígado, intestino, estômago, músculo, coração, pulmão, cérebro, rim e baço, urina e fezes. Os resultados mostraram que apenas p-CA e FA foram encontradas em todos os tecidos com baixas taxas cumulativas e CA apresentou níveis mais altos no intestino e estômago com a taxa cumulativa um pouco mais elevada na urina e nas fezes após 24 h. HP e QUER apresentaram baixas concentrações nos tecidos com baixas taxas cumulativas.